Chemistry:AMG 510
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| Formula | C30H30F2N6O3 |
| Molar mass | 560.606 g·mol−1 |
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AMG 510 is an experimental cancer drug. It targets a specific mutation, G12C, in the protein KRAS which is responsible for various forms of cancer.[1][2]
Clinical development
AMG 510 is being developed by Amgen and, as of 2019, it was in Phase 1 clinical trials.[3][4] In December, it was approved to begin Phase 2 clinical trials.[5]
Because the G12C KRAS mutation is relatively common in some cancer types, 14% of non-small-cell lung cancer adenocarcinoma patients and 5% of colorectal cancer patients,[6] and AMG 510 is the first drug candidate to target this mutation, there have been high expectations for the drug.[6][7][8] The Food and Drug Administration has granted a fast track designation to AMG 510 for the treatment of metastatic non-small-cell lung carcinoma with the G12C KRAS mutation.[9]
Chemistry and pharmacology
AMG 510 can exist in either of two atropisomeric forms and one is more active than the other.[6] It selectively forms an irreversible covalent bond to the sulfur atom in the cysteine residue that is present in the mutated form of KRAS, but not in the normal form.[6]
References
- ↑ "KRAS mutant-targeting AMG 510". NCI Drug Dictionary. National Cancer Institute. 2011-02-02. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/794411.
- ↑ "The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity". Nature 575 (7781): 217–223. November 2019. doi:10.1038/s41586-019-1694-1. PMID 31666701. Bibcode: 2019Natur.575..217C.
- ↑ Clinical trial number NCT03600883 for "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 " at ClinicalTrials.gov
- ↑ "The Discovery Of Amgen's Novel Investigational KRAS(G12C) Inhibitor AMG 510 Published In Nature" (Press release). Amgen. October 30, 2019. Retrieved November 16, 2019.
- ↑ Irving, Michael (2019-12-24). "Drug targeting common cancer cause enters phase 2 clinical trials". https://newatlas.com/medical/common-cancer-cause-drug-phase2-clinical-trials/.
- ↑ 6.0 6.1 6.2 6.3 Halford, Bethany (April 3, 2019). "Amgen unveils its KRas inhibitor in human clinical trials: AMG 510 shuts down a mutant version of the cancer target via covalent interaction". Chemical & Engineering News 97 (4). https://cen.acs.org/pharmaceuticals/drug-discovery/Amgen-unveils-KRas-inhibitor-human/97/i14. Retrieved November 16, 2019.
- ↑ Al Idrus, Amirah (September 9, 2019). "Amgen's KRAS drug continues to deliver but faces 'curse' of high expectations". fiercebiotech.com. https://www.fiercebiotech.com/biotech/amgen-s-kras-drug-continues-to-deliver-but-faces-curse-high-expectations.
- ↑ Kaiser, Jocelyn (2019-10-30). "Two new drugs finally hit 'undruggable' cancer target, providing hope for treatments". Science Magazine. AAAS. https://www.sciencemag.org/news/2019/10/two-new-drugs-finally-hit-undruggable-cancer-target-providing-hope-treatments.
- ↑ Astor, Lisa (September 9, 2019). "FDA Grants AMG 510 Fast Track Designation for KRAS G12C+ NSCLC". targetedonc.com. https://www.targetedonc.com/news/fda-grants-amg-510-fast-track-designation-for-kras-g12c-nsclc.
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