ACS San Diego, March 2012, InChI Symposium

Accessing NCI/CADD Web Resources by InChI
Markus Sitzmann
Computer-Aided Drug Design Group, Chemical Biology Laboratory,
Frederick National Laboratory for Cancer Research, NIH, DHHS

Chemical Identifier Resolver (CIR)

CIR works as a resolver for different
chemical structure identifiers or
representations.
It allows one to convert a given
structure identifier into another
representation or structure
identifier.

http://cactus.nci.nih.gov/chemical/structure

Chemical Structure Representations

SYBYL Line Notation
SMILES CAS Registry Number
chemical names
GIF image
ChemNavigator SID SD File

chemical structure
CML

FDA UNII

NCI/CADD Identifiers
NSC number
MRV

InChI/InChIKey
PubChem SID/CID
ChemSpider ID
ChEBI ID
Chemical Formula PDB Ligand ID

Chemical Structure Representations

SYBYL Line Notation
SMILES CAS Registry Number
chemical names
GIF image
ChemNavigator SID SD File
CML
InChI FDA UNII

NCI/CADD Identifiers
NSC number
MRV

InChI/InChIKey
PubChem SID/CID
ChemSpider ID
ChEBI ID
Chemical Formula PDB Ligand ID

Chemical Structure Databases

InChI

many more …

C7H6O2
APtclcactv03051222202D 0 0.00000 0.00000

WPYMKLBDIGXBTP-FZOZFQFYNA-N 15 15 0 0 0 0 0 0 0 0999 V2000
2.8660 -2.0600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.7321 -1.5600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.7321 -0.5600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.8660 -0.0600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.0000 -0.5600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.0000 -1.5600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
Works as a resolver for different
2.8660 0.9400 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.7321 1.4400 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
chemical structure identifiers.
2.0000 1.4400 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
2.8660 -2.6800 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
Allows one to convert a given
4.2690 -1.8700 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
4.2690 -0.2500 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
1.4631 -0.2500 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
1.4631 -1.8700 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
3.7321 2.0600 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0 0 0 0
2 3 1 0 0 0 0
identifier.
3 4 2 0 0 0 0
4 5 1 0 0 0 0
5 6 2 0 0 0 0
1 6 1 0 0 0 0
4 7 1 0 0 0 0
7 8 1 0 0 0 0
7 9 2 0 0 0 0
1 10 1 0 0 0 0
2 11 1 0 0 0 0
3 12 1 0 0 0 0

5 13 1 0 0 0 0
6 14 1 0 0 0 0
8 15 1 0 0 0 0
ChemWriter Editor M END
SD file $$$$

benzoic acid
65-85-0
WLN: QVR
WPYMKLBDIGXBTP-FZOZFQFYNA-N Unisept BZA
AIDS018010
Salvo liquid
Benzoic acid-ring-UL-14C
ST5213864
Benzoesaeure
CHEBI:30746
NSC 149
benzenecarboxylic acid
phenylformic acid
Benzoic acid (JP15/USP)
Benzoic acid (TN)
18102_RIEDEL
Aromatic hydroxy acid
Benzoic acid (7CI,8CI,9CI)
Benzoic acid [USAN:JAN]
W213128_ALDRICH
47849_SUPELCO
identifier.
Acide benzoique [French]
Acido benzoico [Italian]
Benzoate (VAN)
Benzoesaeure [German]
Benzoic acid (natural)
Acide benzoique
Benzeneformic acid
Benzenemethanoic acid
Benzoesaeure GK
Benzoesaeure GV

Benzoic acid, tech.
Carboxybenzene
Kyselina benzoova
ChemWriter Editor Phenylcarboxylic acid
names


WPYMKLBDIGXBTP-FZOZFQFYNA-N

InChIKey=WPYMKLBDIGXBTP-UHFFFAOYSA-N
InChI=1S/C7H6O2/c8-7(9)6-4-2-1-3-5-6/h1-5H,(H,8,9)
C1=CC=C(C=C1)C(O)=O

identifier.

