WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407429
CAS#: 1310693-92-5 (HCl)
Description: Tubastatin A is a potent and selective HDAC6 inhibitor. Tubastatin A demonstrates 1093-fold selectivity over HDAC1 (IC50 values of 15 nM for HDAC6 vs 16.4 µM for HDAC1). Tubastatin A was substantially more selective than the known HDAC6 inhibitor Tubacin at all isozymes except HDAC8. Tubastatin A is a potent HDAC6 inhibitor with an IC50 value of 15 nM. Comparatively, it demonstrates over 1,000-fold selectivity against all other HDAC isoforms (IC50 >16 μM), excluding HDAC8 (IC50= 0.9 μM). Tubastatin A induces α-tubulin hyperacetylation at 2.5 μM in primary cortical neuron cultures. In a model of oxidative stress induced by glutathione depletion, tubastatin A displays dose-dependent neuronal protection of primary cortical neuron cultures at 5-10 μM.
Hodoodo Cat#: H407429
Name: Tubastatin A HCl
CAS#: 1310693-92-5 (HCl)
Chemical Formula: C20H22ClN3O
Exact Mass: 0.00
Molecular Weight: 371.865
Elemental Analysis: C, 64.60; H, 5.96; Cl, 9.53; N, 11.30; O, 8.60
Related CAS #: 1310693-92-5 (HCl) 1252003-15-8 (free base) 1239034-70-8 (TFA)
Synonym: Tubastatin A HCl; Tubastatin A hydrochloride.
IUPAC/Chemical Name: N-hydroxy-4-((2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzamide hydrochloride
InChi Key: LJTSJTWIMOGKRJ-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H21N3O2.ClH/c1-22-11-10-19-17(13-22)16-4-2-3-5-18(16)23(19)12-14-6-8-15(9-7-14)20(24)21-25;/h2-9,25H,10-13H2,1H3,(H,21,24);1H
SMILES Code: O=C(NO)C1=CC=C(CN2C3=C(CN(C)CC3)C4=C2C=CC=C4)C=C1.[H]Cl
Appearance: 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
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:
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The following data is based on the product molecular weight 371.87 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: | |
| In vivo protocol: |
1: Wang M, Gao M, Miller KD, Sledge GW, Zheng QH. [11C]GSK2126458 and [18F]GSK2126458, the first radiosynthesis of new potential PET agents for imaging of PI3K and mTOR in cancers. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1569-74. doi: 10.1016/j.bmcl.2011.12.136. Epub 2012 Jan 10. PubMed PMID: 22297110.
2: Liu T, Sun Q, Li Q, Yang H, Zhang Y, Wang R, Lin X, Xiao D, Yuan Y, Chen L, Wang W. Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. Mol Cancer Ther. 2015 Feb;14(2):429-39. doi: 10.1158/1535-7163.MCT-14-0548. Epub 2014 Dec 12. PubMed PMID: 25504751.
3: Albawardi A, Al Ayyan M, Al Bashir M, Souid AK, Almarzooqi S. In vitro assessment of antitumor activities of the PI3K/mTOR inhibitor GSK2126458. Cancer Cell Int. 2014 Sep 24;14(1):90. doi: 10.1186/s12935-014-0090-z. eCollection 2014. PubMed PMID: 25298748; PubMed Central PMCID: PMC4189195.
4: Leung E, Kim JE, Rewcastle GW, Finlay GJ, Baguley BC. Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells. Cancer Biol Ther. 2011 Jun 1;11(11):938-46. Epub 2011 Jun 1. PubMed PMID: 21464613; PubMed Central PMCID: PMC3127046.
5: Dolman ME, Westerhout EM, Hamdi M, Schellens JH, Beijnen JH, Sparidans RW. Liquid chromatography-tandem mass spectrometric assay for the PI3K/mTOR inhibitor GSK2126458 in mouse plasma and tumor homogenate. J Pharm Biomed Anal. 2015 Mar 25;107:403-8. doi: 10.1016/j.jpba.2015.01.026. Epub 2015 Jan 19. PubMed PMID: 25659532.
