Zavondemstat

Zavondemstat
Clinical data
Drug class	KDM4 inhibitor
Identifiers
	IUPAC name 3-[[(4R)-7-(N-methyl-4-propan-2-ylanilino)-3,4-dihydro-2H-chromen-4-yl]methylamino]pyridine-4-carboxylic acid;
CAS Number	1851412-93-5;
PubChem CID	118597685;
DrugBank	DB21608;
ChemSpider	128922294;
UNII	4L3YJL2P4P;
ChEMBL	ChEMBL5314494;
Chemical and physical data
Formula	C26H29N3O3
Molar mass	431.536 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)C1=CC=C(C=C1)N(C)C2=CC3=C(C=C2)[C@@H](CCO3)CNC4=C(C=CN=C4)C(=O)O;
	InChI InChI=1S/C26H29N3O3/c1-17(2)18-4-6-20(7-5-18)29(3)21-8-9-22-19(11-13-32-25(22)14-21)15-28-24-16-27-12-10-23(24)26(30)31/h4-10,12,14,16-17,19,28H,11,13,15H2,1-3H3,(H,30,31)/t19-/m0/s1; Key:NDVITLLKZQXKGU-IBGZPJMESA-N;

Zavondemstat (TACH101, QC8222) is a drug which acts as an inhibitor of the enzyme lysine-specific demethylase 4 (KDM4). It is described as a pan-KDM4 inhibitor, being active at all four isoforms KDM4A, KDM4B, KDM4C and KDM4D, which show functional redundancy so older inhibitors selective for just one isoform have failed to be effective. Zavondemstat is being researched for the treatment of certain forms of cancer and is in early stage clinical trials.^[1]^[2]^[3]^[4]

References

^ Chandhasin C, Dang V, Perabo F, Del Rosario J, Chen YK, Filvaroff E, et al. (November 2023). "TACH101, a first-in-class pan-inhibitor of KDM4 histone demethylase". Anti-Cancer Drugs. 34 (10): 1122–1131. doi:10.1097/CAD.0000000000001514. PMC 10569680. PMID 37067993.
^ Chandhasin C, Perabo F, Dai Y, DiMascio L, Mehta RK, Hassan MK, Nyati MK. 245 (PB233): Histone methylation changes of H3K9 and H3K36 in PBMCs as pharmacodynamic biomarkers for Zavondemstat (TACH101), a paninhibitor of KDM4 histone lysine demethylase. European Journal of Cancer 2024; 211: 114763.
^ Tsimberidou AM, Dayyani F, Sommerhalder D, Vandross AL, Pelster MS, Henry JT, et al. (July 2025). "Phase 1 study of zavondemstat (TACH101), a first-in-class KDM4 inhibitor, in patients with advanced solid tumors". The Oncologist. 30 (7) oyaf169. doi:10.1093/oncolo/oyaf169. PMC 12236304. PMID 40580997.
^ Yang X, Han Y, Yu L, Xu S (January 2026). "A patent review of KDM4 histone demethylase inhibitors (2014-present)". Expert Opinion on Therapeutic Patents: 1–17. doi:10.1080/13543776.2026.2614491. PMID 41504014.

[1] Chandhasin C, Dang V, Perabo F, Del Rosario J, Chen YK, Filvaroff E, et al. (November 2023). "TACH101, a first-in-class pan-inhibitor of KDM4 histone demethylase". Anti-Cancer Drugs. 34 (10): 1122–1131. doi:10.1097/CAD.0000000000001514. PMC 10569680. PMID 37067993.

[2] Chandhasin C, Perabo F, Dai Y, DiMascio L, Mehta RK, Hassan MK, Nyati MK. 245 (PB233): Histone methylation changes of H3K9 and H3K36 in PBMCs as pharmacodynamic biomarkers for Zavondemstat (TACH101), a paninhibitor of KDM4 histone lysine demethylase. European Journal of Cancer 2024; 211: 114763.

[3] Tsimberidou AM, Dayyani F, Sommerhalder D, Vandross AL, Pelster MS, Henry JT, et al. (July 2025). "Phase 1 study of zavondemstat (TACH101), a first-in-class KDM4 inhibitor, in patients with advanced solid tumors". The Oncologist. 30 (7) oyaf169. doi:10.1093/oncolo/oyaf169. PMC 12236304. PMID 40580997.

[4] Yang X, Han Y, Yu L, Xu S (January 2026). "A patent review of KDM4 histone demethylase inhibitors (2014-present)". Expert Opinion on Therapeutic Patents: 1–17. doi:10.1080/13543776.2026.2614491. PMID 41504014.

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