TH5427 hydrochloride 

TH5427 hydrochloride is a NUDT5 inhibitor with a human target IC₅₀ of 29 nM, ~690-fold selectivity over MTH1 in vitro, and selective functional inhibition over other NUDIX hydrolases including NUDT9^[1].TH5427 hydrochloride binds to the active site of NUDT5, blocking enzymatic activity related to ADP-ribose metabolism and PAR-derived ATP synthesis^[1].TH5427 hydrochloride blocks progestin-dependent nuclear ATP synthesis, impairs progestin-induced chromatin remodeling, inhibits histone H1 displacement, disrupts progestin-dependent gene regulation, and abrogates progestin-dependent proliferation in breast cancer cells^[1].TH5427 hydrochloride functions as a versatile probe to study nuclear ATP dynamics and ADP-ribose-related metabolism in cells^[1].TH5427 hydrochloride engages NUDT5 at physiological temperatures, as demonstrated by Drug Affinity Responsive Target Stability (DARTS) assay^[1].TH5427 hydrochloride stabilizes NUDT5 against thermal denaturation in cell lysates and intact cells, as shown by cellular thermal shift assay (CETSA)^[1].TH5427 hydrochloride functionally inhibits NUDT5 activity, leading to downstream effects on oxidative DNA damage and DNA replication in triple-negative breast cancer (TNBC) cells^[2].TH5427 hydrochloride suppresses proliferation of TNBC cells without inducing cell death or apoptosis, slows DNA replication in TNBC cells, promotes accumulation of oxidative DNA lesions, and triggers DNA damage response in TNBC cells^[2].TH5427 hydrochloride suppresses growth of TNBC cells in vitro, inhibits growth of TNBC xenograft tumors in nude mice in vivo, and shows greater potency against TNBC cell lines compared to ER-positive and normal-like breast cell lines^[2].TH5427 hydrochloride can be used for the research of breast cancer and triple-negative breast cancer^[1][2].

TH5427 hydrochloride (29 nM; 30 min; RT) potently inhibits purified human NUDT5 protein in an enzyme-coupled malachite green assay, with an IC₅₀ of 29 nM^[1].
TH5427 hydrochloride (0.06-20 μM; 3 h; 37°C) dose-dependently stabilizes NUDT5 in intact HL-60 acute promyelocytic leukemia cells, with an apparent EC₅₀ of 2.1 μM^[1].
The IC₅₀ values of TH5427 hydrochloride in triple-negative breast cancer (TNBC) cell lines MDA-MB-231, MDA-MB-436, MDA-MB-468 and BT-20 are significantly lower than those in estrogen receptor (ER)-positive and normal-like breast cell lines^[2].
TH5427 hydrochloride (10 μM; 48 h) does not induce apoptosis in the ER-positive breast cancer cell line MCF7 or the triple-negative breast cancer (TNBC) cell line MDA-MB-231^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

TH5427 (50 mg/kg; i.p.; 5 times per week) hydrochloride significantly reduces triple-negative breast cancer xenograft growth rate and tumor cell proliferation in nude mice^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

527.79

C₂₀H₂₁Cl₃N₈O₃

2253744-57-7

[H]Cl.O=C(N1C)N(C)C2=C(N(CC3=NN=C(C4=CC=C(Cl)C(Cl)=C4)O3)C(N5CCNCC5)=N2)C1=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Page BDG, et al. Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells. Nat Commun. 2018;9(1):250. Published 2018 Jan 17.  [Content Brief]

  [2]. Qian J, et al. The novel phosphatase NUDT5 is a critical regulator of triple-negative breast cancer growth. Breast Cancer Res. 2024;26(1):23. Published 2024 Feb 5.