dhfr

DHFR-IN-4 is a potent dihydrofolate reductase (DHFR) inhibitor with anti-tumor activity, which also inhibits EGFR and HER2, and is useful for studying pancreatic cancer.

P 218 is a novel DHFR inhibitor with antimalarial activity and antifolate effects and can be used to study Buruli ulcer.

Sulfameter (Sulfametoxydiazine) is a long-acting sulfonamide antibacterial agent used to treat urinary tract infections and leprosy.

Trimethoprim (NSC-106568) is a Dihydrofolate Reductase Inhibitor Antibacterial. The mechanism of action of trimethoprim is as a Dihydrofolate Reductase Inhibitor, and Cytochrome P450 2C8 Inhibitor, and Organic Cation Transporter 2 Inhibitor.

Gentamicin sulfate (SCH9724) is a wide-spectrum, aminoglycoside antibiotic used to inhibit protein synthesis in sensitive organisms.

4′-DTMP (4-Demethyltrimethoprim) is a potent DHFR inhibitor with antimicrobial activity that induces additional local interactions with the enzyme and inhibits Escherichia coli.

Talotrexin ammonium is a non-polyglutamic acid antifolate. Talotrexin ammonium inhibits tumor growth by targeting dihydrofolate reductase (DHFR), thereby improving anti-tumor activity in a wide range of cancer models, helping to inhibit tumor growth.

DHFR-IN-3 (7-bromoquinazoline-2,4-diamine) is a dihydrofolate reductase (DHFR) inhibitor.

DHFR-IN-2 (compound 4e) is a potent and uncompetitive inhibitor of MtDHFR, with an IC50 of 7 μM. The enzyme dihydrofolate reductase from M. tuberculosis (MtDHFR) holds high unexploited potential as a drug target due to its importance for pathogen survival. DHFR-IN-2 can be used for tuberculosis (TB) research [1].

VEGFR-2 DHFR-IN-2 (compound 5b) is a dual inhibitor targeting VEGFR-2 and DHFR, with respective IC50 values of 0.623 μM and 9.085 μM. It demonstrates potent cytotoxicity against C26, HepG2, and MCF7 cancer cell lines, with IC50 values ranging from 3.59 μM to 8.38 μM. VEGFR-2 DHFR-IN-2 holds promise for cancer research [1].

VEGFR-2 DHFR-IN-1 (compound 8b) is a chemical inhibitor of VEGFR-2 and DHFR, with IC50 values of 0.384 μM and 7.881 μM, respectively. It possesses effective antibacterial activity against pathogens including Escherichia coli, Streptococcus faecalis, Salmonella enterica, MSSA, and MRSA, with MIC values ranging from 8 to 16 μg mL. Additionally, it exhibits potent cytotoxicity against cancer cell lines C26, HepG2, and MCF7, with IC50 values between 2.97 and 7.12 μM, making it a valuable tool for cancer research [1].

DHFR-IN-22 (Compound 8) is a DHFR (Dihydrofolate Reductase) inhibitor that falls under the category of 2,4-diaminopyrimidine compounds. It demonstrates significant inhibitory activity against isolated DHFR enzyme and major nontuberculous mycobacteria (NTM) species, specifically Mycobacterium avium and Mycobacterium abscessus. The compound has an IC50 of 1.1 nM and a MIC of 1.5 μg mL for M. abscessus, and an IC50 of 6.3 nM and a MIC of 0.1 μg mL for M. avium, while its IC50 for human DHFR is 2100 nM. DHFR-IN-22 may be promising for developing new strategies to combat NTM infections.

DHFR-IN-9 (compound 8A), a dihydrofolate reductase (DHFR) inhibitor, impedes purine and thymidylate biosynthesis, pivotal in cell proliferation and growth. It demonstrates potency against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 with an IC50 of 0.25 μg mL and exhibits anti-infective properties in mouse systemic and thigh infection models at doses of 2.5 mg kg and 5 mg kg administered intraperitoneally (ip). Furthermore, DHFR-IN-9 shows greater anticancer efficacy in a mouse breast cancer model compared to paclitaxel (Y-B0015), at a regimented dosage of 2.5 mg kg ip every three days [1].

DHFR-IN-1 is a selective and potent inhibitor of DHFR (dihydrofolate reductase) (IC50: 40.71 nM). DHFR-IN-1 exhibited some antifungal activity and good antibacterial activity against Gram-positive and Gram-negative bacteria.DHFR-IN-1 showed good synergy with Levofloxacin with FIC (partial inhibitory concentration index) = 0.249.

DHFR-IN-20 (Compound LA1) is an inhibitor of dihydrofolate reductase (DHFR) targeting the malignant strains of the malaria parasite. It exhibits inhibition constants (Kis) of 0.16 nM, 0.30 nM, and 6.6 nM for PfDHFR-WT, PfDHFR-QM, and HsDHFR, respectively. Additionally, DHFR-IN-20 demonstrates antimalarial activity, with IC50 values of 1.4 nM against parasites carrying the wild-type (TM4 8.2) PfDHFR enzyme and 1.6 μM against those with the quadruple mutation (V1 S)PfDHFR.

DNA Gyrase DHFR-IN-1 is a dual inhibitor targeting bacterial DNA gyrase and DHFR, with IC50 values of 182 μM and 3.90 μM against E. coli DNA gyrase and DHFR, respectively. This compound exhibits both bactericidal and antifungal activities.

DHFR-IN-8 (compound 6r), a dihydrofolate reductase (DHFR) inhibitor, disrupts purine and thymidylate biosynthesis critical for cell proliferation and growth. This compound effectively suppresses methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 with an IC50 of 15.6 ng mL in mouse models of systemic and thigh infections [1].

EGFR HER2 DHFR-IN-2 (Compound 4b) is an inhibitor of EGFR, HER2, and DHFR, with IC50 values of 0.248, 0.156, and 0.138 μM, respectively, and exhibits anticancer activity, displaying IC50 values of 9.14, 7.33, 14.18, 24.87, 20.07, and 6.16 μM in Hep G2, HeLa, HEp-2, HCT 116, PC-3, and MCF7 cancer cell lines, respectively; it also reduces the growth of breast cancer tumors [1].

DHFR-IN-21 (compound 5p) is an inhibitor of dihydrofolate reductase.

DHFR-IN-19 (Compound 2g) is a selective inhibitor of TbDHFR with a Ki of 9 nM. It exhibits antitrypanosomal activity, inhibiting Trypanosoma brucei with an EC50 of 14.5 μM.

DHFR-IN-11 (compound 6b) is a DHFR inhibitor with an IC50 value of 5.70 μM, demonstrating efficacy against the M. tuberculosis DHFR enzyme [1].

EGFR HER2 DHFR-IN-3 (compound 4c) is an efficacious dual inhibitor of EGFR HER2 with IC50 values of 0.138 μM for EGFR and 0.092 μM for HER2, respectively, and also inhibits DHFR with an IC50 of 0.193 μM. It induces cell cycle arrest in the S phase and triggers apoptosis in MCF7 breast cancer cells [1].

DHFR-IN-10 (compound 4c) is a potent inhibitor of dihydrofolate reductase (DHFR), exhibiting an IC50 of 4.21 μM against Mycobacterium tuberculosis DHFR enzyme and demonstrating strong antituberculosis efficacy [1].

DHFR-IN-5, an orally active and potent inhibitor of dihydrofolate reductase (DHFR), exhibits a K_i value of 0.54 nM against the quadruple mutant Plasmodium falciparum DHFR, demonstrating anti-malarial activity.