Tunlametinib
Based on 1 Customer Validation
Tunlametinib is a highly selective, orally active MEK1/2 inhibitor (IC50=1.9 nM, MEK1). Tunlametinib blocks the RAS-RAF-MEK-ERK signaling pathway, arrests tumor cell cycle and promotes apoptosis. Tunlametinib potently inhibits the proliferation of RAS/RAF mutant cancer cells (such as BRAF V600E, KRAS G12C mutant cells). Tunlametinib shows synergistic anti-tumor effects with BRAF/KRASG12C/SHP2 inhibitors, Docetaxel (HY-B0011). Tunlametinib can be used to study targeted therapy for RAS/RAF mutation-driven malignancies (such as melanoma, colorectal cancer, and non-small cell lung cancer).
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- Pureza : 99.94%
- No. CAS: 1801756-06-8
- Fòrmula: C16H12F2IN3O3S
- Peso molecular:491.25
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Almacenamiento: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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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
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MEK1 |
MEK2 |
In Vitro
Tunlametinib inhibits the cell viability of BRAF/KRAS mutant cell lines: A375, Colo-829, HL-60 melanoma cells, COLO 205, HT-29 colon cancer cells, Calu-6, A549 lung cancer cells, with IC50 of 0.86 nM, 3.46 nM, 0.67 nM, 0.94 nM, 10.07 nM, 59.89 nM, respectively. Tunlametinib has no significant effect on RAS/RAF wild-type cells (H1975, MRC-5)[1].
Tunlametinib (1-9 nM; 48 h) dose-dependently increases the proportion of A375 cells in the G0/G1 phase and induces cell cycle arrest[1].
Tunlametinib (10-90 nM or 1-9 nM; 48 h) dose-dependently induces apoptosis in COLO 205 cells (10-90 nM), without significant induction effect on A375 cells (1-9 nM)[1].
Tunlametinib (0.1-100 nM; 48 h) dose-dependently reduces the level of phosphorylated ERK (p-ERK) in A375 cells with an IC50 of approximately 1.16 nM. Tunlametinib completely inhibits ERK phosphorylation at a concentration of 100 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A375 (BRAF V600E mutant melanoma)
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Concentration:1 nM, 3 nM, 9 nM
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Incubation Time:48 h
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Result:Dose-dependently increased the number of G0/G1 phase cells (from 50% to 70% of total population), indicating cell cycle arrest.
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Cell Line:A375 (BRAF V600E mutant melanoma) and COLO 205 (BRAF-mutated colon cancer cells)
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Concentration:1 nM, 3 nM, 9 nM for A375 treatment; 10 nM, 30 nM, 90 nM for COLO 205 treatment
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Incubation Time:48 h
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Result:Resulted the proportion of apoptosis cells within normal limits, suggesting no significant apoptosis-inducing effect on A375 cells.
Resulted the proportion of apoptosis of 35.1%, 38.4% and 46.6% after treated with 10, 30 and 90 nM, respectively.
In Vivo
Tunlametinib (3, 9 mg/kg; oral; once daily; 21 days) inhibits tumor growth in H1975 (BRAF/KRAS wild-type lung cancer) tumor-bearing model in female BALB/c nude mice[1].
Tunlametinib (1 mg/kg, oral; once daily; 30 days) inhibits tumor growth in BRAF-mutated colorectal cancer patient-derived xenograft (PDX) models (CR0004, CR0029, CR2179, CR6289) without causing significant changes in body weight[1].
Tunlametinib (0.25 mg/kg, 1-10 days; 0.125 mg/kg, 11-21 days; oral, once daily) combined with SHP099 (HY-100388) (I: 50 mg/kg, 1-10 days; II: 25 mg/kg, 10-21 days; oral; once every 2 days), synergistically inhibits tumor growth in the H358 (KRASG12C mutant lung cancer) tumor-bearing model[1].
Tunlametinib (1 mg/kg; oral; once daily; 21 days) combined with AMG 510 (HY-114277) (3 mg/kg; oral; once daily; 21 days), synergistically inhibits tumor growth in KRASG12C mutant tumor-bearing models[1].
Tunlametinib (1 mg/kg; oral; once daily; 10 days) combined with Vemurafenib (HY-12057) (25 mg/kg; oral; twice daily; 10 days), synergistically inhibits tumor growth in A375 (BRAF mutant melanoma) tumor-bearing models[1].
Tunlametinib (0.5 mg/kg; oral; twice daily or 3.5 mg/kg, twice weekly; for 4 weeks) combined with Docetaxel (HY-B0011) (I: 10 mg/kg in weeks 1-2, II: 7.5 mg/kg in week 3, III: 5 mg/kg in week 4; intravenous injection; once a week), synergistically inhibits tumor growth in Calu-6, H358, H441, and A549 (all RAS mutant lung cancer) tumor-bearing models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice (5-8 weeks old) with A375, HT-29, Calu-6 cell-derived xenograft (CDX) model, or CRC atient-derived xenograft (PDX)[1]
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Dosage:1, 3, 6 mg/kg for CDX model; 1 mg/kg (PO) for PDX model
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Administration:Oral administration, once daily, 21 days
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Result:Significantly inhibited tumor growth in a dose-dependent manner, with better inhibitory effect than that of AZD6244 (25 mg/kg, po, QD).
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Apoptosis Solutions
- Protocol for Cell Cycle
- Genotoxicity/Mutagenicity Study
- Cell Viability Determination by MTT Colorimetric Assay
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 1801756-06-8
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Appearance Solid
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Peso molecular 491.25
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Fòrmula C16H12F2IN3O3S
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Color Off-white to light yellow
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SMILES
O=C(C1=CC2=C(C(F)=C1NC3=CC=C(C=C3F)I)N=CS2)NOCCO
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Synonyms
HL-085
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (203.56 mM; Need ultrasonic; 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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (10.18 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (10.18 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (281 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Liu Y, et al. Preclinical characterization of tunlametinib, a novel, potent, and selective MEK inhibitor. Front Pharmacol. 2023 Sep 21;14:1271268. [Content Brief]
[2]. Sari MHM, et al. Editorial: Advances in molecular and pharmacological mechanisms of novel targeted therapies for melanoma. Front Oncol. 2024 Apr 4;14:1403778. [Content Brief]
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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0356 mL | 10.1781 mL | 20.3562 mL | 50.8906 mL |
| 5 mM | 0.4071 mL | 2.0356 mL | 4.0712 mL | 10.1781 mL | |
| 10 mM | 0.2036 mL | 1.0178 mL | 2.0356 mL | 5.0891 mL | |
| 15 mM | 0.1357 mL | 0.6785 mL | 1.3571 mL | 3.3927 mL | |
| 20 mM | 0.1018 mL | 0.5089 mL | 1.0178 mL | 2.5445 mL | |
| 25 mM | 0.0814 mL | 0.4071 mL | 0.8142 mL | 2.0356 mL | |
| 30 mM | 0.0679 mL | 0.3393 mL | 0.6785 mL | 1.6964 mL | |
| 40 mM | 0.0509 mL | 0.2545 mL | 0.5089 mL | 1.2723 mL | |
| 50 mM | 0.0407 mL | 0.2036 mL | 0.4071 mL | 1.0178 mL | |
| 60 mM | 0.0339 mL | 0.1696 mL | 0.3393 mL | 0.8482 mL | |
| 80 mM | 0.0254 mL | 0.1272 mL | 0.2545 mL | 0.6361 mL | |
| 100 mM | 0.0204 mL | 0.1018 mL | 0.2036 mL | 0.5089 mL |
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