Zavondemstat, also known as TACH101, and QC8222 is a selective pan-inhibitor of histone lysine demethylase 4 (KDM4). It inhibits KDM4 enzymes with low nanomolar IC₅₀ values, typically around 10–20 nM in biochemical assays. Zavondemstat blocks demethylation of H3K9me3 and H3K36me3 histone marks, leading to repression of oncogenic transcription programs. In preclinical cancer models, it induces cell cycle arrest and apoptosis, particularly in tumors with KDM4 overexpression, such as colorectal, breast, and prostate cancers. In vitro, it inhibits proliferation of cancer cell lines with GI₅₀ values in the range of 30–100 nM, depending on cell type. In vivo, Zavondemstat achieves strong tumor growth inhibition in xenograft models at well-tolerated oral doses, with clear target engagement (measured by sustained increases in H3K9me3 levels). It’s currently advancing through clinical trials aimed at treating advanced solid tumors and hematologic malignancies where KDM4 dysregulation drives disease.
MedKoo Cat#: 130517
Name: Zavondemstat
CAS#: 1851412-93-5 (free acid)
Chemical Formula: C26H29N3O3
Exact Mass: 431.2209
Molecular Weight: 431.54
Elemental Analysis: C, 72.37; H, 6.77; N, 9.74; O, 11.12
The following data is based on the product molecular weight 431.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
