Cat. No.: HY-174981

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, FGFR3^Y373C mutant cancers, and FGFR3-TACC3 fusion-positive cancers.
(Pink: FGFR3 ligand (HY-160013); Blue: VHL ligand (HY-125905); Black: linker).

연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.

Purity: 98.05%
화학식: C₅₅H₆₈Cl₂FN₁₁O₈S
분자량:1133.17

보관:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

LC-MF-4 Chemical Structure

Amount: USD 0.00

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- 제품 설명
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
용액&용해도
- In Vitro
- In Vivo
순도&문서
References
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

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, FGFR3^Y373C mutant cancers, and FGFR3-TACC3 fusion-positive cancers^[1]. (Pink: FGFR3 ligand (HY-160013); Blue: VHL ligand (HY-125905); Black: linker).

IC₅₀ & Target^[1]

FGFR3

16.6 nM (IC₅₀)

All PROTACs Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
RT-112	IC₅₀	28.98 nM	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.	40575843
KMS-11	DC₅₀	30.8 nM	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.	40575843
KMS-11	IC₅₀	25.6 nM	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.	40575843
BaF3	IC₅₀	7.03 nM	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.	40575843

In Vitro

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 FGFR3^Y373C 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 FGFR3^Y373C-mutant KMS-11 cells^[1].
LC-MF-4 (0.1-10 μM; 72 h) potently inhibits the proliferation of KMS-11 cells carrying the FGFR3^Y373C 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.

Cell Proliferation Assay^[1]

Cell Line:

RT112
Concentration:

0.01, 0.1, 1, 10,100 nM; 1, 10 μM
Incubation Time:

72 h
Result:

Inhibited RT112 cell viability in a concentration-dependent manner.
Achieved an IC₅₀ value of 28.98 nM.

Western Blot Analysis^[1]

Cell Line:

human myeloma KMS-11 cells (FGFR3 Y373C mutant)
Concentration:

0.5, 1.5, 4.3, 13, 41, 123, 370, 1111, 10000 nM (dose-dependent degradation assay); 100 nM (time-course assay)
Incubation Time:

8 h (dose-dependent degradation assay); 6 h, 8 h, 12 h (time-course assay)
Result:

Induced dose-dependent FGFR3 degradation with a DC₅₀ of 30.8 nM and a D_max 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.

Western Blot Analysis^[1]

Cell Line:

human myeloma KMS-11 cells (FGFR3 Y373C mutant)
Concentration:

20, 100, 500, 1000 nM
Incubation Time:

8 h
Result:

Completely blocked FGF2-stimulated FGFR phosphorylation at 100 nM.
Significantly reduced phosphorylation of downstream signaling proteins FRS2α, PLCγ, and AKT compared to control.

Cell Proliferation Assay^[1]

Cell Line:

human myeloma KMS-11 cells (FGFR3 Y373C mutant); NCI-H1975 cells; MV-4-11 cells; HEK293 cells
Concentration:

0.1, 1, 10, 100 nM; 1, 10, 10 μM
Incubation Time:

72 h
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.

Western Blot Analysis^[1]

Cell Line:

engineered Ba/F3-FGFR3-TACC3 cells
Concentration:

1, 4, 12, 37, 111, 333, 1000 nM
Incubation Time:

8 h
Result:

Induced dose-dependent reduction of FGFR3-TACC3 fusion protein levels.
Decreased FGFR phosphorylation.

Cell Proliferation Assay^[1]

Cell Line:

engineered Ba/F3-FGFR3-TACC3 cells
Concentration:

1, 10, 100, 1000 nM
Incubation Time:

72 h
Result:

Potently inhibited Ba/F3-FGFR3-TACC3 cell proliferation with an IC₅₀ of 7.03 nM.

Parmacokinetics

Species	Dose	Route	F	T_1/2	T_max	C_max	AUC_0-∞
Mice^[1]	20 mg/kg	p.o.	4.4 %	4 h	1.664 h	786.3 ng/mL	949.8 ng/mL·h
Mice^[1]	5 mg/kg	i.v.	/	1.784 h	0.083 h	2405.3 ng/mL	5432 ng/mL·h

In Vivo

LC-MF-4 (20 mg/kg; p.o.; once daily for 14 days) achieves 50.2% tumor growth inhibition in FGFR3-TACC3 xenograft mice, with significant reduction of target protein and downstream signaling, and no observed toxicity^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

BALB/c nude mice (female, 6 weeks old)^[1]
Dosage:

20 mg/kg
Administration:

p.o.; once daily for 14 days
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

Appearance Solid
분자량 1133.17
화학식 C₅₅H₆₈Cl₂FN₁₁O₈S
Color White to off-white
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
선적

Room temperature in continental US; may vary elsewhere.

보관

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

용액&용해도

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

0.8825 mL

4.4124 mL

8.8248 mL

5 mM

0.1765 mL

0.8825 mL

1.7650 mL

10 mM

0.0882 mL

0.4412 mL

0.8825 mL

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.

몰농도 계산기

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

농도 희석 계산기

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (2.21 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

순도&문서

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Zheng L, et al. LC-MF-4, a Novel FGFR3 Degrader for Therapeutic Intervention in FGFR3-Altered Cancers. Journal of medicinal chemistry. 2025 Jul 10;68(13):13858-13871. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

Bioz

Keywords

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수량:
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수량:

LC-MF-4

All PROTACs Isoforms

Biological Activity

Chemical Information

용액&용해도

순도&문서

References

Help & FAQs

Complete Stock Solution Preparation Table

LC-MF-4 Related Classifications

HY-174981 Related Classifications

Bioz