| Size | Price | Stock | Qty |
|---|---|---|---|
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Domatinostat (formerly 4SC-202) is a novel, potent, and orally bioavailable benzamide-based Class I HDAC inhibitor with potential anticancer activity. It has IC50 values of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3 inhibition, respectively. In order to cause an accumulation of highly acetylated histones, domatinostat/4SC-202 selectively binds to and inhibits class I HDACs.
| Targets |
HDAC-3 ( IC50 = 0.57 μM ); HDAC-2 ( IC50 = 1.12 μM ); HDAC-1 ( IC50 = 1.2 μM ); HDAC-11 ( IC50 = 9.7 μM ); HDAC-5 ( IC50 = 11.3 μM ); HDAC-10 ( IC50 = 21 μM ); HDAC-9 ( IC50 = 50 μM )
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Cell Assay |
Treatment with domatinostat (4SC-202 free base) tosylate has strong cytotoxic and proliferation-inhibitory effects on patient-derived primary HCC cells as well as established HCC cell lines (HepG2, HepB3, SMMC-7721). As a result of the activation of apoptosis signal-regulating kinase 1 (ASK1) induced by domatinostat (4SC-202 free base), it translocates to mitochondria and physically associates with Cyp-D.
|
|
| Animal Protocol |
A549 NSCLC xenograft model and RKO27 colon carcinoma model
120 mg/kg p.o. |
|
| References | ||
| Additional Infomation |
4SC-202 has been used in trials studying the treatment of Advanced Hematologic Malignancies.
Domatinostat is an orally bioavailable benzamide and inhibitor of human class I histone deacetylases (HDACs) isoenzymes 1, 2 and 3, with potential antineoplastic activity. Domatinostat selectively binds to and inhibits class I HDACs leading to an accumulation of highly acetylated histones. This may result in an induction of chromatin remodeling, the selective transcription of tumor suppressor genes, and the tumor suppressor protein-mediated inhibition of tumor cell division and eventually the induction of tumor cell apoptosis. This may inhibit tumor cell proliferation in susceptible tumor cells. HDACs, upregulated in many tumor types, are a class of enzymes that deacetylate chromatin histone proteins. |
| Molecular Formula |
C23H21N5O3S
|
|---|---|
| Molecular Weight |
447.51
|
| Exact Mass |
447.136
|
| Elemental Analysis |
C, 61.73; H, 4.73; N, 15.65; O, 10.73; S, 7.17
|
| CAS # |
910462-43-0
|
| Related CAS # |
1186222-89-8
|
| PubChem CID |
15985904
|
| Appearance |
White to khaki solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Index of Refraction |
1.672
|
| LogP |
2.63
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
775
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(C1C=CC(C2C=NN(C)C=2)=CC=1)(N1C=CC(/C=C/C(=O)NC2C=CC=CC=2N)=C1)(=O)=O
|
| InChi Key |
PRXXYMVLYKJITB-IZZDOVSWSA-N
|
| InChi Code |
InChI=1S/C23H21N5O3S/c1-27-16-19(14-25-27)18-7-9-20(10-8-18)32(30,31)28-13-12-17(15-28)6-11-23(29)26-22-5-3-2-4-21(22)24/h2-16H,24H2,1H3,(H,26,29)/b11-6+
|
| Chemical Name |
(E)-N-(2-aminophenyl)-3-[1-[4-(1-methylpyrazol-4-yl)phenyl]sulfonylpyrrol-3-yl]prop-2-enamide
|
| Synonyms |
domatinostat; 4SC202; 4SC 202; 4SC-202
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 10 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2346 mL | 11.1729 mL | 22.3459 mL | |
| 5 mM | 0.4469 mL | 2.2346 mL | 4.4692 mL | |
| 10 mM | 0.2235 mL | 1.1173 mL | 2.2346 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04393753 | Active Recruiting |
Drug: domatinostat in combination with avelumab |
Merkel Cell Carcinoma | 4SC AG | September 1, 2020 | Phase 2 |
| NCT04133948 | Active Recruiting |
Drug: Domatinostat Drug: Nivolumab |
Malignant Melanoma Stage III | The Netherlands Cancer Institute |
January 7, 2020 | Phase 1 Phase 2 |
| NCT04874831 | Withdrawn | Drug: domatinostat in combination with avelumab |
Merkel Cell Carcinoma | 4SC AG | November 1, 2021 | Phase 2 |
|
|---|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