InChIKey
InChI
ChemWriter Editor
SMILES


programmatic URL API:

http://cactus.nci.nih.gov/chemical/structure/”identifier”/”representation”

if a request is not successful: HTTP404 status message


examples:
programmatic URL API:
http://cactus.nci.nih.gov/chemical/structure/PGZUMBJQJWIWGJ-ONAKXNSWSA-N/cas

204255-11-8 MIME type: text/plain

http://cactus.nci.nih.gov/chemical/structure/”identifier”/”representation”
http://cactus.nci.nih.gov/chemical/structure/PGZUMBJQJWIWGJ-ONAKXNSWSA-N/image

if a request is not successful: HTTP404 status message
MIME type: image/gif


• access by programming libraries/languages (e.g. Python):
from urllib2 import *
url = “http://cactus.nci.nih.gov/chemical/structure/tamiflu/cas”
resolver = urlopen(url)
try:
response = resolver.read()
except HTTPError:
raise “your own error handling”
print response
204255-11-8

• access from Unix shell level (e.g., via wget):
shell > wget -qO -
http://cactus.nci.nih.gov/chemical/structure/tamiflu/cas
204255-11-8

Chemical Identifier Resolver: InChI/InChIKey

Database RegIDs
structure images (PubChem, ZINC, eMolecules, ChemSpider ID)
(GIF, PNG)

(trivial) names SMILES
InChI/InChIKey

IUPAC names (OPSIN)
chemical properties
(MW, formula, …)
CAS Registry numbers
structure files (sdf, pdb, cdx, …)


/smiles
chemical names /names, /iupac_name
IUPAC names (OPSIN) /cas
CAS numbers /inchi, /stdinchi
SMILES strings /inchikey, /stdinchikey
IUPAC InChI/InChIKeys /ficts, /ficus, /uuuuu
NCI/CADD Identifiers /image
CACTVS HASHISY CIR /file, /sdf
NSC number http://cactus.nci.nih.gov/chemcial/structure /mw, /monoisotopic_mass
PubChem SID /formula
ZINC Code /twirl
ChemSpider ID /urls
ChemNavigator SID /chemspider_id
eMolecule VID /pubchem_sid
/chemnavigator_sid

“identifier” “representation”


identifier representation
http request

calculation of the http response
identifier is a
full structure requested structure
representation representation
detection of (e.g. SMILES, InChI)
the identifier MIME type
type e.g. InChI, GIF image

identifier is a
e.g. CAS number,
hashed structure structure chemical name
representation
(e.g. InChIKey),
chemical name etc.

database lookup CSDB

Chemical Structure Database (CSDB)

• ChemNavigator iResearch Library
compilation of commercially available screening
compounds from ~300 international chemistry
suppliers PubChem
ChemNav. ~38%
• PubChem database iResearch Lib.
including Open NCI database, EPA DSSTox ~56%
databases, NIAID HIV database, NIST Webbook,
NLM ChemIDplus, ChemSpider, …
~6%
• Commercial Sources / others others
Asinex, Comgenex, eMolecules, …

current status: 140 chemical structure databases
(as of March 2010) 120 million structure records
84.6 million unique structures by FICuS
110 million Standard InChIKeys for lookup

Chemical Structure Database (Update 2012)

• PubChem Substance & Compound as separate databases
(both updated to 2012)
• ChemNavigator iResearch Library: updated to 2012
• new databases, e.g.
• Therapeutic Target Database (TTD)
• Human Metabolome Database (HMDB)
• DrugBank
• “pull” download of databases also available in PubChem, e.g.
• DSSTox, ZINC 2012/01, ChEBI 2012/01, ChEMBL13,
ChemIDplus 2012/01
• to a limited extend “historic versions” of databases are archived,
e.g. comparison of PubChem Substance 2007 vs 2012 will be
possible

Chemical Structure Normalization

• calculation of a set of parent structures with different
sensitivity to chemical features:

structure hashcode
original normalization calculation
parent NCI/CADD
structure
structure Identifier
record
E_HASHISY
Molfile SDF FICTS
SDF SMILES
SMILES database FICuS
ChemDraw cdx
PDB uuuuu

both the original structure record & the normalized parent structures
are archived in the database

