| Identification | Back Directory | [Name]
2-Propen-1-one, 1-[(3S)-4-[(7R)-7-[6-amino-4-methyl-3-(trifluoromethyl)-2-pyridinyl]-6-chloro-8-fluoro-2-[[(2S)-1-methyl-2-pyrrolidinyl]methoxy]-4-quinazolinyl]-3-methyl-1-piperazinyl]- | [CAS]
2417987-45-0 | [Synonyms]
GDC-6036
divarasib
2-Propen-1-one, 1-[(3S)-4-[(7R)-7-[6-amino-4-methyl-3-(trifluoromethyl)-2-pyridinyl]-6-chloro-8-fluoro-2-[[(2S)-1-methyl-2-pyrrolidinyl]methoxy]-4-quinazolinyl]-3-methyl-1-piperazinyl]- | [Molecular Formula]
C29H32ClF4N7O2 | [MOL File]
2417987-45-0.mol | [Molecular Weight]
622.06 |
| Chemical Properties | Back Directory | [Boiling point ]
743.4±70.0 °C(Predicted) | [density ]
1.344±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: Soluble: =10 mg/ml
Ethanol: Slightly soluble: 0.1-1 mg/ml | [form ]
Solid | [pka]
9.13±0.40(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
Divarasib (GDC-6036) is an orally bioavailable, highly potent, and selective KRAS G12C inhibitor with an IC50 of <0.01 μM. Divarasib covalently binds to the switch II (SW-II) pocket of KRAS G12C and irreversibly locks it in the inactive GDP-bound state. | [in vivo]
Divarasib (10-100 mg/kg/day; PO for 7 days) decreases the ratio of free KRAS G12C[1]. | Animal Model: | Female C.B-17 SCID (Inbred) mice (20-21 weeks old; 24.1 g) with human NSCLC NCI-H2030.X1.1 cells[1] | | Dosage: | 10, 25, or 100 mg/kg | | Administration: | Oral gavage (PO) every day (QD) for 7 days (vehicle: 0.5% methylcellulose) | | Result: | Decreased the ratio of free KRAS G12C to internal standard.
Dose-dependent target engagement was observed for all time points (2, 8, and 24 h post-last dose), with over 90% KRAS G12C engagement observed for the highest dose 100 mg/kg assessed.
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| [IC 50]
K-Ras(G12C): <0.01 μM (IC50) | [storage]
Store at -20°C | [References]
[1] Lingyao Meng, et al. Assessment of KRAS G12C Target Engagement by a Covalent Inhibitor in Tumor Biopsies Using an Ultra-Sensitive Immunoaffinity 2D-LC-MS/MS Approach. Anal Chem. 2022 Sep 20;94(37):12927-12933. DOI:10.1021/acs.analchem.2c03146
[2] Sushant Malhotra, et al. Fused ring compounds. WO2020097537A2. |
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