This document provides an overview of targets for anticancer drug development. It discusses that molecularly targeted agents have proven ineffective or caused toxicity issues. Common targets discussed include nucleic acids, enzymes, hormones, structural proteins, and signaling pathways. Recent research focuses on kinase inhibitors, microtubules, cancer stem cells, MDR pathways, monoclonal antibodies, and multi-targeting agents. The conclusion emphasizes the need for multitargeted approaches and selective use of gene and monoclonal antibody therapies due to resistance mechanisms in cancer cells.

1. GUIDED BY :
DR. S. J. PAWAR
HOD OF DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
PRESENTED BY :
MISS. DHANASHRI VIJAY ZOPE
M.PHARM (PHARMACEUTICAL CHEMISTRY)
ROLL NO : 34
PUNE DISTRICT’S EDUCATION ASSOCIATION’S
SETH GOVIND RAGHUNATH SABLE COLLEGE OF
PHARMACY, SASWAD
TARGETS FOR ANTICANCER DRUG DEVELOPMENT
1

2. Table of
contents
04
03
INTRODUCTION
TARGETS FOR
ANTICANCER DRUG
DEVELOPMENT
05
CURRENT RESEARCH IN
ANTICANCER DRUG
DEVELOPMENT
CONCLUSION
REFERENCES
01
02
2

3. INTRODUCTION
 Drug : A drug is an agent which modifies a drug target in order to bring about a
change in the functionality of that target. Drugs may reduce or accelerate target
activity.
 Drug targets : Drug targets are macromolecules that have a binding site onto which
the drug fits or bind (by intermolecular bonds)
3

4. Lipids Cell membrane
lipids
Proteins
receptors, enzymes,
carrier proteins,
structural proteins
Nucleic
acid
DNA, RNA Carbohydrate
s
cell surface
carbohydrates,
antigens
4

5. TARGETS FOR ANTICANCER DRUG DEVELOPMENT
 Molecularly targeted agents proved ineffective
 Efficacy or toxicity concerns.
 Goal: Complete eradication of disease.
 30% of research focus on finding kinase inhibitors.
 Tubulin/microtubule, cancer stem cells and MDR pathways are hot targets.
 Monoclonal antibodies and multi-targeting anticancer agents.
5

6. Drug targets for anticancer activity
Enzymes
Hormone
s
Structural
proteins
Nucleic
acids
Other
targets
Signaling
pathways
6

7. NUCLEIC ACIDS AS TARGETS FOR ANTICANCER ACTIVITY
 Nucleic acids are naturally occurring chemical compounds that serve as the primary
information-carrying molecules in cells.
 Important role in directing protein synthesis
 They determine the inherited characteristics of every living thing.
 Drugs which act on the nucleic acid targets contains a aromatic ring that slips into the
DNA/RNA of cancer cells and distort its structure.
 One of the most important anticancer drug acting on DNA is called either adriamycin or
doxorubicin.
 Other examples are mitomycin c, ifosfamide, bleomycin (antibiotic) and vitravene.
7

8. Topoisomerase II
Doxorubicin
3HC
CH3
Doxorubicin
8

9. Mitomycin c
9

10. ENZYMES AS TARGET FOR ANTICANCER DRUG DEVELOPMENT
 Enzymes are body’s catalysts agents that speed up a chemical reaction without being consumed
themselves. Without them the cells chemical reaction would either be too slow or not take place at all.
 The active site of an enzyme has to be on or near the surface of the enzymes if the substrate has to
reach it.
 The amino acid present in the active site play an important role in the enzyme function, drugs which
target enzymes bind on this active site and deactivate the enzyme. so that further reaction due to
enzymes can not be take place.
10

11. Enzymes Examples Structure
Dihydrofolate reductase Methotrexate
Pralatrexate
Pemetrexate
Methotrexate
Thymidylate synthase Raltitrexed
Pemetrexed
5-flurouracil
Raltitrexed
Ribonucleiotide reductase Triapine
Hydroxyurea
Triapine
Adenosine deaminase Pentostatin
Allopurinol
Pentostatin
11

12. Enzymes Examples Structure
DNA polymerases Fludarabine
Gemcitabine
Fludarabine
Matrix metalloproteinase Batimastat
Marimastat
Batimastat
Cyclooxygnase II Celecoxib
rofecoxib
Celecoxib
Proteasome Bortezomib
Carfilzomib
Bortezomib
12

13. Enzymes Examples Structure
Histone deacetylase Belinostat
Panabiostat
Resminostat
Belinostat
Tolomerase 3′-azido-3′-deoxythymidine (AZT)
Caspases (activation) Daunorubicin
Doxorubicin
Daunorubicin
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14. HORMONES AS TARGET FOR ANTICANCER DRUGS
 Hormones are proteins or substances made by the body that help to control certain
types of cells work.
 Hormone therapy
 Cancers depending on hormones
 Different from surgery and radiation therapy
14

15. Hormones Examples Structure
Glucocorticoids,
Progestins
Prednisone,
Oestradiol,
Megestrol acetate,
Fluoxymesterone
Prednisone oestradiol
LHRH Leuprolide,
Goserelin
Oestrogens Tamoxifen,
Raloxifene
15

