| 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 |
| Targets |
HDAC6
TYA-018 targets HDAC6 (histone deacetylase 6), a class IIb histone deacetylase that primarily deacetylates non-histone proteins including α-tubulin, HSP90, and cortactin. HDAC6 is involved in various cellular processes including cell motility, protein aggregation, and immune responses. Inhibition of HDAC6 by TYA-018 leads to increased acetylation of α-tubulin and other substrates, promoting autophagy and reducing protein aggregation. The compound has an IC50 of 10 nM against HDAC6, demonstrating high potency and selectivity. |
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| ln Vitro |
TYA-018 is a potent and highly selective HDAC6 inhibitor with an IC50 of 10 nM. It inhibits tubulin acetylation (Ac-Tubulin) with an EC50 of 120 nM in cell-based assays in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The compound demonstrates high selectivity for HDAC6 over other HDAC isoforms, making it a valuable tool for studying HDAC6 biology. In vitro studies have shown its ability to modulate autophagy and reduce protein aggregation.
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| ln Vivo |
In BAG3cKO mice, TYA-018 (15 mg/kg, oral gavage, daily, for 8 weeks) decreases Nppb expression and avoids sarcomere degradation [1].
TYA-018 has demonstrated in vivo efficacy in mouse models. TYA-018 (15 mg/kg, oral gavage, daily for 8 weeks) prevents sarcomere damage and decreases Nppb expression in BAG3cKO mice. The compound can protect heart function in mice and enhances energetics by increasing expression of targets associated with fatty acid metabolism, protein metabolism, and oxidative phosphorylation. It has cardioprotective properties for the study of dilated heart disease and heart failure. |
| Enzyme Assay |
For HDAC6 enzyme inhibition assays, purified HDAC6 is incubated with a fluorogenic peptide substrate (e.g., Ac-Lys(Ac)-AMC) and TYA-018 at various concentrations. Deacetylase activity is measured by fluorescence increase upon cleavage of the deacetylated substrate by trypsin. IC50 values are calculated from dose-response curves. Selectivity profiling is conducted by screening the compound against a panel of HDAC isoforms to assess specificity for HDAC6 over other HDACs.
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| Cell Assay |
For cellular activity studies, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) or other relevant cell types are cultured in appropriate media. Cells are treated with TYA-018 at various concentrations for 24-72 hours. HDAC6 inhibition is assessed by measuring acetylation of α-tubulin (Ac-Tubulin) by Western blot using specific antibodies against acetylated tubulin. EC50 values are calculated from dose-response curves. Autophagy markers (LC3-II/LC3-I ratio, p62) are assessed by Western blot. Cell viability is assessed using MTT or CellTiter-Glo assays.
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| Animal Protocol |
Animal/Disease Models: BAG3cKO mice[1]
Doses: 15 mg/kg Route of Administration: po (oral gavage), daily, starting at 2 months old, for 8 weeks Experimental Results: Conferred cardioprotection in mice. Dramatically diminished Nppb expression to near WT. diminished fibrosis in BAG3cKO mice, although not Dramatically. partially restored protein expression of FLNC, PINK1, VDAC2, and p62 to amounts similar to WT mice. Dramatically diminished the percentage of cardiomyocytes with damaged and diminished sarcomeres in BAG3cKO mice. Dramatically diminished mitochondrial content to amounts similar to WT mice. For in vivo efficacy studies, BAG3cKO mice or other relevant mouse models are administered TYA-018 orally by gavage at various doses (e.g., 15 mg/kg daily). Treatment duration is typically 8 weeks. Cardiac function is assessed by echocardiography. Sarcomere damage is evaluated by histopathological analysis of heart tissues. Nppb expression (a marker of cardiac stress) is measured by qRT-PCR. Body weight is monitored for toxicity assessment. Pharmacokinetic studies are conducted to determine compound exposure in plasma and cardiac tissues. |
| ADME/Pharmacokinetics |
TYA-018 is an orally active compound with favorable pharmacokinetic properties. As a small molecule with molecular weight 434.81, it is expected to have good oral absorption and tissue penetration. The compound's oral bioavailability supports convenient dosing in preclinical studies. Detailed pharmacokinetic parameters such as half-life, Cmax, AUC, and protein binding are being characterized in preclinical studies. The compound is typically stored according to manufacturer recommendations.
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| Toxicity/Toxicokinetics |
TYA-018 is a research compound intended for laboratory use only and is not approved for human therapeutic use. As a potent and selective HDAC6 inhibitor, it has cardioprotective properties for the study of dilated heart disease and heart failure. The compound prevents sarcomere damage and decreases Nppb expression in mouse models. Standard laboratory safety precautions should be followed when handling this compound. Purity is >98% by HPLC.
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| References | |
| Additional Infomation |
TYA-018 is an orally active, potent, and highly selective HDAC6 inhibitor with molecular formula C15H13ClF2N4O3S2. It has an IC50 of 10 nM against HDAC6 and inhibits tubulin acetylation with an EC50 of 120 nM in iPSC-CMs. TYA-018 protects heart function in mice and enhances energetics by increasing fatty acid metabolism, protein metabolism, and oxidative phosphorylation targets. It is used in the study of dilated heart disease and heart failure. The compound is for research use only and has not been approved for clinical applications. Purity >98% by HPLC.
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| Molecular Formula |
C15H13CLF2N4O3S2
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| Molecular Weight |
434.87
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| Exact Mass |
434.008
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| CAS # |
2653254-31-8
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| PubChem CID |
156525534
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| Appearance |
White to yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
27
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| Complexity |
598
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N(C1C=CC=C(C=1)Cl)(S(=O)(=O)CC)CC1=NC=C(C2=NN=C(O2)C(F)F)S1
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| InChi Key |
DAMJZODYLBMFHQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13ClF2N4O3S2/c1-2-27(23,24)22(10-5-3-4-9(16)6-10)8-12-19-7-11(26-12)14-20-21-15(25-14)13(17)18/h3-7,13H,2,8H2,1H3
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| Chemical Name |
N-(3-chlorophenyl)-N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-1,3-thiazol-2-yl]methyl]ethanesulfonamide
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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 (229.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.75 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
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 (5.75 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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: 2.5 mg/mL (5.75 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2995 mL | 11.4977 mL | 22.9954 mL | |
| 5 mM | 0.4599 mL | 2.2995 mL | 4.5991 mL | |
| 10 mM | 0.2300 mL | 1.1498 mL | 2.2995 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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