Sotorasib

Sotorasib (AMG510) is a potent KRAS G12C covalent inhibitor with potential antineoplastic activity.

Product information

CAS Number: 2296729-00-3

Molecular Weight: 560.59

Formula: C30H30F2N6O3

Synonym:

AMG-510

Chemical Name: 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[2-methyl-4-(prop-2-enoyl)piperazin-1-yl]-1H, 2H-pyrido[2, 3-d]pyrimidin-2-one, (1R)

Smiles: CC1=CC=NC(C(C)C)=C1N1C2=NC(C3=C(O)C=CC=C3F)=C(F)C=C2C(=NC1=O)N1CCN(CC1C)C(=O)C=C

InChiKey: NXQKSXLFSAEQCZ-UHFFFAOYSA-N

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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO:100 mg/mL (178.38 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

It was examined whether AMG510 has an antitumor effect on the CACO-2 (human colorectal cancer) cells into which the KRAS G12C (Kirsten rat sarcoma 2 viral oncogene homolog mutation) gene was introduced. The results showed that there was a clear concentration dependent RPR (relative proliferation ratio) decrease and that AMG 510 selectively inhibited KRAS G12C in colon cancer cells in vitro (Fig. 4A).

In Vivo:

In immune-competent mice, treatment with AMG 510 resulted in a pro-inflammatory tumour microenvironment and produced durable cures alone as well as in combination with immune-checkpoint inhibitors. Cured mice rejected the growth of isogenic KRASG12D tumours, which suggests adaptive immunity against shared antigens.

References:

1. Ryan MB, Fece de la Cruz F, Phat S, Myers DT, Wong E, Shahzade HA, Hong CB, Corcoran RB. Vertical pathway inhibition overcomes adaptive feedback resistance to KRASG12C inhibition. Clin Cancer Res. 2019 Nov 27. pii: clincanres.3523.2019. doi: 10.1158/1078-0432.CCR-19-3523. [Epub ahead of print] PubMed PMID: 31776128.
2. Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30. PubMed PMID: 31666701.
3. AMG 510 First to Inhibit "Undruggable" KRAS. Cancer Discov. 2019 Aug;9(8):988-989. doi: 10.1158/2159-8290.CD-NB2019-073. Epub 2019 Jun 12. PubMed PMID: 31189530.

Products are for research use only. Not for human use.