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.
2D Structure
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Physico-chemical Properties
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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
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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
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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