| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Histone lysine demethylase 4 (KDM4) family, specifically KDM4A, KDM4B, KDM4C, and KDM4D (also known as KDM4 isoforms). (S)-Zavondemstat selectively targets KDM4A-D with no effect on other KDM families. It competes with the co-substrate alpha-ketoglutarate (alpha-KG) for binding to the active site of KDM4.
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| ln Vitro |
Zavondemstat, the active parent compound, is an orally active pan-KDM4 inhibitor with an IC50 ≤ 0.08 uM against human KDM4A-D and a Ki of 0.52 uM against human KDM4C. It induces cell apoptosis, causes S-phase cell cycle arrest, reduces the population of tumor-initiating cells, and inhibits cancer cell proliferation in vitro in various cancer cell lines and organoid models.
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| ln Vivo |
Zavondemstat, the parent compound, suppresses tumor growth and induces tumor regression in mouse xenograft models. In a Phase 1 clinical study (NCT05076552) in patients with heavily pretreated advanced metastatic cancers, Zavondemstat was very well tolerated and showed encouraging preliminary clinical benefit. It demonstrated a dose-proportional exposure profile with a half-life of about 1.5 hours and no to minimal drug accumulation.
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| Enzyme Assay |
Typical KDM4 inhibition assay: incubate recombinant human KDM4C (0.5-2 ug) with 50 mM HEPES pH 7.5, 1 mM alpha-ketoglutarate, 2 mM ascorbate, 50 uM (NH4)2Fe(SO4)2, 0.5 mM TCEP, 0.1 mg/mL BSA, and 10 uM biotinylated H3K9me3 peptide in a total volume of 50 uL at 37degC for 1 hour. Zavondemstat is added at varying concentrations (0.01-10 uM). The reaction is stopped, and demethylation is detected by ELISA using an H3K9me3-specific antibody.
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| Cell Assay |
Standard cell viability protocol: culture cancer cell lines (e.g., HCT116 colorectal, KYSE150 esophageal) in RPMI-1640+10% FBS in 96-well plates. Treat with a dose range of Zavondemstat (0.001-10 uM) for 72 hours. Cell viability is assessed using CellTiter-Glo luminescent assay. Apoptosis is measured by Annexin V-FITC/PI staining followed by flow cytometry. S-phase arrest is measured by propidium iodide staining and cell cycle analysis.
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| Animal Protocol |
Mouse xenograft models: establish subcutaneous xenografts of HCT116 cells (5×10⁶ cells/injection) in nude mice. When tumors reach ~150 mm3, administer Zavondemstat orally at doses ranging from 3 to 30 mg/kg once daily for 21-28 days. Tumor volume is measured twice weekly, and tumors are harvested for immunohistochemical analysis of KDM4 activity and histone methylation markers.
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| ADME/Pharmacokinetics |
In clinical Phase 1 study (NCT05076552) in patients with advanced solid tumors, Zavondemstat demonstrated a dose-proportional exposure profile with a half-life (t1/2) of about 1.5 hours. There was no to minimal drug accumulation observed with repeated daily dosing.
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| Toxicity/Toxicokinetics |
In a Phase 1 clinical study, Zavondemstat was reported to be very well tolerated with a favorable safety profile. No specific dose-limiting toxicities were observed at the tested doses. Comprehensive preclinical toxicology data for (S)-Zavondemstat alone are not published, but the parent compound showed manageable adverse events with no significant myelosuppression in early trials.
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| References | |
| Additional Infomation |
Zavondemstat is the first KDM4 inhibitor to enter clinical development (Phase 1, NCT05076552). (S)-Zavondemstat is the S-enantiomer of the parent compound, supplied for research use with purity ≥98%. Molecular formula: C26H29N3O3, molecular weight: 431.53. It is indicated for research applications in epigenetics and oncology. Each product in one row, fields tab-separated.
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| Molecular Formula |
C26H29N3O3
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| Molecular Weight |
431.53
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| Related CAS # |
Zavondemstat;1851412-93-5;Zavondemstat L-lysine
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| Appearance |
Light yellow to light brown solid powder
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| Synonyms |
(S)-QC8222 free base; (S)-TACH 101 free base
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3173 mL | 11.5867 mL | 23.1734 mL | |
| 5 mM | 0.4635 mL | 2.3173 mL | 4.6347 mL | |
| 10 mM | 0.2317 mL | 1.1587 mL | 2.3173 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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