MTH1

(S)-crizotinib, the (S)-enantiomer of crizotinib, is a potent MTH1 (NUDT1) inhibitor with IC50 of 72 nM.

TH287 is a potent inhibitor of MTH1 (NUDT1) with an IC50 value of 0.8 nM, less potent for MTH2, NUDT5, NUDT12, NUDT14, and NUDT16,

TH588 is first-in-class nudix hydrolase family inhibitor that potently and selectively engage and inhibit the MTH1(IC50= 5 nM) in cells,

BAY-707 is a potent and selective inhibitor of MTH1 (NUDT1) that functions through a substrate-competitive mechanism with an IC50 of 2.3 nM. This compound exhibits a favorable pharmacokinetic profile compared to other MTH1 inhibitors and demonstrates good tolerability in mouse models. Although BAY-707 has shown effective inhibition of MTH1, it does not exhibit significant anticancer activity in either in vitro or in vivo studies, making it suitable for research into MTH1 function and related pathways.

MTH1 activator-1 is a potent activator of MTH1, a critical enzyme involved in the repair of oxidative damage to nucleotide pools. This compound significantly enhances endogenous MTH1 activity, leading to reduced levels of 8-oxo-dG in cellular DNA. MTH1 activator-1 serves as a valuable tool for investigating the cellular and biological implications of enhanced oxidative damage repair, and it may provide insights into strategies for delaying or preventing tumorigenesis.

aTAG 4531 is a selective MTH1 degrader that exerts its action through the formation of a ternary complex with MTH1, CRBN E3 ligase, and the degrader itself. It displays a DC50 value of 0.28 nM and a Ki value of 1.8 nM, highlighting its potent degradation capability. This compound is valuable for research focused on MTH1 inhibition and subsequent cellular effects, offering insights into its role in cancer biology and related therapeutic applications.

TH287 hydrochloride is a highly potent and selective inhibitor of MTH1, exhibiting an IC50 of 0.8 nM. It demonstrates significant selectivity for MTH1 over related enzymes, showing no relevant inhibition of MTH2, NUDT5, NUDT12, NUDT14, NUDT16, dCTPase, dUTPase, and ITPA at concentrations of 100 µM. This compound is valuable for cancer research, particularly in the exploration of novel chemotherapeutic strategies targeting MTH1's role in tumor metabolism.

8-Oxo-dGTP (8-Oxo-Deoxyguanosine triphosphate) is a reactive oxidized guanine nucleotide that serves as a substrate for MTH1 and other pyrophosphohydrolases. This compound is known to act as a mutagen, integrating into DNA and leading to A:T to C:G transversions, which can contribute to genomic instability. Additionally, 8-Oxo-dGTP can provoke oxidative DNA modifications, strand breaks, and the promotion of apoptosis, particularly in mth1-deficient organisms. Its accumulation is linked to various biological processes and is extensively utilized in research on carcinogenesis, neurodegenerative diseases, and other pathologies.

MTH1-IN-2 is an inhibitor of MutT homolog 1 (MTH1), a target implicated in cancer biology. This compound exhibits significant anti-tumor activity, making it a valuable tool for cancer research. MTH1-IN-2 can be utilized to investigate the mechanisms of tumorigenesis and to develop therapeutic strategies that exploit the MTH1 pathway.

IACS-4619 is a highly selective inhibitor of the MTH1 enzyme (MutT homolog 1) with an IC50 of 0.2 nM. This 2-aminopyrimidine compound effectively blocks the hydrolysis of oxidized purine nucleotides, such as 8-oxo-dGTP, preventing the incorporation of these nucleotides into DNA. Notably, IACS-4619 demonstrates significant inhibition of endogenous MTH1 activity in MTH1-overexpressing U2OS cells without exhibiting antiproliferative or cytotoxic effects on various human cancer and normal cell lines. This reagent is applicable in oncology research targeting the MTH1 pathway.

SU0383 is a dual inhibitor of MTH1 and OGG1, demonstrating IC50 values of 0.034 μM and 0.49 μM, respectively. This compound induces cytotoxicity in cancer cells and enhances their sensitivity to oxidative stress, while exhibiting minimal toxicity in normal cells. SU0383 is suitable for applications in cancer research, particularly in studies focused on oxidative stress responses and therapeutic strategies targeting DNA repair mechanisms.

aTAG 2139 is a selective degrader targeting MTH1 via an aTAG-based mechanism. It demonstrates biological activity with a DC50 value of 1.1 nM and a Ki value of 2.1 nM for MTH1 inhibition. This compound is suitable for studies investigating the role of MTH1 in various cellular processes and therapeutic applications in cancer research.

MTH1 Ligand 1 is a specific ligand that targets the MTH1 protein, playing a crucial role in cellular pathways associated with nucleotide metabolism and cancer cell survival. This compound is instrumental in the synthesis of PROTAC aTAG 2139, facilitating targeted protein degradation in research applications. Its selectivity for MTH1 makes it a valuable tool for investigating therapeutic strategies aimed at mitigating oncogenic processes.

MTH1 degrader-1 is a potent degrader targeting MTH1 through a PROTAC mechanism. This compound facilitates the selective degradation of MTH1, making it a valuable tool for studying the role of MTH1 in cancer metabolism and therapy resistance. Key applications include the development of PROTACs and the synthesis of related compounds, such as PROTAC aTAG 4531.

IACS-4759 is a potent and selective inhibitor of MTH1 (MutT homolog 1), with an IC50 value of 0.6 nM. This compound exhibits significant anti-cancer activity by disrupting the repair of damaged nucleotides, thereby inducing metabolic stress in cancer cells. IACS-4759 is useful for research applications focused on cancer metabolism and the development of targeted cancer therapies.