Prodrugs are pharmacologically inactive derivatives of active drug molecules that are designed to overcome barriers to the optimal performance of the parent drug and are biotransformed in the body into the active drug. Common functional groups used in prodrug design include carboxylic acids, alcohols, amines, phosphates and carbonyls. Prodrugs are typically produced by modifying these groups, such as through esterification, to form esters, carbonates, carbamates, amides and phosphates. Upon administration, prodrugs are enzymatically or chemically transformed back into the active drug molecule.

1. Prodrugs
Aman Kumar Naik
Integrated M.Sc.9/11/2015 :: National Institute of Science Education and Research ::

2. OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
Carbamates
O
NHR
Amides
N
H
O P
O
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
–PO(OH)2
–SH
–COOH
–NH
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the disease s
dose and the duration of therapy.
• Parent and prodrug: the absorption, distribut
metabolism, excretion (ADME) and pharmacokin
properties need to be comprehensively understo
• Degradation by-products: these can affect chem
and physical stability and lead to the formatio
new degradation products.
Some of the most common functional groups tha
amenable to prodrug design include carboxylic, hydro
amine, phosphate/phosphonate and carbonyl gro
Prodrugs typically produced via the modification of t
groups include esters, carbonates, carbamates, ami
phosphates and oximes. However, other uncomm
functional groups have also been investigated as po
tially useful structures in prodrug design. For exam
thiols react in a similar manner to alcohols and ca
derivatized to thioethers18
and thioesters19
. Amines
bederivatizedintoimines20,21
andN-Mannichbases22
.
prodrug structures for the most common functional
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol fu
tionalities. Esters are the most common prodrugs u
anditisestimatedthatapproximately49%ofallmark
prodrugs are activated by enzymatic hydrolysis4
. E
prodrugs are most often used to enhance the lipophili
REVIEWS
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
Carbamates
O
NHR
Amides
N
H
O P
O
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
–PO(OH)2
–SH
–COOH
–NH
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the disease s
dose and the duration of therapy.
• Parent and prodrug: the absorption, distribut
metabolism, excretion (ADME) and pharmacokin
properties need to be comprehensively understo
• Degradation by-products: these can affect chem
and physical stability and lead to the formatio
new degradation products.
Some of the most common functional groups tha
amenable to prodrug design include carboxylic, hydro
amine, phosphate/phosphonate and carbonyl gro
Prodrugs typically produced via the modification of t
groups include esters, carbonates, carbamates, ami
phosphates and oximes. However, other uncomm
functional groups have also been investigated as po
tially useful structures in prodrug design. For exam
thiols react in a similar manner to alcohols and ca
derivatized to thioethers18
and thioesters19
. Amines
bederivatizedintoimines20,21
andN-Mannichbases22
.
prodrug structures for the most common functional
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol fu
tionalities. Esters are the most common prodrugs u
anditisestimatedthatapproximately49%ofallmark
prodrugs are activated by enzymatic hydrolysis4
. E
prodrugs are most often used to enhance the lipophili
REVIEWS
Enzymatic and/or chemical transformation
Representative illustration of the prodrug concept
Pharmacologically inactive
Pharmacologically active
Covalently linked via bioreversible groups that are chemically or enzymatically labile
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
–PO(OH)2
–SH
–COOH
–NH
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the disease state,
dose and the duration of therapy.
• Parent and prodrug: the absorption, distribution,
metabolism, excretion (ADME) and pharmacokinetic
properties need to be comprehensively understood.
• Degradation by-products: these can affect chemical
and physical stability and lead to the formation of
new degradation products.
Some of the most common functional groups that are
amenable to prodrug design include carboxylic, hydroxyl,
amine, phosphate/phosphonate and carbonyl groups.
Prodrugs typically produced via the modification of these
groups include esters, carbonates, carbamates, amides,
phosphates and oximes. However, other uncommon
functional groups have also been investigated as poten-
tially useful structures in prodrug design. For example,
thiols react in a similar manner to alcohols and can be
derivatized to thioethers18
and thioesters19
. Amines may
bederivatizedintoimines20,21
andN-Mannichbases22
.The
prodrug structures for the most common functionalities
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol func-
tionalities. Esters are the most common prodrugs used,
anditisestimatedthatapproximately49%ofallmarketed
prodrugs are activated by enzymatic hydrolysis4
. Ester
prodrugs are most often used to enhance the lipophilicity,
and thus the passive membrane permeability, of water-
soluble drugs by masking charged groups such as car-
REVIEWS
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
–PO(OH)2
–SH
–COOH
–NH
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with
dose and the duration of t
• Parent and prodrug: the
metabolism, excretion (AD
properties need to be com
• Degradation by-products
and physical stability and
new degradation products
Some of the most common
amenable to prodrug design in
amine, phosphate/phosphon
Prodrugs typically produced v
groups include esters, carbon
phosphates and oximes. Ho
functional groups have also b
tially useful structures in pro
thiols react in a similar mann
derivatized to thioethers18
and
bederivatizedintoimines20,21
a
prodrug structures for the mo
are illustrated in FIG. 1b and di
Esters as prodrugs of carboxy
tionalities. Esters are the mos
anditisestimatedthatapproxi
prodrugs are activated by en
prodrugs are most often used t
and thus the passive membra
soluble drugs by masking ch
REVIEWS
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
–PO(OH)2
–SH
–COOH
–NH
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the disease
dose and the duration of therapy.
• Parent and prodrug: the absorption, distribu
metabolism, excretion (ADME) and pharmacoki
properties need to be comprehensively underst
• Degradation by-products: these can affect chem
and physical stability and lead to the formatio
new degradation products.
Some of the most common functional groups th
amenable to prodrug design include carboxylic, hydr
amine, phosphate/phosphonate and carbonyl gro
Prodrugs typically produced via the modification of
groups include esters, carbonates, carbamates, am
phosphates and oximes. However, other uncom
functional groups have also been investigated as p
tially useful structures in prodrug design. For exam
thiols react in a similar manner to alcohols and ca
derivatized to thioethers18
and thioesters19
. Amines
bederivatizedintoimines20,21
andN-Mannichbases22
prodrug structures for the most common functiona
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol
tionalities. Esters are the most common prodrugs
anditisestimatedthatapproximately49%ofallmark
prodrugs are activated by enzymatic hydrolysis4
.
prodrugs are most often used to enhance the lipophi
and thus the passive membrane permeability, of w
soluble drugs by masking charged groups such as
REVIEWS

3. Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the disease state,
dose and the duration of therapy.
• Parent and prodrug: the absorption, distribution,
metabolism, excretion (ADME) and pharmacokinetic
properties need to be comprehensively understood.
• Degradation by-products: these can affect chemical
and physical stability and lead to the formation of
new degradation products.
Some of the most common functional groups that are
amenable to prodrug design include carboxylic, hydroxyl,
amine, phosphate/phosphonate and carbonyl groups.
Prodrugs typically produced via the modification of these
groups include esters, carbonates, carbamates, amides,
phosphates and oximes. However, other uncommon
functional groups have also been investigated as poten-
tially useful structures in prodrug design. For example,
thiols react in a similar manner to alcohols and can be
derivatized to thioethers18
and thioesters19
. Amines may
bederivatizedintoimines20,21
andN-Mannichbases22
.The
prodrug structures for the most common functionalities
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol func-
tionalities. Esters are the most common prodrugs used,
anditisestimatedthatapproximately49%ofallmarketed
prodrugs are activated by enzymatic hydrolysis4
. Ester
prodrugs are most often used to enhance the lipophilicity,
and thus the passive membrane permeability, of water-
soluble drugs by masking charged groups such as car-
boxylic acids and phosphates3,23
. The synthesis of an ester
prodrug is often straightforward. Once in the body, the
ester bond is readily hydrolysed by ubiquitous esterases
found in the blood, liver and other organs and tissues24
,
including carboxylesterases, acetylcholinesterases,
butyrylcholinesterases, paraoxonases and arylesterases.
However, one significant challenge with ester prodrugs is
the accurate prediction of pharmacokinetic disposition
in humans, owing to significant differences in specific
carboxylesterase activities in preclinical species25
, as
reported for the exploratory intravenous diester pro-
drug of nalbuphine26
. A comprehensive review on ester
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug +
Barrier
b
Promoiety Promoiety and physical stability and lead to the formation of
new degradation products.
Some of the most common functional groups that are
amenable to prodrug design include carboxylic, hydroxyl,
amine, phosphate/phosphonate and carbonyl groups.
Prodrugs typically produced via the modification of these
groups include esters, carbonates, carbamates, amides,
phosphates and oximes. However, other uncommon
functional groups have also been investigated as poten-
tially useful structures in prodrug design. For example,
thiols react in a similar manner to alcohols and can be
derivatized to thioethers18
and thioesters19
. Amines may
bederivatizedintoimines20,21
andN-Mannichbases22
.The
prodrug structures for the most common functionalities
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol func-
tionalities. Esters are the most common prodrugs used,
anditisestimatedthatapproximately49%ofallmarketed
prodrugs are activated by enzymatic hydrolysis4
. Ester
prodrugs are most often used to enhance the lipophilicity,
and thus the passive membrane permeability, of water-
soluble drugs by masking charged groups such as car-
boxylic acids and phosphates3,23
. The synthesis of an ester
prodrug is often straightforward. Once in the body, the
ester bond is readily hydrolysed by ubiquitous esterases
found in the blood, liver and other organs and tissues24
,
including carboxylesterases, acetylcholinesterases,
butyrylcholinesterases, paraoxonases and arylesterases.
However, one significant challenge with ester prodrugs is
the accurate prediction of pharmacokinetic disposition
in humans, owing to significant differences in specific
carboxylesterase activities in preclinical species25
, as
reported for the exploratory intravenous diester pro-
drug of nalbuphine26
. A comprehensive review on ester
prodrugs that enhance oral absorption of predominantly
poorly permeable and polar parent drugs was recently
published by Beaumont et al.3
Several alkyl and aryl ester prodrugs are in clinical
use3
, of which angiotensin-converting enzyme (ACE)
24
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
are covalently linked via bioreversible groups that are chemically or enzymatically labile,
such as those shown here. The ‘ideal’ prodrug yields the parent drug with high recovery
ratios, with the promoiety being non-toxic. b | Common functional groups on parent
drugs that are amenable to prodrug design (shown in green). Most prodrug approaches
require a ‘synthetic handle’ on the drug, which are typically heteroatomic groups.
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the disease stat
dose and the duration of therapy.
• Parent and prodrug: the absorption, distributio
metabolism, excretion (ADME) and pharmacokinet
properties need to be comprehensively understood
• Degradation by-products: these can affect chemic
and physical stability and lead to the formation
new degradation products.
Some of the most common functional groups that a
amenable to prodrug design include carboxylic, hydrox
amine, phosphate/phosphonate and carbonyl group
Prodrugs typically produced via the modification of the
groups include esters, carbonates, carbamates, amide
phosphates and oximes. However, other uncommo
functional groups have also been investigated as pote
tially useful structures in prodrug design. For examp
thiols react in a similar manner to alcohols and can b
