| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
The Kd value of SL43 to SOScat is 0.16 μM, indicating that it has a high affinity for the SOS1 catalytic domain [1]. SL43 can effectively disrupt the interaction between SOS1 and KRASG12C, with an IC50 value 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 to 29.1 nM, while its inhibitory effect on KRASWT is weak (IC50 = 95.8 nM) [1]. SL43 (120 h) potently and selectively inhibited the proliferation of KRAS mutant CRC cell lines (IC50 = 0.028-0.238 μM), and its inhibitory selectivity against KRAS wild-type CRC cell lines was more than 100-fold higher than that against KRAS wild-type CRC cell lines (IC50 = 2.495-4.520 μM) [1]. SL43 (10-40 nM; 72 h) dose-dependently inhibited the colony formation of SW620 and HCT116 KRAS mutant CRC cell lines [1]. SL43 (200-800 nM; 48 h) dose-dependently induced early apoptosis and G1 phase cell cycle arrest in SW620 and HCT116 KRAS mutant CRC cell lines [1]. SL43 (50–200 nM; 48 h) inhibited the RAS-MAPK signaling pathway in SW620 and HCT116 KRASG12D/G13D CRC cell lines in a dose-dependent manner by reducing phosphorylated MEK and ERK levels [1].
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|---|---|
| ln Vivo |
SL43 (20-40 mg/kg; gavage; once daily; for 18 days) showed potent dose-dependent antitumor efficacy in KRAS-mutant colorectal cancer xenografts, with a tumor growth inhibition rate (TGI) of up to 74.9% at a dose of 40 mg/kg, and no systemic toxicity was detected [1]. SL43 (400-800 mg/kg; oral; single dose) showed good safety in BALB/c mice, with an estimated oral median lethal dose (LD50) exceeding 800 mg/kg [1].
|
| Cell Assay |
Apoptosis analysis [1]
Cell Types: KRAS mutant CRC cell lines (SW620/G12V, HCT116/G13D) Tested Concentrations: 200, 400, 800 nM Incubation Duration: 48 h Experimental Results: Significantly increased the proportion of early apoptotic cells, with the high concentration group reaching 35.47% in SW620 cells and 25.97% in HCT116 cells. Cell cycle analysis [1] Cell Types: KRAS mutant CRC cell lines (SW620/G12V, HCT116/G13D) Tested Concentrations: 200, 400, 800 nM Incubation Duration: 48 h Experimental Results: Dose-dependent G1 phase cell cycle arrest was induced. The proportion of G1 phase cells in SW620 cells increased from 64.13% to 78.04%, and the proportion of G1 phase cells in HCT116 cells increased from 35.34% to 57.59%. Western Blot Analysis [1] Cell Types: KRAS mutant CRC cell lines (SW620/G12V, HCT116/G13D) Tested Concentrations: 50, 100, 200 nM Incubation Duration: 48 hours Experimental Results: The levels of p-MEK and p-ERK in SW620 and HCT116 cells decreased in a concentration-dependent manner. The total expression levels of MEK and ERK remained unchanged. |
| Animal Protocol |
Animal/Disease Models:Colorectal cancer BALB/c nude mice (female, 6-8 weeks old, 20-22 g, subcutaneously inoculated with HCT116 KRASG13D cells)[1]
Doses: 20 mg/kg; 40 mg/kg Route of Administration: Oral; once daily; 18 days Experimental Results: The tumor growth inhibition rate (TGI) in the 20 mg/kg dose group was 57.2%. The tumor growth inhibition rate (TGI) in the 40 mg/kg dose group was 74.9%. Neither dose caused significant weight loss or histological changes in major organs (heart, liver, spleen, lungs, kidneys). |
| References |
| Molecular Formula |
C27H33CLN4
|
|---|---|
| Molecular Weight |
449.03
|
| Appearance |
Typically exists as solids at room temperature
|
| SMILES |
ClC1=CC=C([C@@H](C)NC2=NC(NCC(C)(C)C)=NC3=CC=C(C4=CCCCC4)C=C23)C=C1
|
| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2270 mL | 11.1351 mL | 22.2702 mL | |
| 5 mM | 0.4454 mL | 2.2270 mL | 4.4540 mL | |
| 10 mM | 0.2227 mL | 1.1135 mL | 2.2270 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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