NCI/CADD Identifiers (FICTS, FICuS, uuuuu)

based on CACTVS hashcodes (HASHISY) O

16-digit hexadecimal number (64-bit unsigned) HN OH
N NH 2

9850FD9F9E2B4E25
structure normalization:
O O O O O
Na+
HN OH N OH HN O- HN OH HN OH
N NH NH NH2 N NH2 N NH2 N NH2

histidine: tautomer salt R S

9850FD9F9E2B4E25-FICTS 6C16DE2351F9FF50-FICTS E5F83F10C5DB080A-FICTS E92E4BA2869F3611-FICTS 8A7AD1EB498CC76A-FICTS

9850FD9F9E2B4E25-FICuS E5F83F10C5DB080A-FICuS E92E4BA2869F3611-FICuS 8A7AD1EB498CC76A-FICuS

9850FD9F9E2B4E25-uuuuu


Unique structure count: (HASHISY)
based on CACTVS hashcodes O

16-digit hexadecimal number (64-bit unsigned) HN OH
FICTS ~118 million N NH 2

FICuS ~115 million 9850FD9F9E2B4E25
structure normalization:
uuuuu ~100 million
O O O O O
Na+
HN OH N OH HN O- HN OH HN OH
N NH NH NH2 N NH2 N NH2 N NH2
histidine: tautomer salt R S

231 small-molecule database
9850FD9F9E2B4E25-FICTS 6C16DE2351F9FF50-FICTS E5F83F10C5DB080A-FICTS E92E4BA2869F3611-FICTS 8A7AD1EB498CC76A-FICTS

367 database releases (full, incremental, “historic versions”)
9850FD9F9E2B4E25-FICuS E5F83F10C5DB080A-FICuS E92E4BA2869F3611-FICuS 8A7AD1EB498CC76A-FICuS

324 million original database records 9850FD9F9E2B4E25-uuuuu

InChI/InChIKey

InChI/InChIKey (Version 1.04) calculated with four InChI flag sets:

CACTVS
Standard : Add H Standard InChIKey

Set 1 : Add H DONOTADDH W0 FIXEDH RECMET NEWPS SPXYZ SAsXYZ Fb Fnud KET 15T



Standard Set, Set 1 & Set 2: addition of hydrogen atoms by CACTVS
Set 3: addition of hydrogen atoms by the InChI library

InChI/InChIKey

• calculation of InChI/InChIKey Standard set, Set 1, Set 2 & Set 3
for all original structure records and normalized parent structure:

structure hashcode
original normalization calculation
parent NCI/CADD
structure
structure Identifier
record
E_HASHISY
FICTS

FICuS

uuuuu
InChI/InChIKey

Standard Set 1 Set 2 Set 3

Using CIR with InChI/InChIKey
(Partial) InChIKey Lookup

• resolve Standard InChIKey into full structure representation:
Ethanol
http://cactus.nci.nih.gov/chemical/structure/LFQSCWFLJHTTHZ-UHFFFAOYSA-N/smiles

CCO

http://cactus.nci.nih.gov/chemical/structure/LFQSCWFLJHTTHZ-UHFFFAOYSA/smiles`

CCO
CC[OH2+]

http://cactus.nci.nih.gov/chemical/structure/LFQSCWFLJHTTHZ/smiles

C(C(O)([2H])[2H])[2H]
CC(O)([2H])[2H]
C(CO)([2H])([2H])[2H]
CC[17OH]
C(CO)[2H]
[14CH3]CO
CCO

Chemical File Representation

• available file format representations:
Aspirin
http://cactus.nci.nih.gov/chemical/structure/BSYNRYMUTXBXSQ-UHFFFAOYSA-N/file?format=sdf

alc Alchemy format maestro Schroedinger MacroModel
cdxml CambridgeSoft ChemDraw XML format structure file format
cerius MSI Cerius II format mol Symyx molecule file
charmm Chemistry at HARvard sybyl2/mol2 Tripos Sybyl MOL2 format
Macromolecular Mechanics file format mrv ChemAxon MRV format
cif Crystallographic Information File pdb Protein Data Bank
cml Chemical Markup Language sdf Symyx Structure Data Format
gjf Gaussian input data file sdf3000 Symyx Structure Data Format 3000
gromacs GROMACS file format sln SYBYL Line Notation
hyperchem HyperChem file format smiles SMILES
jme Java Molecule Editor format xyz xyz file format

Chemical Structure Images (GIF, PNG)

Buckyball

http://cactus.nci.nih.gov/chemical/structure/
XMWRBQBLMFGWIX-UHFFFAOYSA-N/image
?height=300&width=300&bgcolor=black&bondcolor=white

Aspirin
BSYNRYMUTXBXSQ-UHFFFAOYSA-N/image
?height=200&width=200&symbolfontsize=7&footer="Aspirin"

