SKLB-D18
Based on 1 Customer Validation
SKLB-D18 is an orally active ERK1/2/ERK5 inhibitor, with an IC50 of 38.69 nM and a Kd of 126.9 nM against human ERK1, an IC50 of 40.12 nM and a Kd of 209.8 nM against ERK2, and an IC50 of 59.72 nM and a Kd of 468.2 nM against ERK5. SKLB-D18 inhibits cancer cell proliferation, induces G0/G1 cell cycle arrest and apoptosis. SKLB-D18 reduces the levels of p-ERK5, p-RSKp90, p-c-Myc and c-Myc, and upregulates the level of p-ERK1/2, thereby inhibiting the ERK1/2/5 pathway in cells. SKLB-D18 increases LC3B-II accumulation, and decreases the levels of p62, p-mTOR and p-p70S6K. SKLB-D18 elevates the levels of ROS, lipid peroxidation and free ferrous ions, reduces the levels of NCOA4 and GPX4, and induces ferritin autophagy-dependent ferroptosis in cancer cells. SKLB-D18 exhibits antitumor activity in a triple-negative breast cancer xenograft mouse model. SKLB-D18 can be used in research related to triple-negative breast cancer.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 98.06%
- 分子式: C22H25ClN6O2S
- 分子量:472.99
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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ERK1 38.69 nM (IC50) |
ERK1 126.9 nM (Kd) |
ERK2 40.12 nM (IC50) |
ERK2 209.8 nM (Kd) |
ERK5 59.72 nM (IC50) |
ERK5 468.2 nM (Kd) |
SKLB-D18 (1 μM) exhibits high selectivity for ERK1, ERK2 and ERK5, with inhibition rates of 96%, 94% and 83% respectively at the concentration of 1 μM[1].
SKLB-D18 (0-20 μM; 72 h) potently inhibits the proliferation of MDA-MB-231 (IC50 0.93 μM) and MDA-MB-468 (IC50 1.05 μM) in vitro, and this activity depends on the expression of ERK1/2/5[1].
SKLB-D18 (2 μM; 2 h) directly binds to ERK1/2 and ERK5 proteins in intact MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (1-5 μM; 24 h) reduces the levels of p-ERK5, p-RSKp90, p-c-Myc and c-Myc in a dose-dependent manner, 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) potently and dose-dependently inhibits the long-term clonogenic proliferation of MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (1-5 μM; 24 h) induces dose-dependent G0/G1 cell cycle arrest in MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (0.5-2 μM; 16 h) potently and dose-dependently inhibits the migration of MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (1-5 μM; 24 h) activates complete autophagic flux in MDA-MB-231 and MDA-MB-468 cells by inhibiting the mTOR/p70S6K pathway. After 24 h of treatment, increased accumulation of LC3B-II, and decreased levels of p62, p-mTOR and p-p70S6K are observed[1].
SKLB-D18 (1-5 μM; 24 h) induces ferritinophagy-dependent ferroptosis in MDA-MB-231 and MDA-MB-468 cells by increasing the levels of ROS, lipid peroxidation and free ferrous ions, and decreasing the levels of NCOA4 and GPX4[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line: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
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Concentration:0-20 μM
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Incubation Time:72 h
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Result:Inhibited cell viability in a dose-dependent manner, with IC50 values of 0.93 μM (MDA-MB-231), 1.05 μM (MDA-MB-468), 2.31 μM (MDA-MB-436), and 3.21 μM (BT549).
Reduced anti-proliferative activity significantly in ERK1/2/5 knockdown MDA-MB-231 and MDA-MB-468 cells, with IC50 values of 14.81 μM and 19.84 μM, respectively.
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Cell Line:MDA-MB-231 and MDA-MB-468 TNBC cells
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Concentration:1-5 μM
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Incubation Time:24 h
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Result:Reduced phosphorylated ERK5 (p-ERK5), phosphorylated RSKp90 (p-RSKp90), phosphorylated c-Myc (p-c-Myc), and total c-Myc levels in both cell lines in a dose-dependent manner.
Increased phosphorylated ERK1/2 (p-ERK1/2) levels in a dose-dependent manner, while total ERK1/2 and ERK5 levels remained unchanged.
