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MTHFD1 Inhibitors

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By Targets:	Methylenetetrahydrofolate Dehydrogenase (MTHFD) (6) Apoptosis (3) DNA/RNA Synthesis (2) Parasite (1)
By Research Areas:	Cancer (6) Infection (1)

Targets Recommended: Methylenetetrahydrofolate Dehydrogenase (MTHFD) Serpin

Cat. No.	Product Name	Target	Research Areas	Chemical Structure

HY-130251

DS18561882 20+ Cited Publications	Methylenetetrahydrofolate Dehydrogenase (MTHFD)	Cancer
DS18561882 is a highly potent, isozyme-selective methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) inhibitor with an IC₅₀ value of 0.0063 μM. DS18561882 also has inhibitory effect on MTHFD1 (IC₅₀=0.57 μM). DS18561882 exhibits a good oral pharmacokinetic profile .

HY-155950

TH9619	Methylenetetrahydrofolate Dehydrogenase (MTHFD) Apoptosis	Cancer
TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both *MTHFD1* and *MTHFD2* with a IC₅₀ value of 47 nM, and selectively kills cancer cells. TH9619 induces apoptosis by blocking the S phase. TH9619 has antitumor activity .

HY-155219

TH9028	Methylenetetrahydrofolate Dehydrogenase (MTHFD) Apoptosis DNA/RNA Synthesis	Cancer
TH9028 is an inhibitor of *MTHFD1, MTHFD2* and *MTHFD2L, with IC₅₀* values of 0.5 nM, 11 nM and 27 nM, respectively. TH9028 reduces replication fork speed, induces replication stress, triggers S-phase arrest, initiates apoptosis, impairs thymidine production, and causes erroneous uracil incorporation into DNA. TH9028 can be used in research related to acute myeloid leukemia .

HY-172910

MTHFD2-IN-6	Methylenetetrahydrofolate Dehydrogenase (MTHFD)	Cancer
MTHFD2-IN-6 (compound 41) is a potent and selective *MTHFD2* inhibitor. MTHFD2-IN-6 inhibits *MTHFD1* and *MTHFD2* with IC₅₀s of 19.05 and 1.46 μM, respectively .

HY-182356

MTHFD1/2-IN-1	Methylenetetrahydrofolate Dehydrogenase (MTHFD)	Cancer
MTHFD1/2-IN-1 is an orally active dual *MTHFD1/MTHFD2* inhibitor, with IC₅₀ values of 0.26 μM and 0.031 μM against human *MTHFD1* and *MTHFD2, respectively. MTHFD1/2-IN-1 blocks one-carbon metabolism by inhibiting* the dehydrogenase activity of MTHFD1 as well as the dehydrogenase and cyclohydrolase activities of MTHFD2, thereby disrupting nucleotide biosynthesis and redox homeostasis in cancer cells. MTHFD1/2-IN-1 exhibits favorable Caco-2 permeability and hepatic microsomal metabolic stability. MTHFD1/2-IN-1 shows significant anti-leukemic activity, which not only reduces the viability of various leukemia cells but also inhibits tumor growth of acute myeloid leukemia (AML) in mouse models .

HY-148014

TH7299	Methylenetetrahydrofolate Dehydrogenase (MTHFD) Parasite Apoptosis DNA/RNA Synthesis	Infection Cancer
TH7299 is a TbFolD inhibitor with antiparasitic activity. TH7299 binds the tetrahydrofolate-binding pocket of *MTHFD2, and inhibits* *MTHFD2L* and the dehydrogenase/cyclohydrolase domain of *MTHFD1. TH7299 reduces cancer cells viability, induces apoptosis*, DNA damage. TH7299 can be used for the researches of african trypanosomiasis and acute myeloid leukemia.

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BODIPY 493/503 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Feb 1;16(1):1241. [Abstract]

MedchemExpress Validation 01

Western blot analysis of extracts from THP-1(lane 2(20μg), Jurkat (lane 3(20μg) and NIH3T3(lane 4(20μg) using FOXO1A (HY-P80132) Rabbit mAb. Proteins were transferred to a PVDF membrane and blocked with 5% non-fat milk in TBST for 2 hour at room temperature. The primary antibody (1/1000) and Loading control antibody (Beta Actin, HY-P80438, 1/10000) was used in 5% non-fat milk in TBST at 4°C overnight. Goat Anti-Mouse/Rabbit IgG-HRP Secondary Antibody (1/10000) was used for 1 hour at room temperature. Western blot analysis of extracts from THP-1(lane 2(20μg), Jurkat (lane 3(20μg) and NIH3T3(lane 4(20μg) using FOXO1A (HY-P80132) Rabbit mAb. Proteins were transferred to a PVDF membrane and blocked with 5% non-fat milk in TBST for 2 hour at room temperature. The primary antibody (1/1000) and Loading control antibody (Beta Actin, HY-P80438, 1/10000) was used in 5% non-fat milk in TBST at 4°C overnight. Goat Anti-Mouse/Rabbit IgG-HRP Secondary Antibody (1/10000) was used for 1 hour at room temperature. Western blot analysis of extracts from THP-1(lane 2(20μg), Jurkat (lane 3(20μg) and NIH3T3(lane 4(20μg) using FOXO1A (HY-P80132) Rabbit mAb. Proteins were transferred to a PVDF membrane and blocked with 5% non-fat milk in TBST for 2 hour at room temperature. The primary antibody (1/1000) and Loading control antibody (Beta Actin, HY-P80438, 1/10000) was used in 5% non-fat milk in TBST at 4°C overnight. Goat Anti-Mouse/Rabbit IgG-HRP Secondary Antibody (1/10000) was used for 1 hour at room temperature.

BODIPY 493/503 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Feb 1;16(1):1241. [Abstract]

MedchemExpress Validation 01

MedchemExpress Validation 03

Western blot analysis of extracts from THP-1(lane 2(20μg), Jurkat (lane 3(20μg) and NIH3T3(lane 4(20μg) using FOXO1A (HY-P80132) Rabbit mAb. Proteins were transferred

MedchemExpress Validation 04

MedchemExpress Validation

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MTHFD1 Inhibitors

Inhibitors & Agonists