DHFR-IN-4 is a potent dihydrofolate reductase (DHFR) inhibitor with anti-tumour activity, inhibits EGFR and HER2 and can be used to study pancreatic cancer.

EGFR/HER2/DHFR-IN-2 (Compound 4b) serves as an inhibitor for EGFR, HER2, and DHFR, with IC50 values of 0.248, 0.156, and 0.138 μM, respectively. It 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. Additionally, EGFR/HER2/DHFR-IN-2 has been shown to reduce the growth of breast cancer tumors [1].

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

EGFR/HER2/DHFR-IN-3 (compound 4c) serves as an efficacious dual inhibitor specifically targeting EGFR/HER2, exhibiting IC50 values of 0.138 μM for EGFR and 0.092 μM for HER2, respectively. Moreover, it demonstrates inhibition of DHFR with an IC50 of 0.193 μM. Notably, this compound 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), displaying an inhibition concentration half-maximum (IC50) of 4.21 μM against Mycobacterium tuberculosis DHFR enzyme and demonstrates strong antituberculosis efficacy [1].

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

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 targeting VEGFR-2 and DHFR, exhibiting IC50 values of 0.384 μM and 7.881 μM, respectively. It demonstrates effective antibacterial properties against a range of pathogens including Escherichia coli, Streptococcus faecalis, Salmonella enterica, MSSA, and MRSA, with MIC values ranging from 8 to 16 μg/mL. Additionally, this compound shows potent cytotoxic effects against various cancer cell lines such as C26, HepG2, and MCF7, with IC50 values between 2.97 and 7.12 μM, rendering it a valuable tool for cancer research [1].

DHFR-IN-2 (compound 4e) is a potent and uncompetitive inhibitor for MtDHFR with an IC 50 of 7 μM. The enzyme dihydrofolate reductase from M.tuberculosis (MtDHFR) has a high unexploited potential to be a target for new drugs against tuberculosis (TB), due to its importance for pathogen survival. DHFR-IN-2 can be used for tuberculosis (TB) research [1].

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-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-1 is a highly selective and potent anticancer compound specifically targeting MCF-7 breast cancer cells. It acts as a multi-inhibitor, targeting the EGFR/HER2 kinase and DHFR enzymes, with IC50 values of 0.153 μM, 0.108 μM, and 0.291 μM, respectively. Its mechanism of action involves cell cycle arrest at the G1/S phase and induction of apoptosis in cells [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.

HZ-1157 (DHFR-inhibitor) is a hepatitis C virus (HCV) inhibitor with inhibitory activities toward HCV NS3/4A protease.

Methotrexate (WR19039) is a folate analog, an inhibitor of the dihydrofolate reductase DHFR. Methotrexate has antimetabolic, antitumor, and immunosuppressive activities, and is commonly used in rheumatoid arthritis and various tumors.

Pemetrexed (LY-231514 Disodium Hydrate), a guanine-derived antineoplastic agent, binds to and inhibits the enzyme thymidylate synthase (TS).

PROTAC eDHFR Degrader-1 is a potent degrader targeting eDHFR-YFP and various proteins of interest (POIs), such as YFP and Luciferase [1].

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

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.

Phototrexate is a photoswitchable potent inhibitor of human dihydrofolate reductase (DHFR). Phototrexate is a photochromic analog of Methotrexate. Antifolate activity is switched on (cis-Phototrexate) by UVA (375 nm) light; it can be switched off (trans-Phototrexate) by blue or white light and by thermal relaxation in the dark.cis-Phototrexate (IC50 = 6 nM) significantly reduces the viability of HeLa cells compared withtrans-Phototrexate (IC50 = 34 μM).

Pemetrexed disodium hemipenta hydrate (LY-231514 Disodium Hydrate) is a new-type antifolate and antimetabolite for TS, DHFR, and GARFT. The Ki of Pemetrexed Disodium Hydrate for TS, DHFR and GARFT is 1.3 nM, 7.2 nM and 65 nM, respectively.

NSC309401 is an E. coli dihydrofolate reductase inhibitor with an IC50 value of 189 nM and a dissociation constant (Kd) of 14.57 nM [1].

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

Fanotaprim is a dihydrofolate reductase (DHFR) inhibitor. Fanotaprim inhibits the growth of T. gondii strains with a TgDHFR IC50 of 1.57 ± 0.11 nM and a hDHFR IC50 of 308 ± 71 nM and a hDHFR to TgDHFR selectivity ratio of 196.

Pralatrexate, (S)- is a folate analog dihydrofolate reductase (DHFR) inhibitor exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities. Pralatrexate selectively enters cells expressing RFC-1; intr

Diaveridine (AI3-23935) (DVD) is a popular antibacterial synergist that is widely used in combination with sulfonamide. It has been reported to be genotoxic to mammalian cells, but more studies are required to clarify this.

Pralatrexate (10-Propargyl-10-deazaaminopterin) is a folate analogue inhibitor of dihydrofolate reductase (DHFR) exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities.

NSC309401 is an E. coli dihydrofolate reductase inhibitor, displaying potency with an IC50 value of 189 nM and a dissociation constant (KD) of 14.57 nM [1].

Talotrexin (PT523), an analog of Aminopterin, is a nonpolyglutamatable classic antifolate that acts as a specific inhibitor of the reduced folate carrier (RFC). It selectively inhibits RFC transport, demonstrating antitumor activity by targeting dihydrofolate reductase (DHFR) to inhibit tumor growth [1] [2].

