TH-407a 

TH-407a is an orally active and selective USP15 inhibitor with an IC₅₀ of 0.76 μM. As an allosteric modulator, TH-407a binds to a non-catalytic site to block deubiquitinating activity. TH-407a inhibits cell growth, proliferation, clonogenicity and migration, regulates the p53 signaling pathway, and reduces the stability of PARP1. TH-407a exhibits anti-tumor activity in breast cancer xenograft mouse models. TH-407a can be used for the research of breast cancer^[1].

TH-407a potently inhibits the enzymatic activity of purified USP15 protein with an IC₅₀ of 0.76 μM via Ub-AMC hydrolysis inhibition^[1].
TH-407a (0.31-20 μM; 30 min) dose-dependently inhibits recombinant USP15-mediated hydrolysis of K48-linked diubiquitin^[1].
TH-407a inhibits the interaction between USP15 protein and the covalent-binding ubiquitin analog Ub-PA in vitro^[1].
TH-407a is selective for USP15, showing negligible inhibition of purified USP1, USP2, and USP7 proteins at 10 μM^[1].
TH-407a (10× IC₅₀; 30, 60, or 90 min) reversibly inhibits purified USP15 protein, with time-dependent recovery of enzymatic activity after dilution^[1].
TH-407a (1.5625-12.5 μM) directly binds to immobilized USP15 protein with strong affinity, as demonstrated by a K_d of 4.26 μM via SPR^[1].
TH-407a dose-dependently inhibits the proliferation of MCF-7, HCC70, MDA-MB-231, and MDA-MB-436 breast cancer cells, with IC₅₀ values of 19.57 μM for MCF-7 and 38.66 μM for MDA-MB-436^[1].
TH-407a (5-10 μM) inhibits clonal growth of MCF-7, HCC70, MDA-MB-231, and MDA-MB-436 breast cancer cells^[1].
TH-407a (10 μM (HCC70, MDA-MB-231); 20 μM (MCF-7, MDA-MB-436); 12 or 24 h) impairs the migratory capacity of MCF-7, HCC70, MDA-MB-231, and MDA-MB-436 breast cancer cells^[1].
TH-407a (5-40 μM (immunoblotting); 20 μM (MDM2 ubiquitination assessment)) modulates the p53 signaling pathway in MCF-7 breast cancer cells by downregulating MDM2, stabilizing p53, and increasing MDM2 ubiquitination^[1].
TH-407a (5-40 μM (immunoblotting); 10 μM (CHX stability assay); 4 or 12 h (pre-treatment); 0-12 h (monitoring)) reduces PARP1 protein stability and expression in MCF-7, HCC70, MDA-MB-231, and MDA-MB-436 breast cancer cells by increasing PARP1 ubiquitination and accelerating its degradation^[1].

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

TH-407a (100 mg/kg; p.o.; daily; 12 days) potently reduces MCF-7 breast cancer xenograft tumor weight by ~50% in nude mice^[1].
TH-407a (100 mg/kg; p.o.; daily; 12 days) significantly reduces MDA-MB-436 breast cancer xenograft tumor growth in nude mice^[1].

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

354.40

C₂₂H₁₈N₄O

1903103-73-0

[H]C1(CN(C(C2=CC=C3C(C=CC=C3)=C2)=O)C1)N4N=NC(C5=CC=CC=C5)=C4

Room temperature in continental US; may vary elsewhere.

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

• [1]. Zhang T, et al.. Discovery of a potent and selective small-molecule inhibitor of ubiquitin-specific peptidase 15 (USP15) for the treatment of breast cancer. European journal of medicinal chemistry. 2026 May 25;316:119005.