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Purity: ≥98%
Domatinostat (formerly known as 4SC-202) is a novel class I HDAC inhibitor (HDACi) that potently inhibited survival and proliferation of primary human colon cancer cells and established CRC lines (HT-29, HCT-116, HT-15, and DLD-1). It has IC50 values of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. Additionally, dominatinostat exhibits inhibitory activity against LSD1, or lysine specific demethylase 1. CRC cells were exposed to 4SC-202, which induced apoptosis activation; however, the cytotoxicity of 4SC-202 was considerably reduced in CRC cells by caspase inhibitors (z-VAD-CHO and z-DVED-CHO). Concurrently, 4SC-202 caused a significant G2-M arrest in CRC cells. AKT activation may be a significant resistance factor for 4SC-202, according to more research. The cytotoxicity of 4SC-202 was significantly enhanced in CRC cells by serum starvation, AKT inhibition (with perifosine or MK-2206), or AKT1-shRNA knockdown. Conversely, in HT-29 cells, constitutively active AKT1 (CA-AKT1) expressed exogenously reduced sensitivity by 4SC-202. Notably, 4SC-202 increased in vitro anti-CRC activity induced by oxaliplatin at a low concentration. We demonstrated that oral gavage of 4SC-202 inhibited HT-29 xenograft growth in nude mice in vivo, and that its activity was enhanced when combined with oxaliplatin. All of these pre-clinical findings suggest that 4SC-202 could be a worthwhile anti-CRC medication and chemoadjuvant that is worth more research.
| 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 )
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| ln Vitro |
Domatinostat tosylate suppresses clonogenic growth, induces caspase activity, and dramatically decreases the proliferation of all epithelial and mesenchymal UC cell lines (IC50 0.15-0.51 μM)[1]. In colorectal cancer (CRC) cells, domatinostat tosylate activates apoptosis, but caspase inhibitors (z-VAD-CHO and z-DVED-CHO) dramatically reduce the cytotoxicity that domatinostat tosylate causes in CRC cells. In the meantime, CRC cells experience a sharp G2-M arrest due to domatinostat tosylate. Additional research indicates that AKT activation may be a significant Domatinostat tosylate resistance factor. The cytotoxicity of domatinostat tosylate is significantly enhanced in colorectal cancer cells by serum starvation, AKT inhibition (with perifosine or MK-2206), or AKT1-shRNA knockdown. In contrast, constitutively active AKT1 (CA-AKT1) expressed exogenously reduces the HT-29 cells' sensitivity to dometinostat tosylate. Notably, oxaliplatin-induced in vitro anti-CRC activity is enhanced by domatinostat tosylate at low concentrations[2]. Strong cytotoxic and proliferation-inhibitory effects are induced against patient-derived primary HCC cells as well as established HCC cell lines (HepG2, HepB3, SMMC-7721) by domatinosal tosylate treatment. Apoptosis signal-regulating kinase 1 (ASK1) is activated by domatinostat tosylate, which results in its translocation to mitochondria and physical association with Cyp-D[3].
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| ln Vivo |
Domatinostat tosylate, when administered orally, inhibits the growth of HT-29 xenografts in nude mice. This effect is enhanced when oxaliplatin is added[2].
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| References |
| Molecular Formula |
C₃₀H₂₉N₅O₆S₂
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| Molecular Weight |
619.71
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| Exact Mass |
619.16
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| CAS # |
1186222-89-8
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| Related CAS # |
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| Appearance |
Powder
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| SMILES |
CC1=CC=C(C=C1)S(=O)(=O)O.CN1C=C(C=N1)C2=CC=C(C=C2)S(=O)(=O)N3C=CC(=C3)/C=C/C(=O)NC4=CC=CC=C4N
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| InChi Key |
IAVXAZDVNICKFJ-ICSBZGNSSA-N
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| InChi Code |
InChI=1S/C23H21N5O3S.C7H8O3S/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;1-6-2-4-7(5-3-6)11(8,9)10/h2-16H,24H2,1H3,(H,26,29);2-5H,1H3,(H,8,9,10)/b11-6+;
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| Chemical Name |
(E)-N-(2-aminophenyl)-3-[1-[4-(1-methylpyrazol-4-yl)phenyl]sulfonylpyrrol-3-yl]prop-2-enamide;4-methylbenzenesulfonic acid
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.03 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 (4.03 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6137 mL | 8.0683 mL | 16.1366 mL | |
| 5 mM | 0.3227 mL | 1.6137 mL | 3.2273 mL | |
| 10 mM | 0.1614 mL | 0.8068 mL | 1.6137 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.
 Impact of specific pharmacological inhibition of class I HDAC isoenzymes with 4SC-202 on UCCs and control cells.Target Oncol.2016 Dec;11(6):783-798. |
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 Morphology, clonogenicity and senescence following 4SC-202 treatment in UCCs and control cells.Target Oncol.2016 Dec;11(6):783-798. |
 Mechanisms of cell death upon 4SC-202 treatment in UCCs and control cells.Target Oncol.2016 Dec;11(6):783-798. |
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