CI-898 HCl is a lipophilic antifolate inhibitor of dihydrofolate reductase (DHFR). It has enhanced binding to DHFR in the presence of the cofactor NADPH. Cl-898 HCl inhibits cell growth and halts the cell cycle at the G1/S phase in L1210 mouse lymphocytic leukemia cells and is active against methotrexate-resistant cancer cell lines. It also enhances the activity of doxorubicin, cyclophosphamide, and 6-thioguanine (6-TG) in mice with advanced stage P338 leukemia.

CH-1504, dihydrofolate reductase (DHFR) inhibitor, is used potentially for the treatment of rheumatoid arthritis.

Pyrimethamine (Pirimecidan) is a competitive inhibitor of dihydrofolate reductase (DHFR), used as an antimalarial drug.

EGFR/HER2-IN-6 (compound 43) is a dual EGFR/HER2 and DHFR inhibitor with potent activity against EGFR kinase, HER2 kinase, and DHFR, characterized by IC50 values of 0.122 μM, 0.078 μM, and 0.585 μM, respectively. This compound displays notable anticancer properties in various cancer cell lines, while demonstrating a favorable safety profile and selectivity indices. Consequently, EGFR/HER2-IN-6 holds promise as a valuable tool in cancer research [1].

Pralatrexate, (R)- is a folate analog dihydrofolate reductase (DHFR) inhibitor exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities. Pralatrexate selectively enters cells expressing RFC-1; intr

Antibacterial agent 26 is an antimicrobial compound that is a potent DHFR inhibitor (S. aureus DHFR Ki of 0.020 nM).

Aditoprime (Aditoprim) is a selective inhibitor of bacterial dihydrofolate reductase (DHFR) that inhibits the transformation of dihydrofolic acid to tetrahydrofolic acid. Aditoprime shows good antibacterial activity and broad antimicrobial spectrum, and moreover, excellent pharmacokinetics. Aditoprime inhibits L.casei and E.coli DHFR with IC 50 of 520 and 47 nM, respectively [1] [2] [3].

11-Oxahomoaminopterin exhibits antifolate activity against two folate-requiring microorganisms and inhibited Lactobacillus casei DHFR.

EGFR/HER2-IN-8 (compound 34) is an inhibitor of EGFR/HER2 and DHFR with IC50 values of 0.45, 0.244 and 5.669 μM for EGFR, HER2 and DHFR, respectively. EGFR/HER2-IN-8 can be used in the cancer research that exhibits anticancer activity against several cancer cell lines with high safety profile and selectivity indices [1].

Tetroxoprim is an antimicrobial DHFR inhibitor.

DQn-1, a potent antifolate, demonstrates efficacy against Mycobacterium tuberculosis (Mtb) with an MIC 90 of 0.03 µM. It inhibits the DHFR enzyme, exhibiting IC 50 values of 8.7 nM for Mtb DHFR and 7.6 nM for the human counterpart [1].

EGFR/HER2-IN-7 is a highly selective and potent anticancer compound specifically designed to target MCF-7 breast cancer cells. It functions as a dual inhibitor, targeting both EGFR/HER2 kinases and DHFR (dihydrofolate reductase). Its inhibitory activities are measured with IC50 values of 0.18 μM for EGFR, 0.146 μM for HER2, and 0.907 μM for DHFR [1].

Brivudine monophosphate is a phosphate ester of Brivudine. Brivudine, also known as bromovinyl-deoxyuridine, is a uridine derivative and nucleoside analog with pro-apoptotic and chemosensitizing properties. In vitro, bromovinyl-deoxyuridine (BVDU) has been shown to downregulate the multifunctional DNA repair enzyme APEX nuclease 1, resulting in the inhibition of DNA repair and the induction of apoptosis. In addition, this agent may inhibit the expression of STAT3 (signal transducer and activator of transcription 3), which may result in the downregulation of vascular endothelial growth factor (VEGF). BVDU has also been found to inhibit the upregulation of chemoresistance genes (Mdr1 and DHFR) during chemotherapy.

WR99210 is a potent, orally available and less toxic dihydrofolate reductase (DHFR) inhibitor (IC50<0.075 nM). WR99210 has good antiparasitic activity against P. vivax and P. falciparum strains (including P. falciparum strains resistant to Pyrimethamine ) and T. gondii.

Antileishmanial agent-17, a coumarin hybrid, exhibits potent antileishmanial activity (IC50 <0.78 μM) while proving non-toxic to normal VERO cells. It specifically interacts with the folate pathway enzymes pteridine reductase and DHFR-TS. Efficacy against the promastigote form is highlighted by an IC50 value of 0.40 μM, and against the amastigote form, an IC50 of 0.68 μM, respectively.

Brodimoprim is an inhibitor of dihydrofolate reductase(DHFR). Brodimoprim is also a long-acting broad-spectrum antibacterial agent characterized by a good pharmacokinetic profile.

OYYF-175 is an antimicrobial antifolate. OYYF-175 exhibits potent broad-spectrum antibacterial activities, especially against multi-drug resistant Gram-Negative-strains. OYYF-175 is an inhibitor of dihydrofolate reductase (DHFR) with an IC 50 of 2.36 nM for Escherichia coli DHFR.

Piritrexim isethionate is a lipid-soluble inhibitor of dihydrofolate reductase (DHFR) that appears to be an active agent in patients with metastatic urothelial cancer when administered as a 5-day, low-dose oral schedule.

Pemetrexed disodium (LY-231514) is a parenterally administered folate antagonist and antineoplastic agent, used in the treatment of non-small cell lung cancer and malignant mesothelioma. Pemetrexed disodium therapy has been associated with moderate rates of serum enzyme elevations during therapy, but has not been convincingly linked to instances of acute, clinically apparent liver injury.