SOS1-IN-27
SOS1-IN-27 is a potent, selective allosteric SOS1 inhibitor with a KD of 14 nM and SOS1-KRAS binding IC50 of 1.6 nM. SOS1-IN-27 disrupts SOS1-KRAS interaction, inhibits MAPK/PI3K signaling, induces G1 arrest and tumor cell apoptosis. SOS1-IN-27 serves as a valuable tool compound for pan-KRAS-driven colorectal cancer studies.
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- Fòrmula: C32H43N5
- Peso molecular:497.72
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
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p38 MAPK |
SOS1 14 nM (Kd) |
SOS1-KRAS 1.6 nM (IC50) |
PI3K |
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Cell Line
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Type | Value | Description | References |
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| SW-620 | IC50 |
0.68 μM
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Inhibits SW-620 cells growth for 120 h
Inhibits SW-620 cells growth for 120 h
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42247371 |
| SW837 | IC50 |
0.5 μM
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Inhibits SW837 cells growth for 120 h
Inhibits SW837 cells growth for 120 h
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42247371 |
| GP2D cell | IC50 |
0.2 μM
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Inhibits GP2D cells growth for 120 h
Inhibits GP2D cells growth for 120 h
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42247371 |
| HCT-116 | IC50 |
0.47 μM
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Inhibits HT-116 cells growth for 120 h
Inhibits HT-116 cells growth for 120 h
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42247371 |
| SW480 | IC50 |
0.52 μM
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Inhibits SW480 cells growth for 120 h
Inhibits SW480 cells growth for 120 h
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42247371 |
| HT-29 | IC50 |
0.56 μM
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Inhibits HT-29 cells growth for 120 h
Inhibits HT-29 cells growth for 120 h
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42247371 |
| RKO | IC50 |
0.31 μM
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Inhibits RKO cells growth for 120 h
Inhibits RKO cells growth for 120 h
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42247371 |
SOS1-IN-27 (78d) potently blocks SOScat-catalyzed nucleotide exchange of wild-type and mutant KRAS with IC50 values of 11 nM (wild-type), 7.0 nM (G12C), 8.1 nM (G12V), and 17 nM (G12D), while exhibiting negligible EGFR inhibitory activity even at 1 μM and thus demonstrating outstanding EGFR kinase selectivity[1].
SOS1-IN-27 (10 μM; 40 min) significantly improves the thermal stability of SOScat[1].
SOS1-IN-27 binds SOS1 to disrupt SOS1-KRAS interaction, showing reduced fluorescence polarization (FP=83 mP) and potent SOS1-KRASG12C binding inhibition (IC50=1.6 nM)[1].
SOS1-IN-27 (120 h) demonstrates potent inhibitory activity across all tested CRC cell lines (IC50 of 93-321 nM) in 3D cell culture, which is stronger than that in 2D cell culture[1].
SOS1-IN-27 (0.2-0.8 μM; 14 days) effectively inhibits the clonogenicity of SW620 and HCT116 cells[1].
SOS1-IN-27 (2-8 μM; 48 h) induces apoptosis and G1-phase cell cycle arrest in SW620 and HCT116 cells[1].
SOS1-IN-27 (0.5-2 μM; 72 h) modulates the expression of critical cell cycle regulatory proteins in SW620 and HCT116 cells[1].
SOS1-IN-27 (0.5-2 μM; 72 h) reduces the levels of key proteins in MAPK and PI3K signaling pathways in SW620 and HCT116 cells[1].
SOS1-IN-27 (1 μM; 0-60 min) exhibits moderate intrinsic clearance (CLint=36.12 mL/min/kg) and a T1/2 of 48.13 min in human liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SW620 and HCT116 cells
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Concentration:0.2 μM, 0.4 μM, 0.8 μM
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Incubation Time:14 days
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Result:Reduced the number of colonies in a concentration-dependent manner.
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Cell Line:SW620 and HCT116 cells
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Concentration:2 μM, 4 μM, 8 μM
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Incubation Time:48 h
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Result:Significantly increased the proportion of annexin-V-positive cells in a concentration-dependent manner.
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Cell Line:SW620 and HCT116 cells
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Concentration:2 μM, 4 μM, 8 μM
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Incubation Time:48 h
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Result:Resulted in a concentration-dependent increase in the proportion of cells in the G1 phase.
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Cell Line:SW620 and HCT116 cells
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Concentration:0.5 μM, 1 μM, 2μM
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Incubation Time:72 h
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Result:Reduced cyclin D1 protein levels.
Resulted in a concentration-dependent reduction in the phosphorylation of CRAF, MEK, and ERK in the two cell lines.
Reduced p-AKT protein levels.
SOS1-IN-27 (700 mg/kg; p.o.; single dose) possesses high tolerable doses and favorable safety profiles in Balb/c mice[1].
SOS1-IN-27 (30-60 mg/kg; i.p.; once daily; for 18 days) inhibits tumor growth and demonstrates a good safety profile in HCT116 xenograft models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female Balb/c nude mice (6-8 weeks, 20-22 g)[1]
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Dosage:50 mg/kg
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Administration:p.o.; single dose
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Result:Accumulated primarily in the stomach and intestine.
Reached a peak intestinal concentration of 81802 ng/g at 4.0 h.
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Animal Model:Female Balb/c mice (6-8 weeks, 20-25 g)[1]
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Dosage:700 mg/kg
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Administration:p.o.; single dose
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Result:Had no significant effect on the body weight of mice.
Did not alter blood biochemical parameters.
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Animal Model:Female Balb/c nude mice (6-8 weeks, 18-22 g) were subcutaneously inoculated with HCT116 cells (5 × 106 cells per mouse)[1].
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Dosage:30 mg/kg, 60 mg/kg
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Administration:i.p.; once daily; for 18 days
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Result:Dose-dependently suppressed HCT116 xenograft tumor volume, with tumor growth inhibition (TGI) values of 71.6% at 30 mg/kg and 84.2% at 60 mg/kg.
Selectively downregulated intratumoral p-ERK levels without obvious p-ERK suppression in normal stomach, liver and lung tissues of tumor-bearing mice.
Chemical Information
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Peso molecular 497.72
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Fòrmula C32H43N5
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SMILES
C[C@@H](NC1=NC(N(C)C)=NC2=CC=C(C=C21)N3CCCC3)C4=CC=C(C=C4)C5=CC(C)(CC(C)(C5)C)C
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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