3D Chemical Structure Visualization (TwirlyMol)

simple javascript that allows you to render a rotatable/zoomable
3D representation of a molecule in your web browser

implemented by Noel O'Boyle (University College Cork, Ireland)

no plugin is needed, only a modern browser:
Chrome Safari FF3.6+ IE9 IE8 IE7 IE6


simple viewer: Restasis
http://cactus.nci.nih.gov/chemical/structure/DDPJWUQJQMKQIF-XPNZOOHZSA-N/twirl

embedded into a web page:

<div id=“canvas” height=“400” width=“400”></div>
<script src=“http://cactus.nci.nih.gov/chemical/structure/
DDPJWUQJQMKQIF-XPNZOOHZSA-N/twirl_cached/canvas” />


http://baoilleach.blogspot.com/

http://www.coronene.com/blog/

http://chemical-quantum-images.blogspot.com

Chemical Database URLs

• request database URLs:
Restasis
http://cactus.nci.nih.gov/chemical/structure/DDPJWUQJQMKQIF-XPNZOOHZSA-N/urls/xml

<?xml version="1.0" encoding="UTF-8" ?>
<request string="DDPJWUQJQMKQIF-XPNZOOHZSA-N" representation="urls">
<data id="1" resolver=“stdinchikey" string_class=“Standard InChIKey">
<item id="1" classification="exact" database="ChemSpider" publisher="ChemSpider">
http://chemspider.com/structure.4939506
</item>
<item id="2" classification="exact" database="ChemSpider“ publisher="PubChem">
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=43028058
</item>
<item id="3" classification="exact" database="NLM ChemIDplus" publisher="NLM">
http://chem.sis.nlm.nih.gov/chemidplus/direct.jsp?result=advanced&regno=059865133
[…]
</data>
</request>

Chemical Name Lookup

• request (alternative) names:
Aspirin
http://cactus.nci.nih.gov/chemical/structure/BSYNRYMUTXBXSQ-UHFFFAOYSA-N/names/xml

<?xml version="1.0" encoding="UTF-8" ?>
<request string=“BSYNRYMUTXBXSQ-UHFFFAOYSA-N" representation="names">
<data id="1" resolver=“stdinchikey" string_class=“Standard InChIKey">
<item id="1" classification=“pubchem_iupac_name">2-acetyloxybenzoic acid</item>
<item id="2" classification="pubchem_iupac_openeye_name">2-Acetoxybenzoic acid</item>
<item id="3" classification="pubchem_generic_registry_name">50-78-2</item>
<item id="8" classification="pubchem_substance_synonym">NCGC00090977-04</item>
<item id="9" classification="pubchem_substance_synonym">KBioSS_002272</item>
<item id="10" classification="pubchem_substance_synonym">SBB015069</item>
<item id="11" classification="pubchem_substance_synonym">Aspirin</item>
<item id="12" classification="pubchem_substance_synonym">D00109</item>
[…]

Chemical Properties

• request molecular weight:
Aspirin
http://cactus.nci.nih.gov/chemical/structure/BSYNRYMUTXBXSQ-UHFFFAOYSA-N/weight

180.1598 MIME type: text/plain

/mw molecular weight /aromatic compound is aromatic
/formula formula /macrocyclic compound is macrocyclic
/monoisotopic_mass monoisotopic mass /heteroatom_count heteroatom count
/h_bond_donor_count H bond donor count /hydrogen_atom_count H atom count
/h_bond_acceptor_count H bond acceptor count /heavy_atom_count heavy atom count
/h_bond_center_count H bond center count /deprotonable_group_count number of
/rotor_count number of rotatable bonds deprotonable groups
/effective_rotor_count number of effectively /protonable_group_count number of
rotatable bonds protonable groups
/rule_of_5_violation_count number of Rule-of-5 /ring_count number of rings
violations /ringsys_count number of ringsystems
/xlogp2 octanol−water partition
coefficient XLOGP2

Chemical Name Pattern Search

• Google-like searches on CIR’s name index (approx. 70 million names)

example: all chemical names that contain the words “morphine” and “methyl”
(name pattern: ‘+morphine +methyl‘):

http://cactus.nci.nih.gov/chemical/structure/+morphine +methyl/stdinchikey/xml?resolver=name_pattern

based on the open source
full text search server Sphinx
(http://sphinxsearch.com)

