TAS-116

Product Name: TAS-116
CAS No.: 1260533-36-5
Chemical Name: TAS-116
Synonyms: TAS-116;Pimitespib;TAS 116;TAS116;Des-iPr-TAS-116;Pimitespib (TAS-116);Pimitespib, 10 mM in DMSO;Pimitespib (TAS-116) ，S7716;inhibit,HSP,TAS 116,TAS116,Pimitespib,Heat shock proteins,Inhibitor;3-Ethyl-4-[4-[4-(1-methylpyrazol-4-yl)imidazol-1-yl]-3-propan-2-ylpyrazolo[3,4-b]pyridin-1-yl]benzamide;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
CBNumber: CB22716365
Molecular Formula: C25H26N8O
Formula Weight: 454.53
MOL File: 1260533-36-5.mol

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TAS-116 Property

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

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Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

ChemScene

Product number: CS-0009135
Product name: TAS-116
Purity: 98.96%
Packaging: 5mg
Price: $85
Updated: 2021/12/16

American Custom Chemicals Corporation

Product number: INB0004535
Product name: TAS-116
Purity: 95.00%
Packaging: 5MG
Price: $503.05
Updated: 2021/12/16

ChemScene

Product number: CS-0009135
Product name: TAS-116
Purity: 98.96%
Packaging: 50mg
Price: $530
Updated: 2021/12/16

ChemScene

Product number: CS-0009135
Product name: TAS-116
Purity: 98.96%
Packaging: 100mg
Price: $940
Updated: 2021/12/16

ChemScene

Product number: CS-0009135
Product name: TAS-116
Purity: 98.96%
Packaging: 10mg
Price: $1450
Updated: 2021/12/16

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TAS-116 Chemical Properties,Usage,Production

Description

TAS-116 (Chinese name: Pimitespib) is an oral heat shock protein 90 (HSP90) α and β subtype selective inhibitor developed by Taiho Pharmaceutical. HSP90 is a molecular chaperone protein that plays a key role in the stability and function of a variety of tumor growth-related proteins. Pimitespib inhibits the activity of HSP90, leading to the degradation of these tumor growth-related proteins, thereby inhibiting the growth and survival of tumor cells.

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).

Synthesis

First, pyridine 30.1 was reacted with LDA (dimethyl lithium) to be lithiated at the 3rd position via a halogen dance. The resulting metallated intermediate 30.2 was then quenched with isobutyric anhydride to form pyridine 30.3. Next, nucleophilic substitution reaction (SNAr) with hydrazine hydrate and cyclization gave pyrazolopyridine 30.4 in 24% overall yield from pyridine 30.1. The free nitrogen atom was introduced with a PMB protecting group by reaction with sodium hydride and p-methoxybenzyl chloride to give intermediate 30.5. This intermediate was reacted with 30.8 synthesized by Suzuki coupling via a copper-mediated coupling reaction followed by benzyl deprotection to give 30.9. The PMB protecting group was then removed using trifluoroacetic acid to give 30.9. The final fragment of Pimitespib was introduced by substitution reaction with 30.9 and 30.10. Finally, the nitrile 30.11 was hydrolyzed to the amide using sodium hydroxide and hydrogen peroxide to afford TAS-116 (30).

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)

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

TAS-116 Preparation Products And Raw materials

Raw materials

Preparation Products

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TAS-116 Suppliers

CHINA 81 United States 4 Global 85

NCE Biomedical Co.,Ltd.

Tel: 4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988
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Shanghai Macklin Biochemical Co.,Ltd.

Tel: 15221275939
Fax: 021-50706099
Email: shenlinxing@macklin.cn
Country: China
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LETOPHARM LIMITED

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Email: sales@letopharm.com
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Shanghai Lollane Biological Technology Co.,Ltd.

Tel: 021-52996696，15000506266 15000506266
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Shanghai Beckham Medical Technology Co., Ltd

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SPIRO PHARMA

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Shanghai EFE Biological Technology Co., Ltd.

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Shanghai YuanYe Biotechnology Co., Ltd.

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Shanghai Rechem science Co., Ltd.

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1260533-36-5, TAS-116Related Search:

Futibatinib TAS6417 TAS0728 TAS-102 TAS-301

TAS 116;TAS116

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

TAS-116

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]-

Des-iPr-TAS-116

Pimitespib (TAS-116)

Pimitespib

inhibit,HSP,TAS 116,TAS116,Pimitespib,Heat shock proteins,Inhibitor

Pimitespib, 10 mM in DMSO

Pimitespib (TAS-116) ，S7716

3-Ethyl-4-[4-[4-(1-methylpyrazol-4-yl)imidazol-1-yl]-3-propan-2-ylpyrazolo[3,4-b]pyridin-1-yl]benzamide

1260533-36-5

C25H26N8O