tas-116 and quinoline

tas-116 has been researched along with quinoline* in 1 studies

Other Studies

1 other study(ies) available for tas-116 and quinoline

Article	Year
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. Journal of medicinal chemistry, 2019, 01-24, Volume: 62, Issue:2 The molecular chaperone heat shock protein 90 (HSP90) is a promising target for cancer therapy, as it assists in the stabilization of cancer-related proteins, promoting cancer cell growth, and survival. A novel series of HSP90 inhibitors were discovered by structure-activity relationship (SAR)-based optimization of an initial hit compound 11a having a 4-(4-(quinolin-3-yl)-1 H-indol-1-yl)benzamide structure. The pyrazolo[3,4- b]pyridine derivative, 16e (TAS-116), is a selective inhibitor of HSP90α and HSP90β among the HSP90 family proteins and exhibits oral availability in mice. The X-ray cocrystal structure of the 16e analogue 16d demonstrated a unique binding mode at the N-terminal ATP binding site. Oral administration of 16e demonstrated potent antitumor effects in an NCI-H1975 xenograft mouse model without significant body weight loss. Topics: Administration, Oral; Animals; Antineoplastic Agents; Benzamides; Binding Sites; Cell Line, Tumor; Crystallography, X-Ray; Drug Design; Drug Screening Assays, Antitumor; HSP90 Heat-Shock Proteins; Humans; Mice; Mice, Nude; Molecular Conformation; Molecular Dynamics Simulation; Neoplasms; Pyrazoles; Quinolines; Recombinant Proteins; Solubility; Structure-Activity Relationship	2019

Article

Year

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.

Journal of medicinal chemistry, 2019, 01-24, Volume: 62, Issue:2

The molecular chaperone heat shock protein 90 (HSP90) is a promising target for cancer therapy, as it assists in the stabilization of cancer-related proteins, promoting cancer cell growth, and survival. A novel series of HSP90 inhibitors were discovered by structure-activity relationship (SAR)-based optimization of an initial hit compound 11a having a 4-(4-(quinolin-3-yl)-1 H-indol-1-yl)benzamide structure. The pyrazolo[3,4- b]pyridine derivative, 16e (TAS-116), is a selective inhibitor of HSP90α and HSP90β among the HSP90 family proteins and exhibits oral availability in mice. The X-ray cocrystal structure of the 16e analogue 16d demonstrated a unique binding mode at the N-terminal ATP binding site. Oral administration of 16e demonstrated potent antitumor effects in an NCI-H1975 xenograft mouse model without significant body weight loss.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Benzamides; Binding Sites; Cell Line, Tumor; Crystallography, X-Ray; Drug Design; Drug Screening Assays, Antitumor; HSP90 Heat-Shock Proteins; Humans; Mice; Mice, Nude; Molecular Conformation; Molecular Dynamics Simulation; Neoplasms; Pyrazoles; Quinolines; Recombinant Proteins; Solubility; Structure-Activity Relationship

2019