Synonyms: compound 16e [PMID: 30525599] | Jeselhy® | TAS-116 | TAS116
Compound class:
Synthetic organic
Comment: Pimitespib (TAS-116) is an orally bioavailable heat shock protein 90 α/β (HSP90α/β) inhibitor [6], that promotes proteasomal degradation of oncogenic HSP90 client proteins, and induces apoptosis of cells that overexpress (HSP90α/β). Reported to bind at the N-terminal ATP binding site of the target proteins [6]. Pimitespib was developed for potential antineoplastic activity [1,3-5].
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References |
1. Doi T, Kurokawa Y, Sawaki A, Komatsu Y, Ozaka M, Takahashi T, Naito Y, Ohkubo S, Nishida T. (2019)
Efficacy and safety of TAS-116, an oral inhibitor of heat shock protein 90, in patients with metastatic or unresectable gastrointestinal stromal tumour refractory to imatinib, sunitinib and regorafenib: a phase II, single-arm trial. Eur J Cancer, 121: 29-39. [PMID:31536852] |
2. Hoy SM. (2022)
Pimitespib: First Approval. Drugs, 82 (13): 1413-1418. [PMID:35986838] |
3. Kawazoe A, Itahashi K, Yamamoto N, Kotani D, Kuboki Y, Taniguchi H, Harano K, Naito Y, Suzuki M, Fukutani M et al.. (2021)
TAS-116 (Pimitespib), an Oral HSP90 Inhibitor, in Combination with Nivolumab in Patients with Colorectal Cancer and Other Solid Tumors: An Open-Label, Dose-Finding, and Expansion Phase Ib Trial (EPOC1704). Clin Cancer Res, 27 (24): 6709-6715. [PMID:34593531] |
4. Ohkubo S, Kodama Y, Muraoka H, Hitotsumachi H, Yoshimura C, Kitade M, Hashimoto A, Ito K, Gomori A, Takahashi K et al.. (2015)
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, 14 (1): 14-22. [PMID:25416789] |
5. Suzuki R, Hideshima T, Mimura N, Minami J, Ohguchi H, Kikuchi S, Yoshida Y, Gorgun G, Cirstea D, Cottini F et al.. (2015)
Anti-tumor activities of selective HSP90α/β inhibitor, TAS-116, in combination with bortezomib in multiple myeloma. Leukemia, 29 (2): 510-4. [PMID:25306900] |
6. Uno T, Kawai Y, Yamashita S, Oshiumi H, Yoshimura C, Mizutani T, Suzuki T, Chong KT, Shigeno K, Ohkubo M et al.. (2019)
Discovery of 3-Ethyl-4-(3-isopropyl-4-(4-(1-methyl-1 H-pyrazol-4-yl)-1 H-imidazol-1-yl)-1 H-pyrazolo[3,4- b]pyridin-1-yl)benzamide (TAS-116) as a Potent, Selective, and Orally Available HSP90 Inhibitor. J Med Chem, 62 (2): 531-551. [PMID:30525599] |