derivatized to thioethers18
and thioesters19
. Amines m
bederivatizedintoimines20,21
andN-Mannichbases22
.Th
prodrug structures for the most common functionaliti
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol fun
tionalities. Esters are the most common prodrugs use
anditisestimatedthatapproximately49%ofallmarkete
prodrugs are activated by enzymatic hydrolysis4
. Est
prodrugs are most often used to enhance the lipophilici
and thus the passive membrane permeability, of wate
soluble drugs by masking charged groups such as ca
boxylic acids and phosphates3,23
. The synthesis of an est
prodrug is often straightforward. Once in the body, th
ester bond is readily hydrolysed by ubiquitous esteras
found in the blood, liver and other organs and tissues
including carboxylesterases, acetylcholinesterase
butyrylcholinesterases, paraoxonases and arylesterase
However, one significant challenge with ester prodrugs
the accurate prediction of pharmacokinetic dispositio
in humans, owing to significant differences in specif
carboxylesterase activities in preclinical species25
,
reported for the exploratory intravenous diester pr
drug of nalbuphine26
. A comprehensive review on est
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug
Drug
+
and/or chemical
transformation
Barrier
b
Promoiety Promoiety
• Parent and prodrug: the absorption, distribution,
metabolism, excretion (ADME) and pharmacokinetic
properties need to be comprehensively understood.
• Degradation by-products: these can affect chemical
and physical stability and lead to the formation of
new degradation products.
Some of the most common functional groups that are
amenable to prodrug design include carboxylic, hydroxyl,
amine, phosphate/phosphonate and carbonyl groups.
Prodrugs typically produced via the modification of these
groups include esters, carbonates, carbamates, amides,
phosphates and oximes. However, other uncommon
functional groups have also been investigated as poten-
tially useful structures in prodrug design. For example,
thiols react in a similar manner to alcohols and can be
derivatized to thioethers18
and thioesters19
. Amines may
bederivatizedintoimines20,21
andN-Mannichbases22
.The
prodrug structures for the most common functionalities
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol func-
tionalities. Esters are the most common prodrugs used,
anditisestimatedthatapproximately49%ofallmarketed
prodrugs are activated by enzymatic hydrolysis4
. Ester
prodrugs are most often used to enhance the lipophilicity,
and thus the passive membrane permeability, of water-
soluble drugs by masking charged groups such as car-
boxylic acids and phosphates3,23
. The synthesis of an ester
prodrug is often straightforward. Once in the body, the
ester bond is readily hydrolysed by ubiquitous esterases
found in the blood, liver and other organs and tissues24
,
including carboxylesterases, acetylcholinesterases,
butyrylcholinesterases, paraoxonases and arylesterases.
However, one significant challenge with ester prodrugs is
the accurate prediction of pharmacokinetic disposition
in humans, owing to significant differences in specific
carboxylesterase activities in preclinical species25
, as
reported for the exploratory intravenous diester pro-
drug of nalbuphine26
. A comprehensive review on ester
prodrugs that enhance oral absorption of predominantly
poorly permeable and polar parent drugs was recently
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
are covalently linked via bioreversible groups that are chemically or enzymatically labile,
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug +
Barrier
b
Promoiety Promoiety
• Degradation by-products: these can affect chemical
and physical stability and lead to the formation of
new degradation products.
Some of the most common functional groups that are
amenable to prodrug design include carboxylic, hydroxyl,
amine, phosphate/phosphonate and carbonyl groups.
Prodrugs typically produced via the modification of these
groups include esters, carbonates, carbamates, amides,
phosphates and oximes. However, other uncommon
functional groups have also been investigated as poten-
tially useful structures in prodrug design. For example,
thiols react in a similar manner to alcohols and can be
derivatized to thioethers18
and thioesters19
. Amines may
bederivatizedintoimines20,21
andN-Mannichbases22
.The
prodrug structures for the most common functionalities
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol func-
tionalities. Esters are the most common prodrugs used,
anditisestimatedthatapproximately49%ofallmarketed
prodrugs are activated by enzymatic hydrolysis4
. Ester
prodrugs are most often used to enhance the lipophilicity,
and thus the passive membrane permeability, of water-
soluble drugs by masking charged groups such as car-
boxylic acids and phosphates3,23
. The synthesis of an ester
prodrug is often straightforward. Once in the body, the
ester bond is readily hydrolysed by ubiquitous esterases
found in the blood, liver and other organs and tissues24
,
including carboxylesterases, acetylcholinesterases,
butyrylcholinesterases, paraoxonases and arylesterases.
However, one significant challenge with ester prodrugs is
the accurate prediction of pharmacokinetic disposition
in humans, owing to significant differences in specific
carboxylesterase activities in preclinical species25
, as
reported for the exploratory intravenous diester pro-
drug of nalbuphine26
. A comprehensive review on ester
prodrugs that enhance oral absorption of predominantly
