WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406285
Description: TMP269 is a highly potent, selective and cell-permeable class IIa HDAC inhibitor with IC50 of 126 nM, 80 nM, 36 nM and 19 nM for HDAC4, HDAC5, HDAC7 and HDAC9 respectively.
MedKoo Cat#: 406285
Chemical Formula: C25H21F3N4O3S
Exact Mass: 514.12865
Molecular Weight: 514.52
Elemental Analysis: C, 58.36; H, 4.11; F, 11.08; N, 10.89; O, 9.33; S, 6.23
Synonym: TMP269; TMP 269; TMP-269
IUPAC/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 Key: HORXBWNTEDOVKN-UHFFFAOYSA-N
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
Appearance: white to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||TMP269 is a potent, selective class IIa HDAC inhibitor with IC50 of 157 nM, 97 nM, 43 nM and 23 nM for HDAC4, HDAC5, HDAC7 and HDAC9, respectively.|
|In vitro activity:||Exposure of IEC-18 cells to increasing concentrations of TMP269 potently inhibited [3H]thymidine incorporation induced by ANG II in these cells. Half-maximal inhibitory effect was elicited at ∼1.5 μM (Fig. 6B). Confluent and serum-starved cultures of IEC-18 cells were stimulated with ANG II in the absence or presence of 4 μM TMP269. Cells that traversed the cell cycle were accumulated in the G2/M phase by addition of colchicine. As shown in Fig. 6C, stimulation of IEC-18 cells with ANG II induced a striking shift from the G0/G1 to the G2/M phase, an effect completely prevented by exposure to TMP269. Furthermore, the inhibitors of class IIa HDACs also abolished the increase in cell number induced by ANG II in IEC-18 cells (Fig. 6D). Collectively, the results demonstrate, for the first time, that pharmacological inhibition of class IIa HDAC activity completely prevented GPCR/PKD1-induced progression of the cell cycle, DNA synthesis, and proliferation in IEC-18 cells. Reference: Am J Physiol Cell Physiol. 2014 May 15;306(10):C961-71. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24647541/|
|In vivo activity:||Male Sprague-Dawley rats were randomly divided into sham, ischemia/reperfusion, and 1, 4, 10 and 16 mg/kg TMP269 groups. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. TMP269 was intraperitoneally administered at different doses 0.5 hours before ischemia induction. Western blot assay and immunohistochemistry were used to detect effects of TMP269 on histone 2 acetylation. The results showed that the level of histone 2 acetylation was increased 24 hours after TMP269 injection. 2,3,5-Triphenyltetrazolium chloride staining was utilized to examine effect of TMP269 on infarct volume. The results found that different doses of TMP269 could reduce the infarct volume. Western blot assay, immunohistochemistry and Evans blue staining were employed to measure the effect of TMP269 on blood-brain barrier. The results showed that TMP269 counteracted the abnormal endothelial cell permeability changes caused by cerebral ischemia/reperfusion. Western blot assay and immunohistochemistry were used to determine the effect of TMP269 on tissue kallikrein. The results found that TMP269 up-regulated the expression of tissue kallikrein. Western blot assay further determined the optimal concentration to be 4 mg/kg. In conclusion, TMP269 plays a neuroprotective role by up-regulating the level of histone 2 acetylation, alleviating endothelial cell injury after cerebral ischemia/reperfusion, and up-regulating the expression of tissue kallikrein. Reference: Neural Regen Res. 2020 Feb;15(2):277-284. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31552900/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 514.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||1. Sinnett-Smith J, Ni Y, Wang J, Ming M, Young SH, Rozengurt E. Protein kinase D1 mediates class IIa histone deacetylase phosphorylation and nuclear extrusion in intestinal epithelial cells: role in mitogenic signaling. Am J Physiol Cell Physiol. 2014 May 15;306(10):C961-71. doi: 10.1152/ajpcell.00048.2014. Epub 2014 Mar 19. PMID: 24647541; PMCID: PMC4024715. 2. Kikuchi S, Suzuki R, Ohguchi H, Yoshida Y, Lu D, Cottini F, Jakubikova J, Bianchi G, Harada T, Gorgun G, Tai YT, Richardson PG, Hideshima T, Anderson KC. Class IIa HDAC inhibition enhances ER stress-mediated cell death in multiple myeloma. Leukemia. 2015 Sep;29(9):1918-27. doi: 10.1038/leu.2015.83. Epub 2015 Mar 24. PMID: 25801913.|
|In vivo protocol:||1. Su L, Liang D, Kuang SY, Dong Q, Han X, Wang Z. Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury. Neural Regen Res. 2020 Feb;15(2):277-284. doi: 10.4103/1673-5374.265562. PMID: 31552900; PMCID: PMC6905324.|
1. Lobera M, et al. Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. (2013) Nat Chem Biol. 9(5):319-25.