Zavondemstat

Zavondemstat (QC8222) is an orally active, selective inhibitor of the histone lysine demethylase 4 (KDM4) family, with an IC₅₀ of ≤ 0.08 μM against human KDM4A–D and a K₊₀ of 0.52 μM against human KDM4C. Zavondemstat activates tumor suppressor genes, induces apoptosis, causes S-phase cell cycle arrest, and inhibits cancer cell proliferation. In in vivo studies, Zavondemstat inhibits tumor growth and induces tumor regression. Zavondemstat can be used in cancer research.

KDM4 isoforms A-D:80 nM, KDM5 family members:140-400 nM

Methods: MDA-MB-231 cells were treated with TACH101 (0.01, 0.1 μmol/L) and cultured for 48 h and 72 h; cell cycle analysis was performed using PI staining and flow cytometry.
Results: Zavondemstat induces S-phase cell cycle arrest in MDA-MB-231 cells. [1]
Methods: Jurkat, MDA-MB-231, KYSE-150, MM.1s, HL-60, HT-29, MCF-7, LOUCY, and IMR-90 cell lines were treated with Zavondemstat (0.0005–10 μmol/L) and cultured for 7 days; cell proliferation was assessed using the BrdU incorporation assay, MTS assay, and CellTiter-Glo assay.
Results: Zavondemstat potently inhibited the proliferation of multiple cancer cell lines, with IC₅₀ values ranging from 0.0027 to 0.037 μM, while exhibiting lower activity against normal IMR-90 fibroblasts [1].

Methods: In a colorectal cancer PDX model in NSG mice, following successful tumor implantation, Zavondemstat (TACH101) (10, 20 mg/kg) was administered orally once daily for 3 weeks.
Results: Zavondemstat (TACH101) inhibited tumor growth in a dose-dependent manner. [1]
Methods: A CDX model of esophageal squamous cell carcinoma was established in nude mice. Following successful implantation, Zavondemstat (TACH101) (10, 15, 20 mg/kg) was administered orally once daily for 3 weeks.
Results: Zavondemstat (TACH101) effectively inhibited tumor growth in a dose-dependent manner. [1]

DMSO: 7.25 mg/mL (16.8 mM), Sonication and heating are recommended.