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| 10mg |
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| Targets |
Histone deacetylases (HDACs); HDAC1 (IC50 = 110 nM); HDAC2 (IC50 = 154 nM); HDAC3 (IC50 = 143 nM)
YSR734 targets histone deacetylases (HDACs), specifically HDAC1, HDAC2, and HDAC3, which are Class I HDACs involved in the regulation of gene expression through histone deacetylation. As a covalent HDAC inhibitor, YSR734 forms an irreversible bond with its target enzymes, leading to sustained inhibition of HDAC activity. The compound features a pentafluorobenzene sulfonamide electrophile that enables covalent binding to the target. |
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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]
YSR734 shows potent in vitro activity as a covalent HDAC inhibitor with IC50 values of 110 nM, 154 nM, and 143 nM for HDAC1, HDAC2, and HDAC3, respectively. The compound can induce apoptosis in leukemia cells. YSR734 can also induce myoblast differentiation, making it useful for the study of Duchenne muscular dystrophy. |
| ln Vivo |
In vivo activity of YSR734 has been suggested based on its potent in vitro HDAC inhibitory activity and its ability to induce apoptosis in leukemia cells and myoblast differentiation. The compound is used in research applications for acute myeloid leukemia and Duchenne muscular dystrophy. However, detailed in vivo efficacy data have not been extensively reported in the available literature.
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| Enzyme Assay |
Non-cell-based enzyme assays for YSR734 typically involve measuring the inhibition of recombinant HDAC1, HDAC2, and HDAC3 activities using fluorogenic substrates. A standard protocol includes incubating purified HDAC enzyme with a fluorogenic substrate (such as Boc-Lys(Ac)-AMC) in assay buffer at 37°C. YSR734 is added at various concentrations (0.001–100 μM), and the release of fluorescent AMC is monitored over time. IC50 values are calculated from dose-response curves.
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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].
Cellular assays for YSR734 typically involve leukemia cell lines (e.g., acute myeloid leukemia cells) or myoblast cell lines. A representative protocol includes culturing cells in appropriate medium, treating with YSR734 at various concentrations (0.01–100 μM) for 24–72 hours, and assessing cell viability using MTT or CellTiter-Glo assays. Apoptosis is measured by flow cytometry using Annexin V staining. Myoblast differentiation is assessed by measuring myotube formation and expression of differentiation markers. |
| Animal Protocol |
In vivo animal studies with YSR734 have not been extensively reported in the available literature. If conducted, a typical protocol would involve xenograft mouse models of acute myeloid leukemia or mouse models of Duchenne muscular dystrophy. Administration of YSR734 via oral gavage or intraperitoneal injection would be followed by assessment of tumor growth, muscle function, and histopathological analysis.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of YSR734 have not been extensively reported in the available literature. The compound has a molecular weight of 598.54 g/mol and is soluble in DMSO at 100 mg/mL. In vivo formulation: 10% DMSO >> 90% corn oil (solubility: ≥ 5 mg/mL). The compound is stored as a powder at -20°C for up to 3 years and in solvent at -80°C for 6 months.
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| Toxicity/Toxicokinetics |
As a research compound, YSR734 is not intended for human therapeutic use, and comprehensive toxicological data are limited to preclinical studies. Standard safety assessments would include cytotoxicity screening, hERG channel inhibition testing, and preliminary toxicology studies in animal models to determine maximum tolerated dose and identify potential target organs of toxicity. The compound is for research use only.
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| References | |
| Additional Infomation |
Histone deacetylases (HDACs) are potent epigenetic modifiers of both histone and non-histone proteins by catalyzing the deacetylation of ε-N-acetylsine. Dysregulation of these zinc (Zn2+)-dependent hydrolases is closely associated with a variety of diseases, particularly cancer. Clinically, the recurring dose-limiting toxicities of first-generation HDAC inhibitors have prompted a shift towards developing safer, subtype-specific molecules. Given the broad role of HDACs in various aggressive diseases, novel approaches to targeting these enzymes remain necessary. This article reports the discovery of YSR734, a first-in-class covalent HDAC inhibitor composed of a 2-aminobenzoimide zinc ion chelate and a pentafluorobenzenesulfonamide electrophilic agent. This class I selective proof-of-concept compound, modified with the HDAC2Cys274 (catalytic domain), exhibits nanomolar potency against HDAC1–3, submicromolar activity in MV4–11 cells, and limited cytotoxicity against MRC-9 fibroblasts. In C2C12 myoblasts, YSR734 activates the muscle-specific biomarker myopoietin/Cav3, thereby effectively inducing their differentiation into myotubes (which can be applied to Duchenne muscular dystrophy). Current research focuses on improving its in vivo ADME properties in order to develop a preclinical covalent HDAC inhibitor. [1]
YSR734 (Compound 21) is a first-in-class covalent HDAC inhibitor with a 2-aminobenzanilide Zn2+ chelate and a pentafluorobenzene sulfonamide electrophile. The compound shows potent activity against HDAC1, HDAC2, and HDAC3 with IC50 values of 110 nM, 154 nM, and 143 nM, respectively. YSR734 induces apoptosis in leukemia cells and induces myoblast differentiation, and is used in the study of Duchenne muscular dystrophy. The compound is referenced in the primary literature (Journal of Medicinal Chemistry, 2023). |
| 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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| SMILES |
C1CN(CCC1OC(=O)NCC2=CC=C(C=C2)C(=O)NC3=CC=CC=C3N)S(=O)(=O)C4=C(C(=C(C(=C4F)F)F)F)F
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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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