Home Cytoskeletal Signaling HSP inhibitor Pimitespib (TAS-116)

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Pimitespib (TAS-116) HSP inhibitor

Cat.No.S7716

Pimitespib (TAS-116) is a novel, small-molecule HSP90 inhibitor which inhibits geldanamycin-FITC binding to HSP90 proteins with Ki values of 34.7 nmol/L, 21.3 nmol/L, >50,000 nmol/L, and >50,000 nmol/L for HSP90α, HSP90β, GRP94, and TRAP1, respectively. Furthermore, this compound does not inhibit other ATPases such as HSP70 (IC50 >200 μmol/L).
Pimitespib (TAS-116) HSP inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 454.53

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability

Quality Control

Batch: S771601 DMSO]91 mg/mL]false]Ethanol]11 mg/mL]false]Water]Insoluble]false Purity: 99.32%
99.32

Chemical Information, Storage & Stability

Molecular Weight 454.53 Formula

C25H26N8O

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 1260533-36-5 -- Storage of Stock Solutions

Synonyms N/A Smiles CCC1=C(C=CC(=C1)C(=O)N)N2C3=NC=CC(=C3C(=N2)C(C)C)N4C=C(N=C4)C5=CN(N=C5)C

Solubility

In vitro
Batch:

DMSO : 91 mg/mL (200.2 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 11 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
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Mechanism of Action

Targets/IC50/Ki
HSP90β [1]
(Cell-free assay)
21.3 nM(Ki)
HSP90α [1]
(Cell-free assay )
34.7 nM(Ki)
In vitro

Pimitespib (TAS-116) is a selective inhibitor of cytosolic HSP90α and β that does not inhibit HSP90 paralogs such as endoplasmic reticulum GRP94 or mitochondrial TRAP1. Treatment of HCT116 cells with 0.3 μmol/L of this compound for 8 hours results in reduced levels of DDR1, which interacts with HSP90α and induction of HSP70, which is a surrogate marker of cytosolic HSP90 inhibition[1].
In vivo

Oral administration of Pimitespib (TAS-116) leads to tumor shrinkage in human tumor xenograft mouse models accompanied by depletion of multiple HSP90 clients. In a rat model, the antitumor activity of this compound is accompanied by a higher distribution in subcutaneously xenografted NCI-H1975 non-small cell lung carcinoma tumors than in retina. It shows activity against orthotopically transplanted NCI-H1975 lung tumors. Pharmacokinetic profiling in rodent and nonrodent species shows that TAS-116 is orally absorbed and had a bioavailability of almost 100% in mice, 69.0% in rats, and 73.9% in dogs without special formulation. In a HER2-expressing NCI-N87 human gastric cancer xenograft mouse model, chronic administration is tolerable, with the average weight loss in mice not exceeding 10% during the treatment period[1].
References

Applications

Methods Biomarkers Images PMID
Western blot p-B-Raf / B-raf / p-C-Raf / C-Raf / p-MEK / MEK / p-ERK / ERK / p-AKT / AKT / PARP S7716-WB1 26630652
Growth inhibition assay Cell viability S7716-viability1 26630652

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05655598 Recruiting
Advanced Breast Cancer|Treatment-Refractory Solid Tumors|Retinoblastoma Deficiency|SCLC|Soft Tissue Sarcoma|Endometrial Cancer|Bladder Cancer
Brown University
 September 12 2023 Phase 1
NCT02965885 Completed
Advanced Solid Tumors
Taiho Oncology Inc.
 July 10 2017 Phase 1

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