Showed superior inhibition of p-ERK5, p-RSKp90, p-c-Myc, and c-Myc at 5 μM compared to a combination of BVD-523 and XMD8-92.
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Cell Line:MDA-MB-231 and MDA-MB-468 TNBC cells
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Concentration:1-5 μM
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Incubation Time:14 days
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Result:Reduced colony formation in both cell lines in a dose-dependent manner.
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Cell Line:MDA-MB-231 and MDA-MB-468 TNBC cells
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Concentration:1-5 μM
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Incubation Time:24 h
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Result:Induced G0/G1 phase cell cycle arrest in both MDA-MB-231 and MDA-MB-468 cells in a dose-dependent manner, with significant arrest observed at all tested concentrations.
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Cell Line:MDA-MB-231 and MDA-MB-468 TNBC cells
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Concentration:0.5-2 μM
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Incubation Time:16 h
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Result:Reduced the number of migrated cells in both cell lines in a dose-dependent manner.
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Cell Line:MDA-MB-231 and MDA-MB-468 TNBC cells
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Concentration:1-5 μM (LC3/p62 immunoblotting); 5 μM (LC3 immunofluorescence, mTOR/p70S6K immunoblotting, autophagic flux assay with ±10 nM bafilomycin A1)
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Incubation Time:24 h
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Result:Increased LC3B-II accumulation and reduced p62 levels in a dose-dependent manner.
Enhanced LC3 fluorescence intensity.
Induced complete autophagic flux, as confirmed by mRFP-GFP-LC3 assay with reduced green fluorescence when co-treated with bafilomycin A1.
Reduced phosphorylated mTOR (p-mTOR) and phosphorylated p70S6K (p-p70S6K) levels.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c-nu nude mice (female, 6 weeks old, 17-19 g, subcutaneous xenograft model)[1]
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Dosage:25 mg/kg; 50 mg/kg
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Administration:p.o.; daily; 16 days
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Result:Achieved a tumor inhibition rate of 59.23% relative to the control group at 25 mg/kg.
Achieved a tumor inhibition rate of 79.88% relative to the control group at 50 mg/kg, which was superior to the combination of BVD-523 and XMD8-92 (72.66% inhibition).
Caused a dose-dependent decrease in Ki-67-positive tumor cells, with less than 20% Ki-67-positive area in the 50 mg/kg group.
Induced a dose-dependent accumulation of p-ERK1/2 in tumor tissues, while dose-dependently inhibiting p-ERK5 expression, with stronger p-ERK5 inhibition at 50 mg/kg than the BVD-523 and XMD8-92 combination group.
Showed no significant body weight loss or major organ toxicity in either treatment group.
化学情報
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性状 Solid
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分子量 472.99
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分子式 C22H25ClN6O2S
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Color Off-white to light yellow
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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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
DMSO : 35 mg/mL (74.00 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
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データシート (280 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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取扱説明書 (2659 KB)
参考文献
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.1142 mL | 10.5710 mL | 21.1421 mL | 52.8552 mL |
| 5 mM | 0.4228 mL | 2.1142 mL | 4.2284 mL | 10.5710 mL | |
| 10 mM | 0.2114 mL | 1.0571 mL | 2.1142 mL | 5.2855 mL | |
| 15 mM | 0.1409 mL | 0.7047 mL | 1.4095 mL | 3.5237 mL | |
| 20 mM | 0.1057 mL | 0.5286 mL | 1.0571 mL | 2.6428 mL | |
| 25 mM | 0.0846 mL | 0.4228 mL | 0.8457 mL | 2.1142 mL | |
| 30 mM | 0.0705 mL | 0.3524 mL | 0.7047 mL | 1.7618 mL | |
| 40 mM | 0.0529 mL | 0.2643 mL | 0.5286 mL | 1.3214 mL | |
| 50 mM | 0.0423 mL | 0.2114 mL | 0.4228 mL | 1.0571 mL | |
| 60 mM | 0.0352 mL | 0.1762 mL | 0.3524 mL | 0.8809 mL |
SKLB-D18 関連分類
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