TMP269 | CAS#1314890-29-3 | HDAC inhibitor

MedKoo Cat#: 406285 | Name: TMP269

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

TMP269

CAS#1314890-29-3

Theoretical Analysis

MedKoo Cat#: 406285

Name: TMP269

CAS#: 1314890-29-3

Chemical Formula: C25H21F3N4O3S

Exact Mass: 514.1287

Molecular Weight: 514.52

Elemental Analysis: C, 58.36; H, 4.11; F, 11.08; N, 10.89; O, 9.33; S, 6.23

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to ship

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Related CAS #

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC51216

View CoA: current batch, Lot#BBC40929

QC Data

View QC data: current batch, Lot#TCZ51216

View QC data: current batch, Lot#BBC40929

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMF	25.0	48.60
	DMSO	10.0	19.40
	Ethanol	0.3	0.50

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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

Formulation protocol:

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: Beter M, Pulkkinen HH, Örd T, Sormunen A, Kilpeläinen L, Dunford JE, Kaikkonen MU, Aavik E, Laham-Karam N, Oppermann U, Laakkonen JP, Ylä-Herttuala S. Epigenetic drug screening identifies enzyme inhibitors A-196 and TMP-269 as novel regulators of sprouting angiogenesis. Sci Rep. 2025 Jan 10;15(1):1628. doi: 10.1038/s41598-024-84603-w. PMID: 39794417; PMCID: PMC11724134. 2: Miyazawa Y, Furugen A, Aoyagi R, Kosugi H, Nishimura A, Umazume T, Narumi K, Kobayashi M. Alteration in folate carrier expression via histone deacetylase inhibition in BeWo human placental choriocarcinoma cells. Toxicol In Vitro. 2024 Dec;101:105934. doi: 10.1016/j.tiv.2024.105934. Epub 2024 Sep 3. PMID: 39237058. 3: Meng Y, Xiao L, Liu R, Du J, Liu N, Yu J, Li Y, Lu G. Antidepressant effect and mechanism of TMP269 on stress-induced depressive-like behavior in mice. Biochem Pharmacol. 2024 Jul;225:116320. doi: 10.1016/j.bcp.2024.116320. Epub 2024 May 25. PMID: 38801927. 4: Yin J, Wang S, Ren S, Liang Z, Ge J, Sun Y, Yin X, Wang X. TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro. Front Microbiol. 2023 Dec 1;14:1284439. doi: 10.3389/fmicb.2023.1284439. PMID: 38107853; PMCID: PMC10722228. 5: Li XY, Yu JT, Dong YH, Shen XY, Hou R, Xie MM, Wei J, Hu XW, Dong ZH, Shan RR, Jin J, Shao W, Meng XM. Protein acetylation and related potential therapeutic strategies in kidney disease. Pharmacol Res. 2023 Nov;197:106950. doi: 10.1016/j.phrs.2023.106950. Epub 2023 Oct 17. PMID: 37820854. 6: Urwanisch L, Unger MS, Sieberer H, Dang HH, Neuper T, Regl C, Vetter J, Schaller S, Winkler SM, Kerschbamer E, Weichenberger CX, Krenn PW, Luciano M, Pleyer L, Greil R, Huber CG, Aberger F, Horejs-Hoeck J. The Class IIA Histone Deacetylase (HDAC) Inhibitor TMP269 Downregulates Ribosomal Proteins and Has Anti-Proliferative and Pro-Apoptotic Effects on AML Cells. Cancers (Basel). 2023 Feb 7;15(4):1039. doi: 10.3390/cancers15041039. PMID: 36831382; PMCID: PMC9953883. 7: Ito R, Miyanishi K, Kubo T, Hamaguchi K, Osuga T, Tanaka S, Ohnuma H, Murase K, Takada K, Nagayama M, Kimura Y, Mizuguchi T, Takemasa I, Kato J. Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma. Hepatol Int. 2023 Jun;17(3):735-744. doi: 10.1007/s12072-023-10484-2. Epub 2023 Feb 4. PMID: 36738397. 8: Qin Y, Imobersteg S, Frank S, Blanc A, Chiorazzo T, Berger P, Schibli R, Béhé MP, Grzmil M. Signaling Network Response to α-Particle-Targeted Therapy with the 225Ac-Labeled Minigastrin Analog 225Ac-PP-F11N Reveals the Radiosensitizing Potential of Histone Deacetylase Inhibitors. J Nucl Med. 2023 Jun;64(6):873-879. doi: 10.2967/jnumed.122.264597. Epub 2023 Feb 2. PMID: 36732057; PMCID: PMC10241010. 