2. MAPK/ERK Pathway GPCR/G Protein Stem Cell/Wnt Apoptosis
  3. SOS1 Ras p38 MAPK ERK MEK Apoptosis
  4. 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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SL43

SL43 Chemical Structure

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SL43 Related Antibodies

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Description

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[1].

IC50 & Target[1]

K-RAS

 

In Vitro

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.

SL43 Related Antibodies

Apoptosis Analysis[1]

Cell Line: KRAS-mutant CRC cell lines (SW620/G12V, HCT116/G13D)
Concentration: 200, 400, 800 nM
Incubation Time: 48 h
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.

Cell Cycle Analysis[1]

Cell Line: KRAS-mutant CRC cell lines (SW620/G12V, HCT116/G13D)
Concentration: 200, 400, 800 nM
Incubation Time: 48 h
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.

Western Blot Analysis[1]

Cell Line: KRAS-mutant CRC cell lines (SW620/G12V, HCT116/G13D)
Concentration: 50, 100, 200 nM
Incubation Time: 48 h
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.
Parmacokinetics
Species Dose Route AUC0-t Tmax T1/2 Cmax F
Mice[1] 20 mg/kg i.v. 6504.1 ng·h/mL 0.1 h 4.2 h 3649.1 ng/mL /
Mice[1] 20 mg/kg p.o. 3697.2 ng·h/mL 2.0 h 4.6 h 468.2 ng/mL 56.8 %
In Vivo

SL43 (20-40 mg/kg; i.g.; daily; 18 days) exerts potent dose-dependent antitumor efficacy in KRAS-mutant colorectal cancer xenografts, achieving a maximum TGI of 74.9% at 40 mg/kg with no detectable systemic toxicity[1].
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.

Animal Model: Colorectal cancer BALB/c nude mice (female, 6-8 weeks old, 20-22 g, subcutaneous inoculation of HCT116 KRASG13D cells)[1]
Dosage: 20 mg/kg; 40 mg/kg
Administration: p.o.; daily; 18 days
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.
Molecular Weight

449.03

Formula

C27H33ClN4
SMILES

ClC1=CC=C([C@@H](C)NC2=NC(NCC(C)(C)C)=NC3=CC=C(C4=CCCCC4)C=C23)C=C1
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
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SL43 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SL43SL 43SL-43SOS1Rasp38 MAPKERKMEKApoptosisRas/Rac guanine nucleotide exchange factor 1Extracellular signal regulated kinasesMitogen-activated protein kinase kinaseMAPKKMAP2Kcolorectal cancer xenograft modelKRAS mutantsKRASG12CKRAScolorectal cancer cellsKRASG12VmiceKRASG12DSOScatInhibitorinhibitorinhibit

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