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    InvivoChem Cat #: V0269
    CAS #: 1314890-29-3Purity ≥98%

    Description: TMP269 is a novel, potent, selective inhibitor of class IIa HDAC(4/5/7/9) with potential anticancer activity. It inhibits HDAC(4/5/7/9) with IC50 of 157 nM, 97 nM, 43 nM and 23 nM, respectively. 

    References: Nat Chem Biol. 2013 May;9(5):319-25; Am J Physiol Cell Physiol. 2014 May 15;306(10):C961-71.

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    Molecular Weight (MW)514.52
    CAS No.1314890-29-3
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 100 mg/mL (194.4 mM)
    Water: <1 mg/mL
    Ethanol: 2 mg/mL (3.88 mM)
    Other info

    Chemical Name: N-((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamide


    InChi Code: InChI=1S/C25H21F3N4O3S/c26-25(27,28)22-31-20(32-35-22)17-7-4-8-18(13-17)21(33)29-15-24(9-11-34-12-10-24)23-30-19(14-36-23)16-5-2-1-3-6-16/h1-8,13-14H,9-12,15H2,(H,29,33)

    SMILES Code: O=C(NCC1(C2=NC(C3=CC=CC=C3)=CS2)CCOCC1)C4=CC=CC(C5=NOC(C(F)(F)F)=N5)=C4

    SynonymsTMP269; TMP-269; TMP 269;

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    In Vitro

    In vitro activity: TMP269 has no impact on the mitochondrial activity and/or the viability of human CD4+ T cells at 10 μM, and may be used as tools to identify the endogenous substrates of the class IIa HDAC enzymes. In IEC-18 intestinal epithelial cells, TMP269 prevents cell cycle progression, DNA synthesis, and proliferation induced in response to G protein-coupled receptor/PKD1 activation

    Kinase Assay: Dose-response studies are done with ten concentrations in a threefold dilution series from a maximum final compound concentration of 100 μM in the reaction mixture and are conducted at Reaction Biology Corp. All assays are based on the same principle as the HDAC9 assay described above: the deacetylation of acetylated or trifluoroacetylated lysine residues on fluorogenic peptide substrates by HDAC. HDAC1, HDAC2, HDAC3, HDAC6, HDAC10 and HDAC11 used a substrate based on residues 379-382 of p53 (Arg-His-Lys-Lys(Ac)). For HDAC8, the diacetylated peptide substrate, based on residues 379–382 of p53 (Arg-His-Lys(Ac)-Lys(Ac)), is used. HDAC4, HDAC5, HDAC7 and HDAC9 assays used the class IIa HDAC–specific fluorogenic substrate (Boc-Lys(trifluoroacetyl)-AMC). All reactions are done with 50 μM HDAC substrate in assay buffer (50 mM Tris-HCl, pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mg/mL BSA) containing 1% DMSO final concentration; incubated for 2 h at 30 °C; and developed with trichostatin A and trypsin. 

    Cell Assay: Human CD4+ T cells are isolated from whole blood via negative selection according to manufacturer's instructions (RosetteSep Human CD4+ T cell enrichment kit), re-suspended in T-cell culture medium (10% FBS, 2 mM L-glutamine, 1 mM pyruvate, 10 mM HEPES, 10 U/10 mg penicillin/streptomycin, 0.5% DMSO in RPMI) and plated at 50,000 cells/well with IL-2 (10 BRMP units/mL) and 100,000 human T-expander Dynabeads for 72 h. Determination of mitochondrial function or cell viability is done according to manufacturer’s instructions (Cell Proliferation Assay Kit I (MTT)) and is represented as a percent of control (no inhibitor) wells.

    In VivoN/A
    Animal modelN/A
    Formulation & DosageN/A

    Nat Chem Biol. 2013 May;9(5):319-25; Am J Physiol Cell Physiol. 2014 May 15;306(10):C961-71.

    These protocols are for reference only. InvivoChem does not independently validate these methods.

    Class IIa HDAC catalytic domain activity is necessary for mitogenic signaling induced by ANG II in intestinal epithelial cells. Am J Physiol Cell Physiol. 2014 May 15;306(10):C961-71. 
    Class IIa HDAC inhibition by MC1568 or TMP269 does not prevent PKD1 activation, HDAC4 and HDAC5 phosphorylation, and HDAC5 nuclear extrusion in IEC-18 cells stimulated with ANG II. Am J Physiol Cell Physiol. 2014 May 15;306(10):C961-71. 


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