poorly permeable and polar parent drugs was recently
published by Beaumont et al.3
Several alkyl and aryl ester prodrugs are in clinical
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
are covalently linked via bioreversible groups that are chemically or enzymatically labile,
such as those shown here. The ‘ideal’ prodrug yields the parent drug with high recovery
ratios, with the promoiety being non-toxic. b | Common functional groups on parent
drugs that are amenable to prodrug design (shown in green). Most prodrug approachesNature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the dise
dose and the duration of therapy.
• Parent and prodrug: the absorption, distr
metabolism, excretion (ADME) and pharma
properties need to be comprehensively und
• Degradation by-products: these can affect
and physical stability and lead to the form
new degradation products.
Some of the most common functional group
amenable to prodrug design include carboxylic,
amine, phosphate/phosphonate and carbony
Prodrugs typically produced via the modification
groups include esters, carbonates, carbamates
phosphates and oximes. However, other unc
functional groups have also been investigated a
tially useful structures in prodrug design. For
thiols react in a similar manner to alcohols an
derivatized to thioethers18
and thioesters19
. Am
bederivatizedintoimines20,21
andN-Mannichba
prodrug structures for the most common funct
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and th
tionalities. Esters are the most common prodru
anditisestimatedthatapproximately49%ofallm
prodrugs are activated by enzymatic hydrolys
prodrugs are most often used to enhance the lipo
and thus the passive membrane permeability,
soluble drugs by masking charged groups suc
boxylic acids and phosphates3,23
. The synthesis o
prodrug is often straightforward. Once in the b
ester bond is readily hydrolysed by ubiquitous
found in the blood, liver and other organs and
including carboxylesterases, acetylcholine
butyrylcholinesterases, paraoxonases and aryle
However, one significant challenge with ester pr
the accurate prediction of pharmacokinetic di
in humans, owing to significant differences in
carboxylesterase activities in preclinical spe
reported for the exploratory intravenous die
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
b
Promoiety Promoiety
dose and the duration of therapy.
• Parent and prodrug: the absorption, distr
metabolism, excretion (ADME) and pharmac
properties need to be comprehensively unde
• Degradation by-products: these can affect c
and physical stability and lead to the form
new degradation products.
Some of the most common functional group
amenable to prodrug design include carboxylic, h
amine, phosphate/phosphonate and carbonyl
Prodrugs typically produced via the modification
groups include esters, carbonates, carbamates,
phosphates and oximes. However, other unc
functional groups have also been investigated a
tially useful structures in prodrug design. For e
thiols react in a similar manner to alcohols an
derivatized to thioethers18
and thioesters19
. Ami
bederivatizedintoimines20,21
andN-Mannichbas
prodrug structures for the most common functi
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and th
tionalities. Esters are the most common prodru
anditisestimatedthatapproximately49%ofallm
prodrugs are activated by enzymatic hydrolys
prodrugs are most often used to enhance the lipo
and thus the passive membrane permeability, o
soluble drugs by masking charged groups suc
boxylic acids and phosphates3,23
. The synthesis o
prodrug is often straightforward. Once in the b
ester bond is readily hydrolysed by ubiquitous
found in the blood, liver and other organs and
including carboxylesterases, acetylcholines
butyrylcholinesterases, paraoxonases and aryle
However, one significant challenge with ester pro
the accurate prediction of pharmacokinetic dis
in humans, owing to significant differences in
carboxylesterase activities in preclinical spec
reported for the exploratory intravenous dies
drug of nalbuphine26
. A comprehensive review
prodrugs that enhance oral absorption of predom
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug +
transformation
Barrier
b
Promoiety Promoiety
metabolism, excretion (ADME) and pharmac
properties need to be comprehensively unde
• Degradation by-products: these can affect c
and physical stability and lead to the form
new degradation products.
Some of the most common functional groups
amenable to prodrug design include carboxylic, h
amine, phosphate/phosphonate and carbonyl
Prodrugs typically produced via the modification
groups include esters, carbonates, carbamates,
phosphates and oximes. However, other unc
functional groups have also been investigated a
tially useful structures in prodrug design. For e
thiols react in a similar manner to alcohols an
derivatized to thioethers18
and thioesters19
. Ami
bederivatizedintoimines20,21
andN-Mannichbas
prodrug structures for the most common functi
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and th
tionalities. Esters are the most common prodru
anditisestimatedthatapproximately49%ofallm
prodrugs are activated by enzymatic hydrolysi
prodrugs are most often used to enhance the lipo
and thus the passive membrane permeability, o
soluble drugs by masking charged groups such
boxylic acids and phosphates3,23
. The synthesis o
prodrug is often straightforward. Once in the b
ester bond is readily hydrolysed by ubiquitous e
found in the blood, liver and other organs and