16. Hormones Examples Structure
Androgens Flutamide,
Cyproterone acetate
16

17. STRUCTURAL PROTEINS AS TARGET FOR ANTICANCER ACTIVITY
 Tubulin is a structural protein which is crucial to cell division.
 Building block for microtubules.
Mechanism Example Structure
Inhibition of Tubulin polymerization Vincristine,
Vinblastin,
Phyllanthoside
Inhibition of tubulin depolymerization Colchicine,
Paclitaxel,
Discofermolide
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18. TARGETING SIGNALING PATHWAYS FOR ANTICANCER ACTIVITY
 Describes a series of chemical reactions.
 Abnormal activation of signaling pathways may lead to diseases, such as cancer.
 Drugs are being developed to target specific molecules involved in these pathways. These drugs may help
keep cancer cells from growing.
Signaling protein Example Structure
Farnesyl transferase and Ras protein Lonafarnib
18

19. TARGETING SIGNALING PATHWAYS FOR ANTICANCER ACTIVITY
 Protein kinases are enzymes which phosphorylate specific amino acids in protein substrate.
 Traverse the cell membrane and play a dual role as receptor and enzymes.
 Activated by chemical messengers.
 Chemical messengers can be growth hormones and growth factors.
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20. Protein kinases receptors Examples Structure
Epidermal growth factor receptor
(EGF-R)
Gefitinib,
Erlotinib,
Lapatinib
Abelson tyrosine kinase Imatinib,
Nilotinib,
Dasatinib
TYROSINE SERINE
20

21. Protein kinase receptors Examples Structure
Cyclin-dependent kinases Flavopiridol,
Roscovitine
FGF-R and VEGF-R Sorafenib,
Sunitinib
Multi tyrosine receptor kinase Vatalanib,
Sorafenib,
Sunitinib
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22. 01
04
03
02
05
MONOCLONAL ANTIBODIES
PROTEIN THERAPY
ANTIBODY
DIRECTED ENZYME
PRODRUG THERAPY
GENE DIRECTED
ENZYME PRODRUG
THERAPY
Other Therapies
Activate body’s immune response to
direct killer cells against tumor cells
Certain proteins
stimulates the apoptosis
Antibody-enzyme
complex binds to
tumor and prodrug is
activated
Genes packed inside virus
are delivered to tumor
cells
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23. Drugs and their approved year Type of cancer Target
Mirvetuximab (05/2022) Ovarian cancer Antibody-drug conjugate
Bevacizumab (2022) Ovarian cancer Tyrosine kinase (VEGF)
Dostarlimab (08/2021) Endometrial cancer Monoclonal antibody
Alpelisib (05/2022) PIK3CA related overgrowth PI3K(Phosphatidylinositol-3-
kinase)
Asaminib (10/2021) Chronic myeloid leukemia Tyrosine kinase
Tisotumab (09/2021) Cervical cancer Antibody drug conjugate
Mobocertinib (09/2021) Non small cell lung cancer Kinase (EGFR)
Zanubrutinib (09/2021) Refractory marginal zone
lymphoma
Tyrosine kinase
RECENT DRUGS IN ANTICANCER DRUG DEVELOPMENT
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24. CONCLUSION
 Cancer is a multifactorial disease and so far single target approach for its complete eradication proved
in-effective. Cancer cells develop multiple and complex mechanisms to evade the drug induced
cytotoxicity So, a better understanding of the resistance mechanisms is crucial for the success of
chemotherapy.
 Instead of targeting only one target multitargeted system should be chosen.
 Tyrosine kinase is the most potent and recently used target for the anticancer drug development.
 Whereas, other therapies like gene therapy and monoclonal antibodies have selective role at the cancer
cell target only so their use for cancer treatment is preferred.
24

25. REFERENCES
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4. Robert E. Smith, Medicinal chemistry – fusion of traditional and western medicine “Drugs that act on DNA and
RNA “ volume 1(7) 329-335
5. Maria Valeria Raimondi, Ornella Randazzo, Mery La Franca, Giampaolo Barone, Elisa Vignoni, Daniela
Rossi, and Simona Collina DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents
Molecules. 2019 Mar; 24(6): 1140
6. Edward Chu, Marc A. Callender, Michael P. Farrell, John C. Schmitz Thymidylate synthase inhibitors as
anticancer agents: from bench to bedside Cancer Chemother Pharmacol (2003) 52 (Suppl 1): S80–S89 25

26. 7. Tobias R. Chapman and Timothy J. Kinsella Ribonucleotide Reductase Inhibitors: A New Look at an Old Target for
Radio sensitization Front oncol. 2011; 1: 56
8. Anthony J. Berdis inhibiting DNA polymerases as therapeutic intervenation for anticancer agents, molecular
diagnostic and therapeutics 21 November 2017 pg. no 1-10
9. Manuel Hidalgo, S. Gail Eckhardt Development of Matrix Metalloproteinase Inhibitors in Cancer
Therapy Journal of the National Cancer Institute, Volume 93, Issue 3, 7 February 2001, Pages 178–193
10. Alane T Koki , Jaime L Masferrer Celecoxib: a specific COX-2 inhibitor with anticancer properties Cancer
Control. Mar-Apr 2002;9(2 Suppl):28-35
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Drugs Int J Mol Sci 2017 Jul 1;18(7):1414
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27. 12. Maria Valeria Raimondi, Ornella Randazzo, Mery La Franca, Giampaolo Barone, Elisa Vignoni, Daniela Rossi,
Simona Collina DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents
Molecules 2019, 24(6), 1140
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29. ACKNOWLEDGEMENT
 Dr. R. S. Chavan
(Principal of PDEA’s Seth Govind Raghunath Sable College Of Pharmacy )
 Dr. S. J. Pawar
(H.O.D. of pharmaceutical chemistry)
 Prof. J. R. Jagtap
(Assistant professor of pharmaceutical chemistry)
 Prof. A. P. Kale
(Assistant professor of pharmaceutical chemistry)
 Prof. G. B. Nigade
(Assistant professor of pharmaceutical chemistry) 29

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