| Identification | Back Directory | [Name]
Cyclopropanecarbonitrile, 1-[[(4aR)-11-[[(1R)-1-[3-(difluoromethyl)-2-fluorophenyl]ethyl]amino]-1,2,4a,5-tetrahydro-9-methylpyrazino[2,1-c]pyrimido[5,4-g][1,4]benzoxazin-3(4H)-yl]carbonyl]- | [CAS]
2793404-47-2 | [Synonyms]
Cyclopropanecarbonitrile, 1-[[(4aR)-11-[[(1R)-1-[3-(difluoromethyl)-2-fluorophenyl]ethyl]amino]-1,2,4a,5-tetrahydro-9-methylpyrazino[2,1-c]pyrimido[5,4-g][1,4]benzoxazin-3(4H)-yl]carbonyl]- | [Molecular Formula]
C28H27F3N6O2 | [MOL File]
2793404-47-2.mol | [Molecular Weight]
536.55 |
| Chemical Properties | Back Directory | [Boiling point ]
641.8±55.0 °C(Predicted) | [density ]
1.44±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
6?+-.0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
SOS1-IN-15 (Compound 37) is an orally active SOS1 inhibitor with an IC50 of 5 nM. SOS1-IN-15 is a promising agent candidate for the research of KRAS-driven cancer[1]. | [in vivo]
SOS1-IN-15 (Compound 37) (50 mg/kg; p.o.; daily for 22 days) inhibits tumor volume in mice[1]. | Animal Model: | BALB/c nude mice bearing Mia-paca-2 pancreas tumors[1] | | Dosage: | 50 mg/kg | | Administration: | Oral administration, daily for 22 days | | Result: | Showed 49% tumor inhibition. No animal mortality and significant difference in the mice’s body weight were observed during the study period. |
| Animal Model: | Male CD-1 Mice[1] | | Dosage: | 20 mg/kg | | Administration: | Oral administration (Pharmacokinetic Analysis) | | Result: | In Vivo Pharmacokinetic Properties of the Compounds in Male CD-1 Micea
| T1/2 (h) | Tmax (h) | Cmax (ng/mL) | AUC (ng?h/mL) | MRT (h) | Kel (h-1) | | SOS1-IN-15 | 11.4 | 3.67 | 1550 | 9900 | 4.19 | 0.25 |
aCompounds (20 mg/kg) were P.O. dosed in a mixture of 63% water + 30% PEG +5 % DMSO + 2% Tween 80 in male ICR mice (n = 3). Abbreviations: T1/2, elimination half-life; Tmax, plasma peak time after administration; Cmax, maximum plasma concentration; AUC, area under concentration-time curve. MRT, mean residence time; Kel, elimination rate constant.
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| [IC 50]
SOS1: 5 nM (IC50) | [References]
[1] Zhang S, et al. Design and Structural Optimization of Orally Bioavailable SOS1 Inhibitors for the Treatment of KRAS-Driven Carcinoma. J Med Chem. 2022 Nov 17. DOI:10.1021/acs.jmedchem.2c01517 |
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