LC-MF-4
LC-MF-4 is an orally active VHL-recruiting FGFR3 PROTAC degrader and hERG potassium channel inhibitor. LC-MF-4 has an IC50 of 16.6 nM against human FGFR3, exhibits inhibitory activity against hERG potassium channels, suppresses the expression of genes related to mitochondrial biogenesis and ATP synthesis, inhibits cancer cell proliferation, and shows significant antitumor activity in mice. LC-MF-4 can be used in the research of bladder cancer, urothelial carcinoma, FGFR3Y373C mutant cancers, and FGFR3-TACC3 fusion-positive cancers.
(Pink: FGFR3 ligand (HY-160013); Blue: VHL ligand (HY-125905); Black: linker).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté: 98.05%
- Formule: C55H68Cl2FN11O8S
- Masse moléculaire:1133.17
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Stockage: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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
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FGFR3 16.6 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| RT-112 | IC50 |
28.98 nM
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Antiproliferative activity against human RT112 cells assessed as reduction in cell viability incubated for 72 hrs by cell proliferation viability assay.
Antiproliferative activity against human RT112 cells assessed as reduction in cell viability incubated for 72 hrs by cell proliferation viability assay.
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40575843 |
| KMS-11 | DC50 |
30.8 nM
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Dose-dependent FGFR3 degradation in human myeloma KMS-11 cells (FGFR3 Y373C mutant) measured via Western blotting or immunofluorescence after 8 h treatment.
Dose-dependent FGFR3 degradation in human myeloma KMS-11 cells (FGFR3 Y373C mutant) measured via Western blotting or immunofluorescence after 8 h treatment.
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40575843 |
| KMS-11 | IC50 |
25.6 nM
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Antiproliferative activity against human myeloma KMS-11 cells (FGFR3 Y373C mutant) assessed as reduction in cell viability incubated for 72 hrs.
Antiproliferative activity against human myeloma KMS-11 cells (FGFR3 Y373C mutant) assessed as reduction in cell viability incubated for 72 hrs.
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40575843 |
| BaF3 | IC50 |
7.03 nM
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Antiproliferative activity against engineered Ba/F3-FGFR3-TACC3 cells assessed as reduction in cell viability incubated for 72 hrs.
Antiproliferative activity against engineered Ba/F3-FGFR3-TACC3 cells assessed as reduction in cell viability incubated for 72 hrs.
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40575843 |
LC-MF-4 (0.01 nM-10 μM; 72 h) inhibits the proliferation of RT112 cells, with an IC50 value of 28.98 nM[1].
LC-MF-4 (0.1 nM-1 μM; 6-12 h) potently inhibits the activity of the purified FGFR3 kinase domain, with an IC50 of 16.6 nM[1].
LC-MF-4 (0.5 nM-10 μM; 6-12 h) potently and persistently degrades FGFR3 in KMS-11 cells harboring the FGFR3Y373C mutation, with a DC50 of 30.8 nM[1].
LC-MF-4 (500 nM; 8 h) exhibits excellent proteome selectivity for FGFR3 degradation in KMS-11 cells[1].
LC-MF-4 (20-1000 nM; 8 h) potently inhibits the activation of FGFR3 and its downstream signaling pathways in FGFR3Y373C-mutant KMS-11 cells[1].
LC-MF-4 (0.1-10 μM; 72 h) potently inhibits the proliferation of KMS-11 cells carrying the FGFR3Y373C mutation, with an IC50 of 25.6 nM, whereas it exerts no significant effects on non-FGFR3-driven cancer cells and normal cells[1].
LC-MF-4 (1-1000 nM; 8 h) degrades the FGFR3-TACC3 fusion protein and inhibits its kinase activity in engineered Ba/F3-FGFR3-TACC3 cells[1].
LC-MF-4 (1-100 nM; 72 h) potently inhibits the proliferation of Ba/F3 cells driven by the FGFR3-TACC3 fusion gene, with an IC50 of 7.03 nM[1].
LC-MF-4 (100 nM) potently inhibits colony formation of FGFR3-TACC3 fusion-positive RT112 bladder cancer cells[1].
LC-MF-4 (100 nM; 8 h) inhibits mitochondrial metabolism and biogenesis in FGFR3-TACC3 fusion-positive RT112 bladder cancer cells by downregulating the expression of key genes, ATP production, and PGC1α levels[1].
LC-MF-4 (100 nM; 6 h) potently degrades FGFR1 in NCI-H1581 cells and FGFR2 in KATO III cells[1].
LC-MF-4 (0.1-30 μM) exhibits extremely weak inhibitory activity against hERG potassium channels, with an inhibition rate of less than 25% at 30 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RT112
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Concentration:0.01, 0.1, 1, 10,100 nM; 1, 10 μM
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Incubation Time:72 h
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Result:Inhibited RT112 cell viability in a concentration-dependent manner.
