AMG 510 Chemical Properties

Boiling point:

730.5±70.0 °C(Predicted)

Density 

1.36±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C, stored under nitrogen

solubility 

DMSO:75.0(Max Conc. mg/mL);133.78(Max Conc. mM)
Water:33.33(Max Conc. mg/mL);59.45(Max Conc. mM)
Ethanol:8.0(Max Conc. mg/mL);14.27(Max Conc. mM)

form 

Solid

pka

6.52±0.35(Predicted)

color 

Light yellow to yellow

AMG 510 Usage And Synthesis

Description

AMG-510 is a first-in-class, orally bioavailable, and selective KRAS G12C covalent inhibitor. AMG-510 irreversibly inhibits KRAS G12C by locking it in an inactive GDP-bound state. AMG-510 is the first KRAS G12C inhibitor in clinical development and leads to the regression of KRAS G12C tumors.

Biological Activity

AMG-510 is a potent, orally bioavailable, and selective KRAS G12C covalent inhibitor with anti-tumor activity.
AMG-510, also known as also known as Sotorasib, is a potent KRAS G12C covalent inhibitor and the active atropisomer separated by chiral HPLC. AMG-510 selectively targets the KRAS p.G12C mutant, at either the DNA, RNA or protein level, and prevents, through an as of yet not elucidated manner, expression of and/or tumor cell signaling through the KRAS p.G12C mutant. This may inhibit growth in KRAS p.G12C-expressing tumor cells.

Storage

-20°C, stored under nitrogen

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. Reference: Nature. 2019 Nov;575(7781):217-223. https://www.nature.com/articles/s41586-019-1694-1

Uses

AMG-510 is a KRAS G12C inhibitor thus leading to the regression of KRAS G12C tumors as it interrupts protein signaling.

Definition

ChEBI: Sotorasib is a pyridopyrimidine that is pyrido[2,3-d]pyrimidin-2(1H)-one substituted by 4-methyl-2-(propan-2-yl)pyridin-3-yl, (2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl, fluoro and 2-fluoro-6-hydroxyphenyl groups at positions 1, 4, 6 and 7, respectively. It is approved for the treatment of patients with non-small cell lung cancer having KRAS(G12C) mutations. It has a role as an antineoplastic agent. It is a member of acrylamides, a N-acylpiperazine, a pyridopyrimidine, a member of monofluorobenzenes, a member of methylpyridines, a tertiary carboxamide, a tertiary amino compound and a member of phenols.

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). Reference: Mol Clin Oncol. 2021 Jul;15(1):148.

storage

Store at -20°C

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