| Size | Price | Stock | Qty |
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| Other Sizes |
| ln Vitro |
SKLB-D18 (1 μM) exhibits high selectivity for ERK1, ERK2, and ERK5, with inhibition rates of 96%, 94%, and 83%, respectively, at a concentration of 1 μM [1]. SKLB-D18 (0–20 μM; 72 h) effectively inhibits the proliferation of MDA-MB-231 (IC50 0.93 μM) and MDA-MB-468 (IC50 1.05 μM) cells in vitro, and this activity is dependent on the expression of ERK1/2/5 [1]. SKLB-D18 (2 μM; 2 h) can directly bind to ERK1/2 and ERK5 proteins in intact MDA-MB-231 and MDA-MB-468 cells [1]. SKLB-D18 (1-5 μM; 24 h) dose-dependently reduced the levels of p-ERK5, p-RSKp90, pc-Myc, and c-Myc, while upregulating the level of p-ERK1/2, thereby inhibiting the ERK1/2/5 pathway in MDA-MB-231 and MDA-MB-468 cells [1]. SKLB-D18 (1-5 μM; 14 days) dose-dependently and potently inhibited the long-term colony formation and proliferation of MDA-MB-231 and MDA-MB-468 cells [1]. SKLB-D18 (1-5 μM; 24 h) dose-dependently induced G0/G1 phase cell cycle arrest in MDA-MB-231 and MDA-MB-468 cells [1]. SKLB-D18 (0.5–2 μM; 16 h) effectively and in a dose-dependent manner inhibited the migration of MDA-MB-231 and MDA-MB-468 cells[1]. SKLB-D18 (1–5 μM; 24 h) activated complete autophagy in MDA-MB-231 and MDA-MB-468 cells by inhibiting the mTOR/p70S6K pathway. After 24 hours of treatment, increased LC3B-II accumulation was observed, while p62, p-mTOR, and p-p70S6K levels decreased[1]. SKLB-D18 (1–5 μM; 24 h) induced ferritin autophagy-dependent ferroptosis in MDA-MB-231 and MDA-MB-468 cells by increasing ROS, lipid peroxidation, and free ferrous ions, and decreasing NCOA4 and GPX4 levels[1].
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| ln Vivo |
SKLB-D18 (25-50 mg/kg; orally; once daily for 16 days) inhibited the growth of triple-negative breast cancer tumors in a dose-dependent manner in a subcutaneous xenograft mouse model [1].
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| Cell Assay |
Cell viability assay [1]
Cell Types: Triple-negative breast cancer (TNBC) cell lines MDA-MB-231, MDA-MB-468, MDA-MB-436, BT549; ERK1/2/5 knockdown MDA-MB-231 and MDA-MB-468 cells Tested Concentrations: 0-20 μM Incubation Duration: 72 hours Experimental Results: Cell viability was inhibited in a dose-dependent manner, and the IC50 values were 0.93 μM (MDA-MB-231), 1.05 μM (MDA-MB-468), 2.31 μM (MDA-MB-436) and 3.21 μM (BT549), respectively. In ERK1/2/5 knockdown MDA-MB-231 and MDA-MB-468 cells, antiproliferative activity was significantly reduced, with IC50 values of 14.81 μM and 19.84 μM, respectively. Western Blot Analysis [1] Cell Types: MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) cells Tested Concentrations: 1-5 μM Incubation Duration: 24 hours Experimental Results: Phosphorylated ERK5 (p-ERK5), phosphorylated RSKp90 (p-RSKp90), phosphorylated c-Myc (pc-Myc), and total c-Myc levels decreased in a dose-dependent manner in both cell lines. Phosphorylated ERK1/2 (p-ERK1/2) levels increased in a dose-dependent manner, while total ERK1/2 and ERK5 levels remained unchanged. Compared with the combination of BVD-523 and XMD8-92, it showed stronger inhibitory effects on p-ERK5, p-RSKp90, pc-Myc and c-Myc at 5 μM. |
| Animal Protocol |
Animal/Disease Models:BALB/c-nu nude mice (female, 6 weeks old, 17-19 g, subcutaneous xenograft model)[1]
Doses: 25 mg/kg; 50 mg/kg Route of Administration: Oral; once daily; 16 days Experimental Results: The tumor inhibition rate in the 25 mg/kg dose group was 59.23% (relative to the control group). The tumor inhibition rate in the 50 mg/kg dose group was 79.88% (relative to the control group), which was superior to the combined use of BVD-523 and XMD8-92 (inhibition rate of 72.66%). The drug dose-dependently reduced the number of Ki-67 positive tumor cells, and the proportion of Ki-67 positive areas in the 50 mg/kg group was less than 20%. This drug dose-dependently induces the accumulation of p-ERK1/2 in tumor tissue and dose-dependently inhibits the expression of p-ERK5. The 50 mg/kg group showed stronger inhibitory effects on p-ERK5 than the combined BVD-523 and XMD8-92 group. No significant weight loss or major organ toxicity was observed in either treatment group. |
| References |
| Molecular Formula |
C22H25CLN6O2S
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|---|---|
| Molecular Weight |
472.99
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| Appearance |
Off-white to light yellow solid
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| SMILES |
CN(C)CC1=CC=CC(NC2=NC(C3=CSC(C(NN4CCOCC4)=O)=C3)=C(Cl)C=N2)=C1
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| 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)
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| Solubility (In Vitro) |
DMSO : ~35 mg/mL (~74.00 mM; ultrasonic and warming and heat to 60°C)
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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 | 2.1142 mL | 10.5710 mL | 21.1421 mL | |
| 5 mM | 0.4228 mL | 2.1142 mL | 4.2284 mL | |
| 10 mM | 0.2114 mL | 1.0571 mL | 2.1142 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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