TMP269
Modify Date: 2024-01-02 21:28:33
TMP269 structure
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Common Name | TMP269 | ||
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| CAS Number | 1314890-29-3 | Molecular Weight | 514.519 | |
| Density | 1.3±0.1 g/cm3 | Boiling Point | N/A | |
| Molecular Formula | C25H21F3N4O3S | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of TMP269TMP269 is a novel and selective class IIa histone deacetylase (HDAC) inhibitor with IC50s of 157 nM, 97 nM, 43 nM and 23 nM for HDAC4, HDAC5, HDAC7 and HDAC9, respectively. |
| Name | N-{[4-(4-Phenyl-1,3-thiazol-2-yl)tetrahydro-2H-pyran-4-yl]methyl} -3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide |
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| Synonym | More Synonyms |
| Description | TMP269 is a novel and selective class IIa histone deacetylase (HDAC) inhibitor with IC50s of 157 nM, 97 nM, 43 nM and 23 nM for HDAC4, HDAC5, HDAC7 and HDAC9, respectively. |
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| Related Catalog | |
| Target |
HDAC9:23 nM (IC50) HDAC7:43 nM (IC50) HDAC5:97 nM (IC50) HDAC4:157 nM (IC50) HDAC8:42000 nM (IC50) HDAC6:82000 nM (IC50) |
| In Vitro | 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[1]. 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[2]. As with HDAC4 knockdown, TMP269 significantly enhances cytotoxicity induced by CFZ in MM cell lines, upregulating ATF4 and CHOP and inducing apoptosis. TMP269 does not hyperacetylate histone H3K9 or α-tubulin in MM cell lines, confirming that it has no inhibitory effects on class I or IIb HDACs. In a dosedependent manner, TPM269-induced cytotoxicity is associated with cleavage of caspase-8, -9, -3 and PARP, consistent with apoptosis[3]. |
| 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. 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. |
| References |
| Density | 1.3±0.1 g/cm3 |
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| Molecular Formula | C25H21F3N4O3S |
| Molecular Weight | 514.519 |
| Exact Mass | 514.128662 |
| PSA | 121.87000 |
| LogP | 5.81 |
| Appearance of Characters | white solid |
| Index of Refraction | 1.574 |
| Storage condition | -20℃ |
| N-{[4-(4-Phenyl-1,3-thiazol-2-yl)tetrahydro-2H-pyran-4-yl]methyl}-3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide |
| Benzamide, N-[[tetrahydro-4-(4-phenyl-2-thiazolyl)-2H-pyran-4-yl]methyl]-3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]- |
| TMP269 |