6: Vaidhyanathan S, Wilken-Resman B, Ma DJ, Parrish KE, Mittapalli RK, Carlson BL, Sarkaria JN, Elmquist WF. Factors Influencing the Central Nervous System Distribution of a Novel Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GSK2126458: Implications for Overcoming Resistance with Combination Therapy for Melanoma Brain Metastases. J Pharmacol Exp Ther. 2016 Feb;356(2):251-9. doi: 10.1124/jpet.115.229393. Epub 2015 Nov 24. PubMed PMID: 26604245; PubMed Central PMCID: PMC4727156.
7: Park H, Kim Y, Sul JW, Jeong IG, Yi HJ, Ahn JB, Kang JS, Yun J, Hwang JJ, Kim CS. Synergistic anticancer efficacy of MEK inhibition and dual PI3K/mTOR inhibition in castration-resistant prostate cancer. Prostate. 2015 Nov;75(15):1747-59. doi: 10.1002/pros.23057. Epub 2015 Aug 7. PubMed PMID: 26250606.
8: Knight SD, Adams ND, Burgess JL, Chaudhari AM, Darcy MG, Donatelli CA, Luengo JI, Newlander KA, Parrish CA, Ridgers LH, Sarpong MA, Schmidt SJ, Van Aller GS, Carson JD, Diamond MA, Elkins PA, Gardiner CM, Garver E, Gilbert SA, Gontarek RR, Jackson JR, Kershner KL, Luo L, Raha K, Sherk CS, Sung CM, Sutton D, Tummino PJ, Wegrzyn RJ, Auger KR, Dhanak D. Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin. ACS Med Chem Lett. 2010 Jan 19;1(1):39-43. doi: 10.1021/ml900028r. eCollection 2010 Apr 8. PubMed PMID: 24900173; PubMed Central PMCID: PMC4007793.
9: Munster P, Aggarwal R, Hong D, Schellens JH, van der Noll R, Specht J, Witteveen PO, Werner TL, Dees EC, Bergsland E, Agarwal N, Kleha JF, Durante M, Adams L, Smith DA, Lampkin TA, Morris SR, Kurzrock R. First-in-Human Phase I Study of GSK2126458, an Oral Pan-Class I Phosphatidylinositol-3-Kinase Inhibitor, in Patients with Advanced Solid Tumor Malignancies. Clin Cancer Res. 2016 Apr 15;22(8):1932-9. doi: 10.1158/1078-0432.CCR-15-1665. Epub 2015 Nov 24. PubMed PMID: 26603258.
10: Mercer PF, Woodcock HV, Eley JD, Platé M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Blanchard AD, Marshall RP, Lukey PT, Chambers RC. Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF. Thorax. 2016 Aug;71(8):701-11. doi: 10.1136/thoraxjnl-2015-207429. Epub 2016 Apr 21. PubMed PMID: 27103349; PubMed Central PMCID: PMC4975851.
11: Grilley-Olson JE, Bedard PL, Fasolo A, Cornfeld M, Cartee L, Razak AR, Stayner LA, Wu Y, Greenwood R, Singh R, Lee CB, Bendell J, Burris HA, Del Conte G, Sessa C, Infante JR. A phase Ib dose-escalation study of the MEK inhibitor trametinib in combination with the PI3K/mTOR inhibitor GSK2126458 in patients with advanced solid tumors. Invest New Drugs. 2016 Dec;34(6):740-749. Epub 2016 Jul 23. PubMed PMID: 27450049.
12: Ma J, Sun Y, López FJ, Adamson P, Kurali E, Lashkari K. Blockage of PI3K/mTOR Pathways Inhibits Laser-Induced Choroidal Neovascularization and Improves Outcomes Relative to VEGF-A Suppression Alone. Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3138-44. doi: 10.1167/iovs.15-18795. PubMed PMID: 27304845.
