SHMT

SHIN1 (RZ-2994) is a human serine hydroxymethyltransferse 1 and 2 (SHMT1/2) inhibitor with IC50s of 5 and 13 nM, respectively, in an in vitro assay.

Lometrexol, a potent GARFT inhibitor, effectively blocks glycinamide ribonucleotide formyltransferase activity, thereby disrupting de novo purine synthesis. This inhibition leads to abnormal cell proliferation, apoptosis, and potential cell cycle arrest, demonstrating its anticancer properties. Additionally, Lometrexol acts as an inhibitor of human serine hydroxymethyltransferase 1 and 2 (hSHMT1/2), further influencing metabolic processes in cancer research applications.

TD034 is a selective, reversible, and noncovalent inhibitor of HDAC11, exhibiting an IC50 value of 5.1 nM and a Ki of 1.5 nM. This compound specifically targets HDAC11 without affecting other histone deacetylases or sirtuins, and it inhibits the defatty acylation of the substrate SHMT2. Additionally, TD034 reduces the levels of YAP1 through its action on HDAC11. This reagent is suitable for investigating the role of HDAC11 in lung cancer research.

AGF347 is a potent multi-targeted antifolate that primarily inhibits serine hydroxymethyltransferase (SHMT)2 in mitochondria and SHMT1 in the cytosol, thereby disrupting de novo purine biosynthesis. This compound induces apoptosis, inhibits mTOR signaling, reduces glutathione (GSH) levels, and increases reactive oxygen species (ROS). AGF347 effectively inhibits the proliferation of both Cisplatin-sensitive and resistant epithelial ovarian cancer (EOC) cells and demonstrates significant antitumor efficacy in SKOV3 EOC xenograft mouse models, making it a valuable tool for ovarian cancer research.

(Rac)-SHIN2 is a pyrazolopyran derivative that functions as a selective inhibitor of serine hydroxymethyltransferase (SHMT). This compound demonstrates significant antibacterial activity, effectively targeting both vancomycin-susceptible and vanA-type vancomycin-resistant Enterococcus, while exhibiting low cytotoxicity towards Hep2 cells. The potential applications of (Rac)-SHIN2 include investigation into bacterial resistance mechanisms and the development of novel antibacterial therapeutics.

(+)SHIN2 is a selective inhibitor of serine hydroxymethyltransferase (SHMT), a key enzyme involved in folate metabolism and one-carbon metabolism. This compound has been shown to enhance survival in mouse models of NOTCH1-driven acute lymphoblastic leukemia (T-ALL) when used in conjunction with Methotrexate. Additionally, (+)SHIN2 features an alkyne group that facilitates its use in click chemistry applications, allowing for copper-catalyzed azide-alkyne cycloaddition (CuAAc) with azide-containing molecules.

SHMT-IN-2 is a stereospecific inhibitor of human serine hydroxymethyltransferases SHMT1 and SHMT2, exhibiting IC50 values of 13 nM and 66 nM, respectively. This compound effectively inhibits the proliferation of various human cancer cell lines and demonstrates notable sensitivity towards B-cell lymphomas. SHMT-IN-2 serves as a valuable tool for research investigating metabolic pathways involved in cancer cell growth and treatment response.

SHMT-IN-1 is a potent inhibitor of plasmodial serine hydroxymethyltransferase (SHMT). This compound demonstrates significant antitumor activity, making it a valuable tool for research focused on cancer therapeutics and metabolic pathways. Its efficacy in inhibiting SHMT highlights its potential application in the study of malaria and related biological processes.

SHMT-IN-3 is a selective inhibitor of serine hydroxymethyltransferases SHMT1 and SHMT2, with an IC50 of 0.53 µM for human SHMT1. This compound demonstrates noncompetitive inhibition against serine, making it a valuable tool for studying metabolic pathways involving one-carbon metabolism. SHMT-IN-3 is useful for investigating the role of SHMT in various biological processes and may have applications in cancer research and other metabolic disorders.

SHMT-IN-4 is an inhibitor of serine hydroxymethyltransferase (SHMT1), demonstrating an IC50 value of 193.8 g a.i./ha. This compound interferes with amino acid synthesis and metabolism in plants by binding to SHMT1, leading to inhibited plant growth. Importantly, SHMT-IN-4 exhibits minimal toxicity to maize and honeybees, making it a viable option for agricultural research applications focusing on selective herbicide development.