including carboxylesterases, acetylcholines
butyrylcholinesterases, paraoxonases and aryle
However, one significant challenge with ester pro
the accurate prediction of pharmacokinetic dis
in humans, owing to significant differences in
carboxylesterase activities in preclinical spec
reported for the exploratory intravenous dies
drug of nalbuphine26
. A comprehensive review
prodrugs that enhance oral absorption of predom
poorly permeable and polar parent drugs was
published by Beaumont et al.3
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
are covalently linked via bioreversible groups that are chemically or enzymatically labile,
such as those shown here. The ‘ideal’ prodrug yields the parent drug with high recovery
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Barrier
b
new degradation products.
Some of the most common functional group
amenable to prodrug design include carboxylic, h
amine, phosphate/phosphonate and carbonyl
Prodrugs typically produced via the modification
groups include esters, carbonates, carbamates,
phosphates and oximes. However, other unc
functional groups have also been investigated a
tially useful structures in prodrug design. For e
thiols react in a similar manner to alcohols an
derivatized to thioethers18
and thioesters19
. Am
bederivatizedintoimines20,21
andN-Mannichbas
prodrug structures for the most common functi
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and th
tionalities. Esters are the most common prodru
anditisestimatedthatapproximately49%ofallm
prodrugs are activated by enzymatic hydrolys
prodrugs are most often used to enhance the lipo
and thus the passive membrane permeability, o
soluble drugs by masking charged groups suc
boxylic acids and phosphates3,23
. The synthesis o
prodrug is often straightforward. Once in the b
ester bond is readily hydrolysed by ubiquitous
found in the blood, liver and other organs and
including carboxylesterases, acetylcholines
butyrylcholinesterases, paraoxonases and aryle
However, one significant challenge with ester pro
the accurate prediction of pharmacokinetic dis
in humans, owing to significant differences in
carboxylesterase activities in preclinical spe
reported for the exploratory intravenous dies
drug of nalbuphine26
. A comprehensive review
prodrugs that enhance oral absorption of predom
poorly permeable and polar parent drugs was
published by Beaumont et al.3
Several alkyl and aryl ester prodrugs are in
use3
, of which angiotensin-converting enzym
inhibitors are some of the most successful2
representative sample shown in TABLE 1. How
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
are covalently linked via bioreversible groups that are chemically or enzymatically labile,
such as those shown here. The ‘ideal’ prodrug yields the parent drug with high recovery
ratios, with the promoiety being non-toxic. b | Common functional groups on parent
drugs that are amenable to prodrug design (shown in green). Most prodrug approaches
require a ‘synthetic handle’ on the drug, which are typically heteroatomic groups.
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the disease s
dose and the duration of therapy.
• Parent and prodrug: the absorption, distribut
metabolism, excretion (ADME) and pharmacokin
properties need to be comprehensively understo
• Degradation by-products: these can affect chem
and physical stability and lead to the formatio
new degradation products.
Some of the most common functional groups tha
amenable to prodrug design include carboxylic, hydro
amine, phosphate/phosphonate and carbonyl gro
Prodrugs typically produced via the modification of t
groups include esters, carbonates, carbamates, ami
phosphates and oximes. However, other uncomm
functional groups have also been investigated as po
tially useful structures in prodrug design. For exam
thiols react in a similar manner to alcohols and ca
derivatized to thioethers18
and thioesters19
. Amines
bederivatizedintoimines20,21
andN-Mannichbases22
.
prodrug structures for the most common functional
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol fu
tionalities. Esters are the most common prodrugs u
anditisestimatedthatapproximately49%ofallmark
prodrugs are activated by enzymatic hydrolysis4
. E
prodrugs are most often used to enhance the lipophili
and thus the passive membrane permeability, of wa
soluble drugs by masking charged groups such as
boxylic acids and phosphates3,23
. The synthesis of an e
prodrug is often straightforward. Once in the body
ester bond is readily hydrolysed by ubiquitous ester
found in the blood, liver and other organs and tissu
including carboxylesterases, acetylcholinestera
butyrylcholinesterases, paraoxonases and arylestera
However, one significant challenge with ester prodru
the accurate prediction of pharmacokinetic disposi
REVIEWS
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Barrier
b
new degradation products.
Some of the most common funct
amenable to prodrug design include
amine, phosphate/phosphonate an
Prodrugs typically produced via the m
groups include esters, carbonates, c
phosphates and oximes. However
functional groups have also been in
tially useful structures in prodrug d
thiols react in a similar manner to
derivatized to thioethers18
and thioe
bederivatizedintoimines20,21
andN-M
prodrug structures for the most com
are illustrated in FIG. 1b and discusse
Esters as prodrugs of carboxyl, hydr
tionalities. Esters are the most com
anditisestimatedthatapproximately
prodrugs are activated by enzymat
prodrugs are most often used to enha
and thus the passive membrane pe
