| Identification | Back Directory | [Name]
ARS-1620 | [CAS]
1698055-85-4 | [Synonyms]
CPD1588
ARS-1620
ARS-1620;ARS 1620;ARS1620
(S)-1-(4-(6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)prop-2-en-1-one
2-Propen-1-one, 1-[4-[(7S)-6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)-4-quinazolinyl]-1-piperazinyl]-
1-?[4-?[(7S)?-?6-?Chloro-?8-?fluoro-?7-?(2-?fluoro-?6-?hydroxyphenyl)?-?4-?quinazolinyl]?-?1-?piperazinyl]?-?2-?propen-?1-?one | [Molecular Formula]
C21H17ClF2N4O2 | [MDL Number]
MFCD31619312 | [MOL File]
1698055-85-4.mol | [Molecular Weight]
430.84 |
| Chemical Properties | Back Directory | [Boiling point ]
614.7±55.0 °C(Predicted) | [density ]
1.434±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:70.0(Max Conc. mg/mL);162.47(Max Conc. mM) | [form ]
A solid | [pka]
6.03±0.35(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
ARS-1620, is an atropisomeric selective KRASG12C inhibitor with desirable pharmacokinetics. | [Definition]
ChEBI: ARS-1620 is a qinazoline derivative carrying chloro and fluoro substituents at positions 6 and 8 respectively, a 2-fluoro-6-hydroxyphenyl group at position 7, and a 4-(prop-2-enoyl)piperazin-1-yl group at position 4. A potent, selective, and orally bioavailable covalent KRAS-G12C inhibitor, it inhibits the protein coding gene KRAS (Kirsten rat sarcoma virus) with high potency in cells and animals. It has a role as an inhibitor, an antiviral agent and an antineoplastic agent. | [in vivo]
Following a single oral dose or 5 consecutive daily doses, ARS-1620 yields average peak tumor concentrations of 1.5 μM (50 mg/kg) and 5.5 μM (200 mg/kg), respectively, that enables significant KRASG12C target occupancy (>=70% G12C-TE at 200 mg/kg) for >24 hr. In MIAPaCa2 xenografts (p.G12C), ARS-1620 significantly inhibits tumor growth (p<0.001) in a dose-dependent manner with marked regression at a dose of 200 mg/kg, given once daily. Across all tumor models employed, ARS-1620 is well tolerated over the entire 3-week treatment period. Moreover, there are no observed clinical signs or toxicity of ARS-1620 in CD-1 mice even at oral doses up to 1,000 mg/kg administered daily over a 7-day period. | [IC 50]
KRAS(G12C) | [storage]
Store at -20°C |
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