13: Leung EY, Askarian-Amiri M, Finlay GJ, Rewcastle GW, Baguley BC. Potentiation of Growth Inhibitory Responses of the mTOR Inhibitor Everolimus by Dual mTORC1/2 Inhibitors in Cultured Breast Cancer Cell Lines. PLoS One. 2015 Jul 6;10(7):e0131400. doi: 10.1371/journal.pone.0131400. eCollection 2015. PubMed PMID: 26148118; PubMed Central PMCID: PMC4492962.
14: Kim HG, Tan L, Weisberg EL, Liu F, Canning P, Choi HG, Ezell SA, Wu H, Zhao Z, Wang J, Mandinova A, Griffin JD, Bullock AN, Liu Q, Lee SW, Gray NS. Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor. ACS Chem Biol. 2013 Oct 18;8(10):2145-50. doi: 10.1021/cb400430t. Epub 2013 Aug 13. Erratum in: ACS Chem Biol. 2014 Mar 21;9(3):840. PubMed PMID: 23899692; PubMed Central PMCID: PMC3800496.
15: Basu D, Salgado CM, Bauer BS, Johnson D, Rundell V, Nikiforova M, Khakoo Y, Gunwaldt LJ, Panigrahy A, Reyes-Múgica M. Nevospheres from neurocutaneous melanocytosis cells show reduced viability when treated with specific inhibitors of NRAS signaling pathway. Neuro Oncol. 2016 Apr;18(4):528-37. doi: 10.1093/neuonc/nov184. Epub 2015 Sep 9. PubMed PMID: 26354928; PubMed Central PMCID: PMC4799680.
16: Greger JG, Eastman SD, Zhang V, Bleam MR, Hughes AM, Smitheman KN, Dickerson SH, Laquerre SG, Liu L, Gilmer TM. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 2012 Apr;11(4):909-20. doi: 10.1158/1535-7163.MCT-11-0989. Epub 2012 Mar 2. PubMed PMID: 22389471.
17: Villanueva J, Infante JR, Krepler C, Reyes-Uribe P, Samanta M, Chen HY, Li B, Swoboda RK, Wilson M, Vultur A, Fukunaba-Kalabis M, Wubbenhorst B, Chen TY, Liu Q, Sproesser K, DeMarini DJ, Gilmer TM, Martin AM, Marmorstein R, Schultz DC, Speicher DW, Karakousis GC, Xu W, Amaravadi RK, Xu X, Schuchter LM, Herlyn M, Nathanson KL. Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma. Cell Rep. 2013 Sep 26;4(6):1090-9. doi: 10.1016/j.celrep.2013.08.023. Epub 2013 Sep 19. PubMed PMID: 24055054; PubMed Central PMCID: PMC3956616.
18: Leung EY, Kim JE, Askarian-Amiri M, Rewcastle GW, Finlay GJ, Baguley BC. Relationships between signaling pathway usage and sensitivity to a pathway inhibitor: examination of trametinib responses in cultured breast cancer lines. PLoS One. 2014 Aug 29;9(8):e105792. doi: 10.1371/journal.pone.0105792. eCollection 2014. PubMed PMID: 25170609; PubMed Central PMCID: PMC4149495.
19: Al-Hammadi S, Almarzooqi S, Albawardi A, Souid AK. Effects of molecularly targeted therapies on murine thymus: highly selective mTOR inhibitors induce reversible thymic involution. Exp Hematol Oncol. 2016 Jul 29;5:22. doi: 10.1186/s40164-016-0044-3. eCollection 2015. PubMed PMID: 27478685; PubMed Central PMCID: PMC4966723.
20: Song WY, Yang QL, Zhao WL, Jin HX, Yao GD, Peng ZF, Shi SL, Yang HY, Zhang XY, Sun YP. The effects of anticancer drugs TSA and GSK on spermatogenesis in male mice. Am J Transl Res. 2016 Jan 15;8(1):221-9. eCollection 2016. PubMed PMID: 27069555; PubMed Central PMCID: PMC4759431.
