opnurasib   Click here for help

GtoPdb Ligand ID: 11715

Synonyms: compound 5 [PMID: 35404998] | example 1a [WO2021120890A1] | JDQ 443 | JDQ-443 | JDQ443 | Nvp-jdq443
Compound class: Synthetic organic
Comment: Opnurasib (JDQ443) is a clinical stage, covalent KRASG12C inhibitor that is being developed by Novartis for anti-tumour potential. We obtained this structure from a list compiled by DrugHunter of first time disclosures made at the 2021 XXVI EFMC International Symposium on Medicinal Chemistry (EFMC-ISMC). This chemical structure was submitted to PubChem by SureChEMBL in August 2021, and is likely to have originated from a patent extraction. The compound's discovery was published in June 2022 [3]. JDQ443 binds to GDP-bound KRASG12C and traps it in an inactive conformation [2].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 84.63
Molecular weight 525.2
XLogP 5.92
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)N1CC2(C1)CC(C2)n1nc(c(c1C)c1c(Cl)c(C)cc2c1cn[nH]2)c1ccc2c(c1)cnn2C
Isomeric SMILES Cn1ncc2c1ccc(c2)c1nn(C2CC3(C2)CN(C3)C(=O)C=C)c(C)c1c1c(Cl)c(C)cc2c1cn[nH]2
InChI InChI=1S/C29H28ClN7O/c1-5-24(38)36-14-29(15-36)10-20(11-29)37-17(3)25(26-21-13-31-33-22(21)8-16(2)27(26)30)28(34-37)18-6-7-23-19(9-18)12-32-35(23)4/h5-9,12-13,20H,1,10-11,14-15H2,2-4H3,(H,31,33)
InChI Key AZUYLZMQTIKGSC-UHFFFAOYSA-N
References
1. Liu B, Cotesta S, Gerspacher M, Leblanc C, Lorthois ELJ, Machuaer R, Mah R, Mura C, Rigollier P, Schneider N et al.. (2021)
Pyrazolyl derivatives useful as anti-cancer agents.
Patent number: WO2021120890A1. Assignee: Novartis. Priority date: 20/12/2019. Publication date: 24/06/2021.
2. Lorthiois E, Gerspacher M, Beyer KS, Vaupel A, Leblanc C, Stringer R, Weiss A, Wilcken R, Guthy DA, Lingel A et al.. (2022)
JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors.
J Med Chem, 65 (24): 16173-16203. [PMID:36399068]
3. Weiss A, Lorthiois E, Barys L, Beyer KS, Bomio-Confaglia C, Burks H, Chen X, Cui X, de Kanter R, Dharmarajan L et al.. (2022)
Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C.
Cancer Discov, 12 (6): 1500-1517. [PMID:35404998]