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Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (OATL4).

ABSTRACT: Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (OATL4).

PROVIDER: PRJNA708286 | ENA |

REPOSITORIES: ENA

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Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (ED).

Project description:Adult T-cell leukaemia-lymphoma (ATL) is a highly chemoresistant malignancy of peripheral T lymphocytes caused by human T-lymphotropic virus type I (HTLV-1). ATL cells constitutively activate anti-apoptotic signals through nuclear factor kappaB (NF-κB)-mediated gene expression. The molecular chaperon heat shock protein 90 (HSP90) plays a crucial role on NF-κB-mediated anti-apoptotic activity in ATL cells and HSP90 inhibitors, such as 17-DMAG and NVP-AUY922, have demonstrated their anti-ATL activities. A novel class of orally active inhibitors of cytosolic HSP90α and β, pimitespib, demonstrated its highly selective anti-ATL cell effects both ex-vivo and in vivo preclinical models. Ten ATL-related cell lines achieved their IC50 below 0.5µM dose of TAS-116 while CD4 lymphocytes derived from healthy donors were less harmed than ATL cells. TAS-116 efficiently induces Tax-degradation and IκB-α accumulation to Tax-positive cell-lines. DNA microarray profiling followed by a variety of pathway analysis revealed that TAS-116 down-regulated NF-κB activating pathways in Tax-positive cells and cell cycle promoting pathways in Tax-negative cells and induces anti-ATL effect. Oral administration of TAS-116 to ATL-cell xenograft model mice also demonstrated the growth inhibitory effects against tumor cells. Consequently, TAS-116, one of the most evolved HSP90 inhibitor, may become a promising option against ATL therapy.

2022-02-18 | GSE168552 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (OATL4).

2022-02-18 | GSE168556 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Su9T01).

2022-02-18 | GSE168558 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (HuT102).

2022-02-18 | GSE168554 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Pt1-3).

2022-02-18 | GSE168557 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (LYM1, KK1).

2022-02-18 | GSE168555 | GEO

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Su9T01).

Project description:Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Su9T01).

| PRJNA708289 | ENA

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (ED).

Project description:Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (ED).

| PRJNA708285 | ENA

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (HuT102).

Project description:Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (HuT102).

| PRJNA708284 | ENA

Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (LYM1, KK1).

Project description:Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (LYM1, KK1).

| PRJNA708287 | ENA

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