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sotorasib   Click here for help

GtoPdb Ligand ID: 10678

Synonyms: AMG 510 | AMG-510 | AMG510 | compound (R)-38 [PMID: 31820981] | Lumakras® | Lumykras®
Approved drug
sotorasib is an approved drug (FDA (2021), EMA (2022))
Compound class: Synthetic organic
Comment: Sotorasib (AMG510) is a covalent KRASG12C inhibitor [2] that was developed by Amgen for anti-tumour potential in KRASG12C-driven cancers. It was the first KRAS-targeting drug to be approved for clinical use. Sotorasib retains activity towards NRASG12C and HRASG12C [3].
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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

sotorasib is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 6
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 103.93
Molecular weight 560.23
XLogP 5.71
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES C=CC(=O)N1CCN([C@H](C1)C)c1nc(=O)n(c2c1cc(F)c(n2)c1c(O)cccc1F)c1c(C)ccnc1C(C)C
Isomeric SMILES C=CC(=O)N1CCN([C@H](C1)C)c1nc(=O)n(c2c1cc(F)c(n2)c1c(O)cccc1F)c1c(C)ccnc1C(C)C
InChI InChI=1S/C30H30F2N6O3/c1-6-23(40)36-12-13-37(18(5)15-36)28-19-14-21(32)26(24-20(31)8-7-9-22(24)39)34-29(19)38(30(41)35-28)27-17(4)10-11-33-25(27)16(2)3/h6-11,14,16,18,39H,1,12-13,15H2,2-5H3/t18-/m0/s1
InChI Key NXQKSXLFSAEQCZ-SFHVURJKSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Sotorasib (AMG510) progressed to Phase 3 clinical evaluation in KRASG12C positive NSCLC. The FDA had granted AMG510 breakthrough-therapy designation for locally advanced or metastatic, pretreated KRASG12C positive NSCLC in 2019. Encouraging Phase 1/2 results were published in late 2020 [1]. Full FDA approval was granted in May 2021, for the indication of KRASG12C-mutated locally advanced or metastatic NSCLC that has been treated with at least one prior systemic therapy.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04303780 Study to Compare AMG 510 "Proposed INN Sotorasib" With Docetaxel in Non Small Cell Lung Cancer (NSCLC) (CodeBreak 200). Phase 3 Interventional Amgen
NCT03600883 A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreak 100) Phase 1/Phase 2 Interventional Amgen In this study, encouraging antitumour activity was demonstrated in heavily pretreated advanced KRASG12C-mutated solid cancers. 1