Thymidylate Synthase Inhibitor

ICI 198583 is a thymidylate synthase (TS) inhibitor with a K_i value of 10 nM for both mouse and human TS. ICI 198583 serves as a substrate for folylpolyglutamate synthetase (FPGS) with a K_m of 40 μM. ICI 198583 exerts persistent, dose-dependent inhibition on thymidylate synthase flux in mice. ICI 198583 is applicable to relevant research on leukemia.

Idetrexed (ONX 0801) is a thymidylate synthase (TS) inhibitor with a K_i of 1.2 nM. Idetrexed can be specifically transported into α-folate receptor (α-FR)-overexpressing tumors, such as ovarian cancer.

CB 3705 is a dihydrofolate reductase (DHFR) and thymidylate synthetase (TS) inhibitor. CB 3705 inhibits L1210 cells and mutant L1210 cell line (L1210:C15) with ID₅₀s of 4.77 μM and 408 μM, respectively.

JMF4073 is a thymidylate (TMP) and cytidylate (CMP) kinases inhibitor with IC₅₀s of 0.16 μM and 0.17 μM, respectively. JMF4073 eliminates wild-type (WT)-Bcr-Abl-transformed myeloid cells in vitro and in vivo.

LC1236 is a thymidylate synthase (hTS) dimer dissociator with a target K_d of 7 μM and poor transmembrane permeability. LC1236 inhibits enzymatic activity by shifting the monomer-dimer equilibrium toward inactive monomers. LC1236 acts as a cytotoxic agent to inhibit cancer cell growth, and exerts synergistic cytotoxicity with electroporation via enhancing intracellular accumulation. LC1236 can be used in the research of cancers such as ovarian cancer and colorectal cancer.

MtTMPK-IN-2 (compound 15) is a potent Mycobacterium tuberculosis thymidylate kinase (MtTMPK) inhibitor with an IC₅₀ value of 1.1 μM. MtTMPK-IN-2 has inhibitory activity against Mtb H37Rv (MIC = 12.5 μM). MtTMPK-IN-2 exhibits certain cytotoxicity in human fibroblast cells MRC-5 (EC₅₀ = 6.1 μM). MtTMPK-IN-2 can be used for researching tuberculosis.

CB 3717 is a potent inhibitor of human thymidylate synthetase, competitively binding with 5,10-methylenetetrahydrofolate (Ki = 4.9 X 10(-9) M). It also competitively inhibits human dihydrofolate reductase with dihydrofolate (Ki = 2.3 X 10(-8) M). In WI-L2 human lymphoblastoid cells, CB 3717 treatment led to a significant decrease in cellular dTTP levels and a notable increase in dUMP levels, indicating a disruption in nucleotide metabolism. The growth-inhibitory effect of CB 3717 was reversed by thymidine supplementation, demonstrating that thymidylate synthetase became rate-limiting in the presence of this compound. Delayed thymidine supplementation beyond 8 hours resulted in severe cytotoxicity, underscoring the critical timing of nucleotide rescue strategies in CB 3717-treated cells.

MtTMPK-IN-1 (compound 3) is a potent Mycobacterium tuberculosis thymidylate kinase (MtTMPK) inhibitor with an IC₅₀ value of 2.5 μM. MtTMPK-IN-1 has moderate to weak activity against Mtb H37Rv and low cytotoxicity in human fibroblast cells MRC-5. MtTMPK-IN-1 can be used for researching tuberculosis.

Galocitabine (Ro 09-1390) is a nucleoside analog with anticancer and antiviral activity.

EGFR/HER2/TS-IN-2 (compound 17) is a potent EGFR/HER2 and TS (Thymidylate synthase) inhibitor, with IC₅₀ values of 0.173, 0.125, and 1.12 μM, respectively. EGFR/HER2/TS-IN-2 shows cytotoxic activity against MDA-MB-231 cancer cell lines, with an IC₅₀ of 1.69 µM.

Idetrexed (ONX 0801) trisodium is a thymidylate synthase (TS) inhibitor with a K_i of 1.2 nM. Idetrexed trisodium can be specifically transported into α-folate receptor (α-FR)-overexpressing tumors, such as ovarian cancer.

LC1343 is a human thymidylate synthase (hTS) inhibitor with an IC₅₀ of 7 μM. LC1343 inhibits cancer cell growth and induces apoptosis in cancer cells. LC1343 can be used for the research of ovarian cancer, colorectal cancer, and pancreatic cancer.

MtTMPK-IN-8 (compound 27) is a moderate M. tuberculosis thymidylate kinase (MtbTMPK) inhibitor. MtTMPK-IN-8 has sub-micromolar activity against mycobacteria (MICs = 0.78~9.4 μM) without significant cytotoxicity. MtTMPK-IN-8 can be used for researching tuberculosis.

TS-IN-8 is a potent thymidylate synthase (TS) inhibitor. TS-IN-8 can induce apoptosis and cause cell cycle arrest at the G2/M in MCF-7 cells. TS-IN-8 can induce nuclear morphological changes. TS-IN-8 can increase intracellular reactive oxygen species (ROS) levels. TS-IN-8 can activate intrinsic apoptosis pathways by regulating apoptosis-related proteins such as the bax/bcl-2 ratio and caspase activation. TS-IN-8 can be used for the study of breast cancer.

Vanoxonin is an inhibitor of thymidylate synthase found in Saccharopolyspora hirsuta with an IC₅₀ value of 0.7 μg/mL.

MtTMPK-IN-7 (compound 26) is a moderate M. tuberculosis thymidylate kinase (MtbTMPK) inhibitor with an IC₅₀ value of 47 μM. MtTMPK-IN-7 has sub-micromolar activity against mycobacteria (MICs = 2.3~4.7 μM) without significant cytotoxicity. MtTMPK-IN-7 can be used for researching tuberculosis.

(Rac)-Plevitrexed ((Rac)-ZD 9331; (Rac)-BGC9331)?is a racemate of Plevitrexed. Plevitrexed is an orally active and potent thymidylate synthase (TS) inhibitor. (Rac)-Plevitrexed is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Doxifluridine-d₃ is deuterated labeled Doxifluridine (HY-B0021). Doxifluridine has anticancer activity. Doxifluidine is a 5-FU prodrug. Doxifluridine is a thymidine synthase inhibitor. Doxifluridine can enhance tumor inhibition by synergizing with a variety of drugs.

Metesind glucuronate (AG 331) is an inhibitor for thymidylate synthase with K_i of 1.2 nM. Metesind glucuronate inhibits the DNA synthesis and thus inhibits the cell viability of cancer cells with IC₅₀ of 0.4-0.9 μM.

MtTMPK-IN-3 (compound 25) is a potent Mycobacterium tuberculosis thymidylate kinase (MtTMPK) inhibitor with an IC₅₀ value of 0.12 μM. MtTMPK-IN-3 has inhibitory activity against Mtb H37Rv (MIC = 12.5 μM). MtTMPK-IN-3 exhibits certain cytotoxicity in human fibroblast cells MRC-5 (EC₅₀ = 12.5 μM). MtTMPK-IN-3 can be used for researching tuberculosis.