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]-
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]- Basic information
- Product 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]-
- Synonyms:
-
- 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]-
- GDC-6036
- divarasib
- GDC-6036(Divarasib)
- 1-((S)-4-(7-((R)-6-Amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-chloro-8-fluoro-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)quinazolin-4-yl)-3-methylpiperazin-1-yl)prop-2-en-1-one
- CAS:
- 2417987-45-0
- MF:
- C29H32ClF4N7O2
- MW:
- 622.06
- Product Categories:
-
- api
- GDC-6036
- Mol File:
- 2417987-45-0.mol
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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]- Chemical Properties
- Boiling point:
- 743.4±70.0 °C(Predicted)
- Density
- 1.344±0.06 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- form
- Solid
- pka
- 9.13±0.40(Predicted)
- color
- White to light yellow
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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]- Usage And Synthesis
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. |
IC 50
K-Ras(G12C): <0.01 μM (IC50)
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.
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]-Supplier
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