| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
Histone deacetylases (HDACs); HDAC1 (IC50 = 110 nM); HDAC2 (IC50 = 154 nM); HDAC3 (IC50 = 143 nM)
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|---|---|
| ln Vitro |
YSR734 is a first-in-class covalent HDACi, with a 2-aminobenzanilide Zn2+ chelate and a pentafluorobenzenesulfonamide electrophile. This class I selective proof of concept modified HDAC2Cys274 (catalytic domain), with nM potency against HDAC1-3, sub-μM activity in MV4-11 cells, and limited cytotoxicity in MRC-9 fibroblasts. In C2C12 myoblasts, YSR734 activated muscle-specific biomarkers myogenin/Cav3, causing potent differentiation into myotubes (applications in Duchenne Muscular Dystrophy). [1]
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| Cell Assay |
W estern-Blot analysis of Ac-Histone H3, and Ac-α-tubulin in MV4-11 AML cells using increasing concentrations of MS275, CovHDACi YSR734, and para-H negative control 23(GF608). Inhibitor treatment for 6 hbefore cellular washout and 16 hincubation prior to blotting. HSC70 used as a loading control[1].
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| References | |
| Additional Infomation |
Histone deacetylases (HDACs) have emerged as powerful epigenetic modifiers of histone/non-histone proteins via catalyzing the deacetylation of ε-N-acetyl lysines. The dysregulated activity of these Zn2+-dependent hydrolases has been broadly implicated in disease, notably cancer. Clinically, the recurring dose-limiting toxicities of first-generation HDACi sparked a paradigm shift toward safer isoform-specific molecules. With pervasive roles in aggressive diseases, there remains a need for novel approaches to target these enzymes. Herein, we report the discovery of YSR734, a first-in-class covalent HDACi, with a 2-aminobenzanilide Zn2+ chelate and a pentafluorobenzenesulfonamide electrophile. This class I selective proof of concept modified HDAC2Cys274 (catalytic domain), with nM potency against HDAC1-3, sub-μM activity in MV4-11 cells, and limited cytotoxicity in MRC-9 fibroblasts. In C2C12 myoblasts, YSR734 activated muscle-specific biomarkers myogenin/Cav3, causing potent differentiation into myotubes (applications in Duchenne Muscular Dystrophy). Current efforts are focused on improving in vivo ADME toward a preclinical covalent HDACi.[1]
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| Molecular Formula |
C26H23F5N4O5S
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|---|---|
| Molecular Weight |
598.54
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| Exact Mass |
598.13093
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| CAS # |
3032969-58-4
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| PubChem CID |
170453116
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| Appearance |
White to off-white solid powder
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| LogP |
3.5
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| InChi Key |
JGJZNWDPKNHILY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H23F5N4O5S/c27-19-20(28)22(30)24(23(31)21(19)29)41(38,39)35-11-9-16(10-12-35)40-26(37)33-13-14-5-7-15(8-6-14)25(36)34-18-4-2-1-3-17(18)32/h1-8,16H,9-13,32H2,(H,33,37)(H,34,36)
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| Chemical Name |
[1-(2,3,4,5,6-pentafluorophenyl)sulfonylpiperidin-4-yl] N-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]carbamate
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| Synonyms |
YSR734; YSR-734; YSR 734
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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 |
| 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) |
DMSO :~100 mg/mL (~167.07 mM; with sonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (8.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 50.0 mg/mL clear DMSO stock solution and add it to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6707 mL | 8.3537 mL | 16.7073 mL | |
| 5 mM | 0.3341 mL | 1.6707 mL | 3.3415 mL | |
| 10 mM | 0.1671 mL | 0.8354 mL | 1.6707 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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