SL43
SL43 is an orally active and potent SOS1 inhibitor with a Kd of 0.16 μM. SL43 disrupts SOS1-KRAS interaction, inhibits SOS1-mediated nucleotide exchange on KRAS mutants, and suppresses RAS-MAPK signaling. SL43 exerts antiproliferative activity against KRAS-mutant cancer cells, induces early apoptosis and G1 phase cell cycle arrest, and reduces phosphorylated MEK and ERK levels. SL43 suppresses tumor growth in a colorectal cancer xenograft model.
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- Fòrmula: C27H33ClN4
- Peso molecular:449.03
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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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K-RAS |
SL43 binds to SOScat with a Kd of 0.16 μM, indicating high affinity for the SOS1 catalytic domain[1].
SL43 potently disrupts the SOS1-KRASG12C interaction with an IC50 of 13.0 nM[1].
SL43 preferentially inhibits SOS1-mediated nucleotide exchange on KRASG12C, KRASG12V, and KRASG12D mutants with IC50 values ranging from 13.4-29.1 nM, while showing weaker inhibition of KRASWT (IC50 = 95.8 nM)[1].
SL43 (120 h) potently and selectively inhibits the proliferation of KRAS-mutant CRC cell lines (IC50 = 0.028-0.238 μM) with over 100-fold selectivity over KRAS wild-type CRC cell lines (IC50 = 2.495-4.520 μM)[1].
SL43 (10-40 nM; 72 h) dose-dependently suppresses colony formation in SW620 and HCT116 KRAS-mutant CRC cell lines[1].
SL43 (200-800 nM; 48 h) dose-dependently induces early apoptosis and G1 phase cell cycle arrest in SW620 and HCT116 KRAS-mutant CRC cell lines[1].
SL43 (50-200 nM; 48 h) dose-dependently inhibits the RAS-MAPK signaling pathway in SW620 and HCT116 KRASG12D/G13D CRC cell lines by reducing phosphorylated MEK and ERK levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KRAS-mutant CRC cell lines (SW620/G12V, HCT116/G13D)
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Concentration:200, 400, 800 nM
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Incubation Time:48 h
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Result:Significantly increased the proportion of early apoptotic cells, with high-concentration groups reaching 35.47% in SW620 cells and 25.97% in HCT116 cells.
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Cell Line:KRAS-mutant CRC cell lines (SW620/G12V, HCT116/G13D)
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Concentration:200, 400, 800 nM
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Incubation Time:48 h
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Result:Induced dose-dependent G1 phase cell cycle arrest, with the G1 population increasing from 64.13% to 78.04% in SW620 cells and from 35.34% to 57.59% in HCT116 cells.
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Cell Line:KRAS-mutant CRC cell lines (SW620/G12V, HCT116/G13D)
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Concentration:50, 100, 200 nM
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Incubation Time:48 h
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Result:Led to a concentration-dependent decrease in p-MEK and p-ERK levels in both SW620 and HCT116 cells.
Left total MEK and ERK expression unaltered.
SL43 (400-800 mg/kg; p.o.; single dose) has a favorable safety profile in BALB/c mice, with an estimated oral median lethal dose (LD50) exceeding 800 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Colorectal cancer BALB/c nude mice (female, 6-8 weeks old, 20-22 g, subcutaneous inoculation of HCT116 KRASG13D cells)[1]
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Dosage:20 mg/kg; 40 mg/kg
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Administration:p.o.; daily; 18 days
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Result:Produced a tumor growth inhibition (TGI) rate of 57.2% at 20 mg/kg.
Produced a tumor growth inhibition (TGI) rate of 74.9% at 40 mg/kg.
Induced no significant body weight loss or observable histological alterations in major organs (heart, liver, spleen, lungs, kidneys) at either dose.
Chemical Information
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Peso molecular 449.03
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Fòrmula C27H33ClN4
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SMILES
ClC1=CC=C([C@@H](C)NC2=NC(NCC(C)(C)C)=NC3=CC=C(C4=CCCCC4)C=C23)C=C1
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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)
SL43 Related Classifications
HY-183365 Related Classifications
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