soluble drugs by masking charged
boxylic acids and phosphates3,23
. The
prodrug is often straightforward. O
ester bond is readily hydrolysed by
found in the blood, liver and other
including carboxylesterases, ace
butyrylcholinesterases, paraoxonas
However, one significant challenge w
the accurate prediction of pharmac
in humans, owing to significant di
carboxylesterase activities in prec
reported for the exploratory intra
drug of nalbuphine26
. A comprehen
prodrugs that enhance oral absorpti
poorly permeable and polar paren
published by Beaumont et al.3
Several alkyl and aryl ester pro
use3
, of which angiotensin-conver
inhibitors are some of the most
representative sample shown in TA
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
are covalently linked via bioreversible groups that are chemically or enzymatically labile,
such as those shown here. The ‘ideal’ prodrug yields the parent drug with high recovery
ratios, with the promoiety being non-toxic. b | Common functional groups on parent
drugs that are amenable to prodrug design (shown in green). Most prodrug approaches
require a ‘synthetic handle’ on the drug, which are typically heteroatomic groups.
Nature Reviews | Drug Discovery
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug +
Barrier
b
Promoiety Promoiety
• Degradation by-products: th
and physical stability and le
new degradation products.
Some of the most common fu
amenable to prodrug design inclu
amine, phosphate/phosphonate
Prodrugs typically produced via th
groups include esters, carbonate
phosphates and oximes. Howe
functional groups have also been
tially useful structures in prodru
thiols react in a similar manner
derivatized to thioethers18
and th
bederivatizedintoimines20,21
and
prodrug structures for the most c
are illustrated in FIG. 1b and discu
Esters as prodrugs of carboxyl, h
tionalities. Esters are the most co
anditisestimatedthatapproxima
prodrugs are activated by enzym
prodrugs are most often used to e
and thus the passive membrane
soluble drugs by masking charg
boxylic acids and phosphates3,23
. T
prodrug is often straightforward
ester bond is readily hydrolysed
found in the blood, liver and oth
including carboxylesterases, a
butyrylcholinesterases, paraoxon
However, one significant challeng
the accurate prediction of pharm
in humans, owing to significant
carboxylesterase activities in p
reported for the exploratory in
drug of nalbuphine26
. A compreh
prodrugs that enhance oral absor
poorly permeable and polar par
published by Beaumont et al.3
Several alkyl and aryl ester p
use3
, of which angiotensin-conv
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
In broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
are covalently linked via bioreversible groups that are chemically or enzymatically labile,
such as those shown here. The ‘ideal’ prodrug yields the parent drug with high recovery
ratios, with the promoiety being non-toxic. b | Common functional groups on parent
drugs that are amenable to prodrug design (shown in green). Most prodrug approaches
require a ‘synthetic handle’ on the drug, which are typically heteroatomic groups.
OR
O
R1
O
O
R2
S
R1
O
O
R2
Ethers
S
O
R
O
OR
O
O
R1
O
O
R2
Esters
O
O
OR
Carbonates
O
O
NR
Carbamates
O
NHR
Amides
N
H
O P
O
OH
OH
O O P
O
OH
OH
O P
O
OH
OH
Phosphates
N
R
Imines
N
OR
Oximes
N
H
N
O
R2
R1
N-Mannich bases
–PO(OH)2
–SH
–COOH
–NH
–C O
–OH
Drug Drug PromoietyDrug
Drug
+
Enzymatic
and/or chemical
transformation
Barrier
a
b
Promoiety Promoiety
should be considered with respect to the disease
dose and the duration of therapy.
• Parent and prodrug: the absorption, distribu
metabolism, excretion (ADME) and pharmacoki
properties need to be comprehensively underst
• Degradation by-products: these can affect chem
and physical stability and lead to the formatio
new degradation products.
Some of the most common functional groups th
amenable to prodrug design include carboxylic, hydr
amine, phosphate/phosphonate and carbonyl gro
Prodrugs typically produced via the modification of
groups include esters, carbonates, carbamates, am
phosphates and oximes. However, other uncom
functional groups have also been investigated as p
tially useful structures in prodrug design. For exam
thiols react in a similar manner to alcohols and ca
derivatized to thioethers18
and thioesters19
. Amines
bederivatizedintoimines20,21
andN-Mannichbases22
prodrug structures for the most common functiona
are illustrated in FIG. 1b and discussed below.
Esters as prodrugs of carboxyl, hydroxyl and thiol
tionalities. Esters are the most common prodrugs
anditisestimatedthatapproximately49%ofallmar
prodrugs are activated by enzymatic hydrolysis4
.
prodrugs are most often used to enhance the lipophi
and thus the passive membrane permeability, of w
soluble drugs by masking charged groups such as
boxylic acids and phosphates3,23
. The synthesis of an
prodrug is often straightforward. Once in the bod
ester bond is readily hydrolysed by ubiquitous este
found in the blood, liver and other organs and tiss
including carboxylesterases, acetylcholinester
butyrylcholinesterases, paraoxonases and arylester
However, one significant challenge with ester prodr
the accurate prediction of pharmacokinetic dispos
in humans, owing to significant differences in sp
carboxylesterase activities in preclinical species
Figure 1 | A simplified representative illustration of the prodrug concept.
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive.
Common functional groups on parent drugs that are amenable to prodrug design

