| Identification | Back Directory | [Name]
TAS-116 | [CAS]
1260533-36-5 | [Synonyms]
TAS-116
TAS 116;TAS116
Des-iPr-TAS-116
3-ethyl-4-{3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzamide
Benzamide, 3-ethyl-4-[3-(1-methylethyl)-4-[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-1H-pyrazolo[3,4-b]pyridin-1-yl]- | [Molecular Formula]
C25H26N8O | [MDL Number]
MFCD28502196 | [MOL File]
1260533-36-5.mol | [Molecular Weight]
454.53 |
| Chemical Properties | Back Directory | [Boiling point ]
661.7±55.0 °C(Predicted) | [density ]
1.36±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: soluble | [form ]
A solid | [pka]
15.43±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Pimitespib (TAS-116) is an oral bioavailable, ATP-competitive, highly specific HSP90α/HSP90β inhibitor (Kis of 34.7 nM and 21.3 nM, respectively) without inhibiting other HSP90 family proteins such as GRP94[1]. Pimitespib demonstrates less ocular toxicity[2]. | [Biological Activity]
TAS-116 is a novel small molecule inhibitor of HSP90 with Ki values of 34.7 nmol/L and 21.3 nmol/L for HSP90α and HSP90β, respectively. It does not inhibit other ATPases such as HSP70 (IC50 >200 μmol/L). | [in vitro]
TAS-116 is a selective inhibitor of HSP90α and HSP90β in the cytoplasm, but has no inhibitory effect on endoplasmic reticulum GRP94 or mitochondrial TRAP1. Treatment of HCT116 cells with 0.3 μM of TAS-1116 for 8 hours resulted in a decrease in DDR1 levels and induction of HSP70. | [in vivo]
In a mouse model with human xenograft tumors, oral administration of TAS-116 induced tumor shrinkage accompanied by depletion of HSP90. In a rat model, TAS-116 was more distributed in subcutaneously xenografted NCI-H1975 non-small cell lung cancer tumors than in the retina. TAS-116 was also active in orthotopically transplanted NCI-H1975 lung tumors. | [target]
| Target | Value | HSP90β
(Cell-free assay) | 21.3 nM(Ki) | HSP90α
(Cell-free assay ) | 34.7 nM(Ki) |
| [IC 50]
HSP90α: 34.7 nM (Ki); HSP90β: 21.3 nM (Ki) | [storage]
Store at -20°C | [References]
[1] Ohkubo S, et al. TAS-116, a highly selective inhibitor of heat shock protein 90α and β, demonstrates potent antitumor activity and minimal ocular toxicity in preclinical models. Mol Cancer Ther. 2015 Jan;14(1):14-22. DOI:10.1158/1535-7163.MCT-14-0219
[2] Suzuki R, et al. Anti-tumor activities of selective HSP90α/β inhibitor, TAS-116, in combination with PS-341 in multiple myeloma. Leukemia. 2015 Feb;29(2):510-4. DOI:10.1038/leu.2014.300
[3] Utsugi T. New challenges and inspired answers for anticancer drug discovery and development. Jpn J Clin Oncol. 2013 Oct;43(10):945-53. DOI:10.1093/jjco/hyt131 |
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NCE Biomedical Co.,Ltd.
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SPIRO PHARMA
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www.spiropharma.com.cn |
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