Search name pattern ‘+morphine +methyl’: 7 matching names
<request string="+morphine +methyl" representation="stdinchikey">
<data id="1" resolver="name_pattern" notation="Morphine 3-methyl ether">
<item id="1">InChIKey=OROGSEYTTFOCAN-DNJOTXNNSA-N</item>
</data>
<data id="2" resolver="name_pattern" notation="6-Methyl-delta(sup 6)-deoxy-morphine">
<item id="1">InChIKey=CUFWYVOFDYVCPM-GGNLRSJOSA-N</item>
</data>
<data id="3" resolver="name_pattern" notation="Morphine, dihydro-6-methyl-">
<item id="1">InChIKey=NBKVWIJQJMEQLE-NGTWOADLSA-N</item>
</data>
<data id="4" resolver="name_pattern“ notation="6-METHYL-MORPHINE ETHER">
<item id="1">InChIKey=FNAHUZTWOVOCTL-UHFFFAOYSA-N</item>
</data>
<data id="5" resolver="name_pattern" notation="Morphine alcoholic methyl ether">
<item id="1">InChIKey=FNAHUZTWOVOCTL-XSSYPUMDSA-N</item>
</data>
<data id="6" resolver="name_pattern" notation="N-Methyl morphine chloride">
<item id="1">InChIKey=MJNCZWBHCFTYFU-SCLAZZCHSA-N</item>
</data>
<data id="7" resolver="name_pattern" notation="Morphine, 7-hydroxy-6,6-dimethoxy-3-O-methyl-">
<item id="1">InChIKey=URFKRBIESURBKC-UHFFFAOYSA-N</item>
</data>
</request>

Chemical Name Pattern Search

example: chemical names that contain the words “morphine” and “methyl”
but not “hydroxyl” (name pattern: ‘+morphine +methyl -hydroxyl‘):
http://cactus.nci.nih.gov/chemical/structure/+morphine +methyl -hydroxyl/stdinchikey/xml?resolver=name_pattern

6 matching names

example: chemical names that contain the substring “morphine”
somewhere in the name (name pattern: ‘*morphine*‘)
http://cactus.nci.nih.gov/chemical/structure/*morphine*/stdinchikey/xml?resolver=name_pattern

45 matching names

example: chemical names that contain a single character “m” and the word
“benzene” in a maximum distance of 3 words (finds meta-substituted aromatic
compounds, name pattern: ‘“m benzene”~3‘):
http://cactus.nci.nih.gov/chemical/structure/(m benzene)~3/stdinchikey/xml?resolver=name_pattern

22 matching names

Structure Normalization
(Tautomerism)

Tautomerism

21 SMIRKS transform rules:

rule 1: 1.3 (thio)keto/(thio)enol rule 12: furanones
rule 2: 1.5 (thio)keto/(thio)enol rule 13: keten/ynol exchange
rule 3: simple (aliphatic) imine rule 14: ionic nitro/aci-nitro
rule 4: special imine rule 15: pentavalent nitro/aci-nitro
rule 5: 1.3 aromatic heteroatom H shift rule 16: oxim/nitroso
rule 6: 1.3 heteroatom H shift rule 17: oxim/nitroso via phenol
rule 7: 1.5 (aromatic) heteroatom H shift (1) rule 18: cyanic/iso-cyanic acids
rule 8: 1.5 aromatic heteroatom H shift (2) rule 19: formamidinesulfinic acids
rule 9: 1.7 (aromatic) heteroatom H shift rule 20: isocyanides
rule 10: 1.9 (aromatic) heteroatom H shift rule 21: phosphonic acids
rule 11: 1.11 (aromatic) heteroatom H shift

Tautomerism
rule 1: 1.3 (thio)keto/(thio)enol

1 1 H4
O O
2
2 3 H4 3

1.3 keto/enol

[O,S,Se,Te;X1:1]=[C;z{1-2}:2][CX4R{0-2}:3][#1:4]>>
[#1:4][O,S,Se,Te;X2:1][#6;z{1-2}:2]=[C,cz{0-1}R{0-1}:3]

rule 6: 1.3 heteroatom H shift

4 4
H H 3
1 3
S N 1 S N
2 H H
2
N N
H 1.3 heteroatom H shift H

[N,n,S,s,O,o,Se,Te:1]=[NX2,nX2,C,c,P,p:2][N,n,S,O,Se,Te:3][#1:4]>>
[#1:4][N,n,S,O,Se,Te:1][NX2,nX2,C,c,P,p:2]=[N,n,S,s,O,o,Se,Te:3]