Achieved an IC50 value of 28.98 nM.
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Cell Line:human myeloma KMS-11 cells (FGFR3 Y373C mutant)
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Concentration:0.5, 1.5, 4.3, 13, 41, 123, 370, 1111, 10000 nM (dose-dependent degradation assay); 100 nM (time-course assay)
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Incubation Time:8 h (dose-dependent degradation assay); 6 h, 8 h, 12 h (time-course assay)
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Result:Induced dose-dependent FGFR3 degradation with a DC50 of 30.8 nM and a Dmax of 85% after 8 h treatment.
Reduced FGFR3 levels to 15% of control after 8 h treatment with 100 nM, and levels remained below 50% for 16 h post-washout.
Confirmed marked reduction of FGFR3 signal after 6 or 12 h treatment with 100 nM.
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Cell Line:human myeloma KMS-11 cells (FGFR3 Y373C mutant)
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Concentration:20, 100, 500, 1000 nM
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Incubation Time:8 h
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Result:Completely blocked FGF2-stimulated FGFR phosphorylation at 100 nM.
Significantly reduced phosphorylation of downstream signaling proteins FRS2α, PLCγ, and AKT compared to control.
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Cell Line:human myeloma KMS-11 cells (FGFR3 Y373C mutant); NCI-H1975 cells; MV-4-11 cells; HEK293 cells
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Concentration:0.1, 1, 10, 100 nM; 1, 10, 10 μM
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Incubation Time:72 h
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Result:Inhibited KMS-11 cell proliferation efficiently with an IC50 of 25.6 nM.
Showed no significant antiproliferative activity against NCI-H1975, MV-4-11, or HEK293 cells.
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Cell Line:engineered Ba/F3-FGFR3-TACC3 cells
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Concentration:1, 4, 12, 37, 111, 333, 1000 nM
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Incubation Time:8 h
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Result:Induced dose-dependent reduction of FGFR3-TACC3 fusion protein levels.
Decreased FGFR phosphorylation.
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Cell Line:engineered Ba/F3-FGFR3-TACC3 cells
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Concentration:1, 10, 100, 1000 nM
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Incubation Time:72 h
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Result:Potently inhibited Ba/F3-FGFR3-TACC3 cell proliferation with an IC50 of 7.03 nM.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (female, 6 weeks old)[1]
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Dosage:20 mg/kg
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Administration:p.o.; once daily for 14 days
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Result:Achieved 50.2% tumor growth inhibition.
Significantly reduced final tumor weight compared to vehicle control.
Significantly reduced FGFR3-TACC3 protein levels in tumor lysates.
Showed superior inhibition of downstream protein phosphorylation (PLCγ, AKT, ERK1/2) compared to LC-CS-4.
Caused no significant body weight loss or adverse effects during treatment.
Chemical Information
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Appearance Solid
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Masse moléculaire 1133.17
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Formule C55H68Cl2FN11O8S
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Color White to off-white
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SMILES
COC1=CC(OC)=C(C(NC(N(C2=NC=NC(NC3=CC=C(C=C3)N4CCN(CC4)CCCCCOC5=CC(C6=C(N=CS6)C)=CC=C5CNC([C@@H]7C[C@H](CN7C([C@H](C(C)(C)C)NC(C8(CC8)F)=O)=O)O)=O)=C2)C)=O)=C1Cl)Cl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
DMSO : 100 mg/mL (88.25 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)
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: ≥ 2.5 mg/mL (2.21 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
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.
Pureté et documentation
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Fiche technique (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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Instruction de manipulation (2659 KB)
Références
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 | 0.8825 mL | 4.4124 mL | 8.8248 mL | 22.0620 mL |
| 5 mM | 0.1765 mL | 0.8825 mL | 1.7650 mL | 4.4124 mL | |
| 10 mM | 0.0882 mL | 0.4412 mL | 0.8825 mL | 2.2062 mL | |
| 15 mM | 0.0588 mL | 0.2942 mL | 0.5883 mL | 1.4708 mL | |
| 20 mM | 0.0441 mL | 0.2206 mL | 0.4412 mL | 1.1031 mL | |
| 25 mM | 0.0353 mL | 0.1765 mL | 0.3530 mL | 0.8825 mL | |
| 30 mM | 0.0294 mL | 0.1471 mL | 0.2942 mL | 0.7354 mL | |
| 40 mM | 0.0221 mL | 0.1103 mL | 0.2206 mL | 0.5516 mL | |
| 50 mM | 0.0176 mL | 0.0882 mL | 0.1765 mL | 0.4412 mL | |
| 60 mM | 0.0147 mL | 0.0735 mL | 0.1471 mL | 0.3677 mL | |
| 80 mM | 0.0110 mL | 0.0552 mL | 0.1103 mL | 0.2758 mL |
LC-MF-4 Related Classifications
HY-174981 Related Classifications
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