4. Chemical bond Enzymes
Esters
Esterase found in the blood, liver and other organs and tissues i.e
1. Carboxylesterases
2. Acetylcholinesterases
3. Butyrylcholinesterases
4. Paraoxonases
5. Arylesterases
Phosphate esters Phosphatase present at the intestinal brush border or in liver
1. Carbonates
2. Carbamates
Esterase
Amides
1. Carboxylesterase
2. Peptidase
3. Protease
Oximes Versatile microsomal Cytochrome P450 (CYP450) enzymes
Enzymes responsible for cleaving of a particular chemical bond

5. SIMVASTATIN
[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]
2,2-dimethylbutanoate
Chemical Structure
Molecular Formula:
Molecular Weight :
C25H38O5
418.56622 g/mol
Therapeutic area : Hypercholesterolaemia

6. Side effects
• Increased urination
• Joint pain
• Loss of consciousness
• Lower back or side pain
• Nasal congestion
• Nausea
• Runny nose
• Sneezing
• Sore throat
• Stomachache
• Sweating
• Swollen joints
• Troubled breathing
• Weight loss
• Vomiting
• Dizziness
• Fainting
• Bladder pain
• Bloody or cloudy urine
• Blurred vision
• Body aches or pain
• Cough
• Dark-colored urine
• Difficult, burning, or painful urination
• Difficulty with breathing
• Dry mouth
• Ear congestion
• Fever
• Dry skin
• Headache
• Increased hunger
• Increased thirst
Synthetic, SemisyntheticSource :
Class : Statins
Route of Administration : Tablet
Prodrug Type: IA