Warfarin - Tautomers

HO O HO O HO O

O O HO O HO O

O O O O O O

O O HO O HO O

O O O O O O

O OH HO OH HO OH

prototropic tautomerism

Warfarin - Tautomers

HO O HO O HO O

O O HO O HO O

O O O O O O

O O HO O HO O

O O O O O O

O OH HO OH HO OH

http://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/representation

Warfarin – FICuS Identifier
FICuS

HO O HO O HO O

O O HO O HO O

D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS

O O O O O O

O O HO O HO O


O O O O O O

O OH HO OH HO OH


http://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/ficus
prototropic tautomerism tautomerism
prototropic

Warfarin – FICuS Identifier
FICuS

HO O HO O HO O O O

O O HO O HO O O
HO
D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS 09BB2FAADA1508A7-FICuS

O O O O O O O O
HO

O O HO O HO O O

D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS 09BB2FAADA1508A7-FICuS

O O O O O O O O
HO

O OH HO OH HO OH OH

D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS 2F505A3FCA434B3C-FICuS

http://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/ficus
ring-chain
ring-chain
prototropic tautomerism tautomerism
prototropic
tautomerism
tautomerism

Warfarin – Standard InChIKey

HO O HO O HO O O O

O O HO O HO O O
HO
QTXVAVXCBMYBJW-UHFFFAOYSA-N VWSXIGYSLWNCBN-VAWYXSNFSA-N GRAAPKVUSREWIL-UHFFFAOYSA-N LSCYDZJASSKSMJ-UHFFFAOYSA-N

O O O O O O O O
HO

O O HO O HO O O

FQEPJUOLUDFINX-UHFFFAOYSA-N UCKRWKACBKRIKB-VAWYXSNFSA-N NNLYDNMZCAHUOV-UHFFFAOYSA-N XGIOTBZTMHLTRL-UHFFFAOYSA-N

O O O O O O O O
HO

O OH HO OH HO OH OH

PJVWKTKQMONHTI-UHFFFAOYSA-N FVSFCRPKSVCTBA-VAWYXSNFSA-N BBOSKMPTDUUMKL-UHFFFAOYSA-N QUJJIKXCACZKKD-UHFFFAOYSA-N

http://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/stdinchikey
ring-chain
tautomerism

Warfarin – InChIKey

HO O HO O HO O O O

O O HO O HO O O
HO
SAYISSDYYDIVTP-UHFFFAOYNA-N SAYISSDYYDIVTP-UHFFFAOYNA-N PMOPDASZKFXBOL-UHFFFAOYNA-N LSCYDZJASSKSMJ-UHFFFAOYNA-N

O O O O O O O O
HO

O O HO O HO O O

SAYISSDYYDIVTP-UHFFFAOYNA-N SAYISSDYYDIVTP-UHFFFAOYNA-N PMOPDASZKFXBOL-UHFFFAOYNA-N FQOKLKCGRHFANU-UHFFFAOYNA-N

O O O O O O O O
HO

O OH HO OH HO OH OH

SAYISSDYYDIVTP-UHFFFAOYNA-N SAYISSDYYDIVTP-UHFFFAOYNA-N PMOPDASZKFXBOL-UHFFFAOYNA-N FQOKLKCGRHFANU-UHFFFAOYNA-N

InChIKey (W0 RECMET NEWPS SPXYZ SAsXYZ Fb Fnud KET 15T)
ring-chain
tautomerism

Warfarin

• “normalize” Standard InChIKey by NCI/CADD’s business rules:
http://cactus.nci.nih.gov/chemical/structure/normalize:QTXVAVXCBMYBJW-UHFFFAOYSA-N/stdinchikey

InChIKey=FQEPJUOLUDFINX-UHFFFAOYSA-N MIME type: text/plain

HO O O O

O O O O

QTXVAVXCBMYBJW-UHFFFAOYSA-N FQEPJUOLUDFINX-UHFFFAOYSA-N

Chemical Operators

• available operators:

add_hyrogens, remove_hydrogens, normalize, ficts, ficus, uuuuu,
scaffold_sequence, nostereo, stereoisomers, tautomers

example:
scaffold_sequence:FQEPJUOLUDFINX-UHFFFAOYSA-N/stdinchikey

O O O O O O

O O O

XVYBSGQBRUYLNK-UHFFFAOYSA-N BQLSCAPEANVCOG-UHFFFAOYSA-N MERGMNQXULKBCH-UHFFFAOYSA-N

Schuffenhauer et al., J. Chem. Inf. Model. 2007, 47, 47-58

Soon: Chemical File Resolver (CFR)

