Sotorasib 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 : 100 mg/mL (178.38 mM; Need ultrasonic)|

pka

6.52±0.35(Predicted)

Water Solubility 

Water : 33.33 mg/mL (59.46 mM; ultrasonic and adjust pH to 11 with NaOH)

InChIKey

NXQKSXLFSAEQCZ-UHFFFAOYSA-N

SMILES

O=C1N=C(N2CCN(C(=O)C=C)CC2C)C2=CC(F)=C(C3C(=CC=CC=3F)O)N=C2N1C1C(=CC=NC=1C(C)C)C

Sotorasib Usage And Synthesis

Description

Sotorasib (AMG510) is a chiral compound and a potent KRAS G12C covalent inhibitor with potential antitumor activity.

Uses

Sotorasib (AMG510) is the first KRAS (G12C) inhibitor to enter clinical development. Having shown antitumor activity in clinical trials, AMG 510 represents a potentially transformative therapy.

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.

General Description

Sotorasib, also known as AMG-510, is an acrylamide derived KRAS inhibitor developed by Amgen. It is indicated in the treatment of adult patients with KRAS G12C mutant non small cell lung cancer. This mutation makes up >50% of all KRAS mutations. Mutant KRAS discovered in 1982 but was not considered a druggable target until the mid-2010s. It is the first experimental KRAS inhibitor. The drug [MRTX849] is also currently being developed and has the same target. Sotorasib was granted FDA approval on 28 May 2021.

Side effects

Sotorasib may cause breathing problems that could lead to death. Get emergency medical help if you have new or worsening fever, cough, or shortness of breath.
Common side effects may include:
nausea, diarrhea;
cough;
liver problems;
pain in your bones, joints, or muscles;
tiredness;
abnormal lab tests.
For 28 patients (22%), side effects led to a pause, a reduction, or both, in the dose of sotorasib. Nine people (7%) stopped the treatment because of side effects.
www.everydayhealth.com/drugs/sotorasib

Mode of action

Sotorasib is an orally available inhibitor of the specific KRAS mutation, p.G12C, with potential antineoplastic activity. Upon oral administration, sotorasib selectively targets, binds to and inhibits the activity of the KRAS p.G12C mutant. This may inhibit growth in KRAS p.G12C-expressing tumor cells. The KRAS p.G12C mutation is seen in some tumor cell types and plays a key role in tumor cell proliferation.

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