7. Simvastatin Metabolite active openacid
Estereases, Paraoxonases
Non-enzymatic hydrolysis
Statin open acid
Oxidation(P450s)
Binds to
HMG CoA reductase
Inhibit
synthesis of
Mevalonic Acid
Cholesterol
Mechanism of Action

8. Constituent chemicals Brand name
Simvastatin Zocor
Ezetimibe+Simvastatin Vytorin
Niacin+Simvastatin Simcor
Simvastatin+Sitagliptin Juvisync
Trade Names

9. LEVODOPA
Chemical Structure
(2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid
Molecular Formula:
Molecular Weight :
C9H11NO4
197.18794 g/mol
Therapeutic area : Parkinson’s Disease

10. Sources
Mucuna pruriens
Velvet bean
Vicia faba
Broadbean, Horsebean
Phanera
Orchid tree
Cassia
Golden shower tree
Canavalia
Jack bean
Plant Sources

11. Sources
Enzymatic Synthesis
1. Catechol
2. Sodium pyruvate
3. Ammonium acetate
Mushroom tyrosinase
L-Dopa
Fungal Source
1. L-tyrosine
2. Lascorbic acid
Fungal mycelia under optimized condition
L-Dopa
Bacterial Source
Recombinant Escherichia herbicola L-Dopa
Mutant transcripttional
regulator TyrR
Having
Synthesis
Class : Dopaminergic antiparkinsonism agents
Prodrug Type : IA

12. Mechanism of Action
Parkinson's disease
Neurodegeneration of the
extrapyramidal nervous system
Affect the mobility and control of the skeletal muscular system
Depletion of dopamine
in the corpus striatum
Dopamine
Levodopa
blood-brain barrier
Dopamineblood-brain barrier levodopa
Decarboxylase
CNS

13. • Dizziness
• Loss of appetite
• Diarrhea
• Dry mouth
• Mouth and throat pain
• Constipation
• Change in sense of taste
• Forgetfulness or confusion
• Nervousness
• Nightmares
• Difficulty falling asleep or staying asleep
• Headache
• Weakness
Side effects
Formulations available
Constituent chemicals Brand name
Carbidopa + Levodopa Duopa, Rytary, Parcopa, Sinemet
Carbidopa + Levodopa +
Entacapone
Stalevo

14. CAPECITABINE
Chemical Structure
Pentyl N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate
Molecular Weight :
Molecular Formula:
359.350083 g/mol
C15H22FN3O6
Therapeutic area : Cancer Treatment

15. Side effects
• Nausea
• Vomiting
• Loss of appetite
• Constipation
• Tiredness, weakness
• Back/joint/muscle pain
• Headache
• Trouble sleeping
• Skin darkening or dry/itchy skin
• Nausea and vomiting
• Changes in diet and lifestyle
• Temporary hair loss(hair growth return after treatment)
SyntheticSource :
Class : Antimetabolite
Route of Administration : Oral: Tablets
Prodrug Type : IIA

16. INTESTINE
Capecitabine
LIVER
Capecitabine
5’-DFCR
Cytidine
deaminase
5’--DFUR
FU
liver carboxylesterase
TUMOR
5’-DFCR
Cytidine
deaminase
5’--DFUR
Thymidine
phosphorylase
Mechanism of Action
*Thymidine
phosphorylase
10 times more activated in Tumor cells

17. Dosage (mg) Brand Name
500
Capegard, Capget, Capehope, Capiibine(500 mg),Capres,
Capscare(500mg) , Captabin, Capxcel, Distamine(500mg),
Naprocap , Xabine, Xabine , Xeloda
250 Xelocel
150 Capres (150 mg), Distamine (150mg), Capiibine
Trade Names & Dosage

18. Directed Enzyme Prodrug Therapy (DEPT)
Desired Location For Drug Targeting
Enzyme
Artificial Incorporation of Enzym
e
5 Types
Enzyme

19. 1. Antibody-directed enzyme prodrug therapy (ADEPT)
2. Gene-directed enzyme prodrug therapy (GDEPT)
Enzyme

20. 3. Virus-directed enzyme prodrug therapy (VDEPT)
4. Polymer-directed enzyme prodrug therapy (PDEPT)

21. 5. Clostridia-directed enzyme prodrug therapy (CDEPT)
*PCE = Prodrug Cleavage Enzyme

22. Thank You