SOS1-IN-26
SOS1-IN-26 is a potent, orally active selective allosteric SOS1 inhibitor with a KD of 33 nM and SOS1-KRAS binding IC50 of 4.0 nM. SOS1-IN-26 disrupts SOS1-KRAS interaction, inhibits MAPK/PI3K signaling, induces G1 phase arrest and tumor cell apoptosis. SOS1-IN-26 serves as a balanced lead therapeutic candidate for pan-KRAS-driven colorectal cancer studies.
For research use only. We do not sell to patients.
- Formula: C31H40N4O
- Molecular Weight:484.68
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
|
p38 MAPK |
SOS1 33 nM (Kd) |
SOS1-KRAS 4 nM (IC50) |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| SW-620 | IC50 |
0.65 μM
|
Inhibits SW-620 cells growth for 120 h
Inhibits SW-620 cells growth for 120 h
|
42247371 |
| HT-29 | IC50 |
0.89 μM
|
Inhibits HT-29 cells growth for 120 h
Inhibits HT-29 cells growth for 120 h
|
42247371 |
| SW837 | IC50 |
1.1 μM
|
Inhibits SW837 cells growth for 120 h
Inhibits SW837 cells growth for 120 h
|
42247371 |
| HCT-116 | IC50 |
0.97 μM
|
Inhibits HCT-116 cells growth for 120 h
Inhibits HCT-116 cells growth for 120 h
|
42247371 |
| SW480 | IC50 |
0.82 μM
|
Inhibits SW480 cells growth for 120 h
Inhibits SW480 cells growth for 120 h
|
42247371 |
| RKO | IC50 |
0.92 μM
|
Inhibits RKO cells growth for 120 h
Inhibits RKO cells growth for 120 h
|
42247371 |
| GP2D cell | IC50 |
0.38 μM
|
Inhibits GP2D cells growth for 120 h
Inhibits GP2D cells growth for 120 h
|
42247371 |
SOS1-IN-26 (78b) potently blocks SOScat-catalyzed nucleotide exchange of G12V and G12D mutant KRAS with IC50 values of 24 nM (G12V) and 20 nM (G12D), while barely suppressing EGFR activity at 1 μM and thus displaying favorable EGFR kinase selectivity[1].
SOS1-IN-26 (10 μM; 40 min) markedly elevates the thermal stability of SOScat[1].
SOS1-IN-26 binds SOS1 to break SOS1-KRAS interaction, showing reduced fluorescence polarization (FP=84 mP) and robust SOS1-KRASG12C binding inhibition (IC50=4.0 nM)[1].
SOS1-IN-26 (120 h) exerts strong inhibitory activity across all tested CRC cell lines (IC50 of 93-321 nM) in 3D cell culture, with stronger potency than that observed in 2D cell culture[1].
SOS1-IN-26 (1 μM; 0-60 min) exhibits moderate intrinsic clearance (CLint=19.06 mL/min/kg) and a T1/2 of 91.18 min in human liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
SOS1-IN-26 (500 mg/kg; p.o.; single dose) possesses high tolerable doses and favorable safety profiles in Balb/c mice[1].
SOS1-IN-26 (30-60 mg/kg; p.o.; 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.
-
Animal Model:Female Balb/c nude mice (6-8 weeks, 20-22 g)[1]
-
Dosage:50 mg/kg
-
Administration:p.o.; single dose
-
Result:Accumulated at high levels in the stomach, gastrointestinal tract, and lungs.
Reached a peak intestinal concentration of 139822 ng/g at 2.0 h.
-
Animal Model:Female Balb/c mice (6-8 weeks, 20-25 g)[1]
-
Dosage:500 mg/kg
-
Administration:p.o.; single dose
-
Result:Had no significant effect on the body weight of mice.
Did not alter blood biochemical parameters.
-
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].
-
Dosage:30 mg/kg, 60 mg/kg
-
Administration:p.o.; once daily; for 18 days
-
Result:Dose-dependently suppressed HCT116 xenograft tumor volume, with tumor growth inhibition (TGI) values of 67.9% at 30 mg/kg and 75.1% 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
-
Molecular Weight 484.68
-
Formula C31H40N4O
-
SMILES
C[C@@H](NC1=NC(OC)=NC2=CC=C(C=C21)N3CCCC3)C4=CC=C(C=C4)C5=CC(C)(CC(C)(C5)C)C
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SOS1-IN-26 Related Classifications
HY-184422 Related Classifications
Powered by Bioz