Chemical File Resolver (CFR)

chemical HTTP Post HTTP Get chemical
CFR
file file

• allows conversion of many chemical file formats into another
format or other representations
• will have a programmatic URL API & a HTML Web interface
• url’izes all elements of the original file, i.e. provides access to each
specific record, field, and any metadata (size, record count, etc.) of
the posted file by URLs
• release: Q2/2012 (hopefully)


CFR
file file

• HTTP: post a file (e.g. with curl), CFR replies with a MD5 hash key:

curl -F upload=@/your/local/file.sdf http://cactus.nci.nih.gov/chemical/file
>d85b396ed6ced6348a5b402eb8fcfe8b

• accepted formats:
• chemical file formats: alc, cdxml, cerius, charmm, cif, cml, jme,
maestro, mol, mol2, mrv, pdb, sdf, sdf3000, sln, smiles, xyz, …
• text files with a list of identifiers …

Post a plain text file, e.g.:

ethanol HTTP Post HTTP Get
chemical
aspirin chemical
CFR
file
InChI=1S/C4H10O/c1-3-5-4-2/h3-4H2,1-2H3 file
CCOCC
InChIKey=RCINICONZNJXQF-MZXODVADSA-N
InChIKey=QTXVAVXCBMYBJW-UHFFFAOYSA-N
• 204255-11-8a file, CFR replies with a MD5 hash sum:
after posting
tautomers:guanine
curl -F upload=@/your/local/file.sdf http://cactus.nci.nih.gov/TEST/chemical/file
ChemSpider_ID=1234
>d85b396ed6ced6348a5b402eb8fcfe8b
Pubchem_SID=456

• accepted formats:
• chemical file formats: alc, cdxml, cerius, charmm, cif, cml, jme,
maestro, mol, mol2, mrv, pdb, sdf, sdf3000, sln, smiles, xyz, …
• text files with a list of identifier:


CFR
file file

• request new file format using the obtained MD5 hash key:

d85b396ed6ced6348a5b402eb8fcfe8b

curl http://cactus.nci.nih.gov/TEST/chemical/file/{key}?format={sdf, smi, pdb, cml, …}


CFR
file file

• request record 2 and 5 as SMILES string:

d85b396ed6ced6348a5b402eb8fcfe8b

curl http://cactus.nci.nih.gov/TEST/chemical/file/{key}?records=2,5&format=smiles


CFR
file file

• get field names:

curl http://cactus.nci.nih.gov/TEST/chemical/file/{key}/fields

• get a specific field value from record n:

curl http://cactus.nci.nih.gov/TEST/chemical/file/{key}/n/{field_name}

Chemical Structure Web API

external
Chemical Chemical
NCI/CADD web services
Identifier File
web service
Resolver Resolver

http

Chemical Structure Web API

other
CACTVS software
packages

NCI/CADD Chemical Structure OPSIN
Database (CSDB)

IUPAC InChI/InChIKey Resolver

• (hopefully) there will be many resolvers from different
providers with different background:
• publishers
• commercial databases
• free sources and databases: ChemSpider, PubChem, ChEBI, …
• InChI/InChIKey is the perfect tool to interlink the resolvers
• ChemSpider, PubChem and NCI/CADD are working on a test
protocol for a federated InChI/InChIKey resolver

IUPAC InChI/InChIKey Resolver

Resolver 1

IUPAC Root Resolver

Resolver 2

Resolver 3.1
Resolver 3

Resolver 3.2
Clients Resolver 3
CIR

Resolver 3.3

http://cactus.nci.nih.gov/blog

Acknowledgments

The InChI Team

NCI/CADD Team University of Cambridge, UK
Igor Filippov Daniel Lowe
Marc Nicklaus

Xemistry GmbH, Germany University College Cork, Ireland
Wolf-Dietrich Ihlenfeldt Noel O’ Boyle

All Database providers ChemNavigator
Scott Hutton
Tad Hurst

Acknowledgments - Software

CACTVS

Python Web Framework
ChemWriter

Python SQL Library
Peter Ertl (Novartis)

Javascript library

Fulltext Search Engine

ACS San Diego, March 2012, InChI Symposium

ACS San Diego, March 2012, InChI Symposium

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Editor's Notes