9: Bollmann LM, Skerhut AJ, Asfaha Y, Horstick N, Hanenberg H, Hamacher A, Kurz T, Kassack MU. The Novel Class IIa Selective Histone Deacetylase Inhibitor YAK540 Is Synergistic with Bortezomib in Leukemia Cell Lines. Int J Mol Sci. 2022 Nov 2;23(21):13398. doi: 10.3390/ijms232113398. PMID: 36362189; PMCID: PMC9656955. 10: Li J, Yu C, Shen F, Cui B, Liu N, Zhuang S. Class IIa histone deacetylase inhibition ameliorates acute kidney injury by suppressing renal tubular cell apoptosis and enhancing autophagy and proliferation. Front Pharmacol. 2022 Jul 22;13:946192. doi: 10.3389/fphar.2022.946192. PMID: 35935816; PMCID: PMC9354984. 11: Feng Y, Ma Z, Pan M, Xu L, Feng J, Zhang Y, Shao C, Guo K, Duan H, Zhang Y, Zhang Y, Zhang J, Lu D, Ren X, Han J, Li X, Yan X. WNT5A promotes the metastasis of esophageal squamous cell carcinoma by activating the HDAC7/SNAIL signaling pathway. Cell Death Dis. 2022 May 20;13(5):480. doi: 10.1038/s41419-022-04901-x. PMID: 35595735; PMCID: PMC9122958. 12: OuYang C, Shu G, Liu J, Deng S, Lu P, Li Y, Gan Y, Xie B, Liu J, Yin G. HDAC5, negatively regulated by miR-148a-3p, promotes colon cancer cell migration. Cancer Sci. 2022 Aug;113(8):2560-2574. doi: 10.1111/cas.15399. Epub 2022 Jun 5. Erratum in: Cancer Sci. 2024 Apr;115(4):1361. doi: 10.1111/cas.16125. PMID: 35574707; PMCID: PMC9357626. 13: Zhang Y, Lei Y, Honarpisheh M, Kemter E, Wolf E, Seissler J. Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells. Cells. 2021 Nov 19;10(11):3249. doi: 10.3390/cells10113249. PMID: 34831471; PMCID: PMC8621544. 14: Bai L, Kee HJ, Choi SY, Seok YM, Kim GR, Kee SJ, Kook H, Jeong MH. HDAC5 inhibition reduces angiotensin II-induced vascular contraction, hypertrophy, and oxidative stress in a mouse model. Biomed Pharmacother. 2021 Feb;134:111162. doi: 10.1016/j.biopha.2020.111162. Epub 2020 Dec 25. PMID: 33360932. 15: Kovacs-Kasa A, Kovacs L, Cherian-Shaw M, Patel V, Meadows ML, Fulton DJ, Su Y, Verin AD. Inhibition of Class IIa HDACs improves endothelial barrier function in endotoxin-induced acute lung injury. J Cell Physiol. 2021 Apr;236(4):2893-2905. doi: 10.1002/jcp.30053. Epub 2020 Sep 22. PMID: 32959895; PMCID: PMC9946131. 16: Elmezayen AD, Yelekçi K. Homology modeling and in silico design of novel and potential dual-acting inhibitors of human histone deacetylases HDAC5 and HDAC9 isozymes. J Biomol Struct Dyn. 2021 Oct;39(17):6396-6414. doi: 10.1080/07391102.2020.1798812. Epub 2020 Jul 27. PMID: 32715940. 17: Usami M, Kikuchi S, Takada K, Ono M, Sugama Y, Arihara Y, Hayasaka N, Nakamura H, Ikeda Y, Hirakawa M, Yoshida M, Miyanishi K, Kobune M, Kato J. FOXO3a Activation by HDAC Class IIa Inhibition Induces Cell Cycle Arrest in Pancreatic Cancer Cells. Pancreas. 2020 Jan;49(1):135-142. doi: 10.1097/MPA.0000000000001462. PMID: 31856089. 18: 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. 19: Hu T, Schreiter FC, Bagchi RA, Tatman PD, Hannink M, McKinsey TA. HDAC5 catalytic activity suppresses cardiomyocyte oxidative stress and NRF2 target gene expression. J Biol Chem. 2019 May 24;294(21):8640-8652. doi: 10.1074/jbc.RA118.007006. Epub 2019 Apr 8. PMID: 30962285; PMCID: PMC6544848. 20: Schang G, Toufaily C, Bernard DJ. HDAC inhibitors impair Fshb subunit expression in murine gonadotrope cells. J Mol Endocrinol. 2019 Feb 1;62(2):67-78. doi: 10.1530/JME-18-0145. PMID: 30481159.