Synthesis and biological evaluation of solubilized sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474.

Giddens, Anna C; Gamage, Swarna A; Kendall, Jackie D; Lee, Woo-Jeong; Baguley, Bruce C; Buchanan, Christina M; Jamieson, Stephen MF; Dickson, James MJ; Shepherd, Peter R; Denny, William A; Rewcastle, Gordon W

dc.contributor.author	Giddens, Anna C
dc.contributor.author	Gamage, Swarna A
dc.contributor.author	Kendall, Jackie D
dc.contributor.author	Lee, Woo-Jeong
dc.contributor.author	Baguley, Bruce C
dc.contributor.author	Buchanan, Christina M
dc.contributor.author	Jamieson, Stephen MF
dc.contributor.author	Dickson, James MJ
dc.contributor.author	Shepherd, Peter R
dc.contributor.author	Denny, William A
dc.contributor.author	Rewcastle, Gordon W
dc.coverage.spatial	England
dc.date.accessioned	2022-02-09T21:13:38Z
dc.date.available	2022-02-09T21:13:38Z
dc.date.issued	2019-4
dc.identifier.citation	Bioorganic & medicinal chemistry 27(8):1529-1545 Apr 2019
dc.identifier.issn	0968-0896
dc.identifier.uri	https://hdl.handle.net/2292/58127
dc.description.abstract	Replacing one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 with a variety of sulfonamide-linked solubilizing substituents produced a new class of active and potent PI3Kα inhibitors, with several derivatives demonstrating high PI3Kα enzyme potency and good cellular potency in two human derived cell lines. The overall results suggest a preference for linear and somewhat flexible solubilizing functions. From this series, compound 16, also known as SN32976, was selected for advanced preclinical evaluation.
dc.format.medium	Print-Electronic
dc.language	eng
dc.publisher	Elsevier BV
dc.relation.ispartofseries	Bioorganic & medicinal chemistry
dc.rights	Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.rights.uri	https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
dc.subject	Cell Line, Tumor
dc.subject	Animals
dc.subject	Humans
dc.subject	Mice
dc.subject	Neoplasms
dc.subject	Sulfonamides
dc.subject	Triazines
dc.subject	Protein Subunits
dc.subject	Antineoplastic Agents
dc.subject	Transplantation, Heterologous
dc.subject	Drug Evaluation, Preclinical
dc.subject	Inhibitory Concentration 50
dc.subject	Cell Proliferation
dc.subject	Structure-Activity Relationship
dc.subject	Female
dc.subject	Phosphatidylinositol 3-Kinases
dc.subject	Phosphoinositide-3 Kinase Inhibitors
dc.subject	PI3K
dc.subject	Phosphatidylinositol 3-kinase
dc.subject	SN32976
dc.subject	ZSTK474
dc.subject	p110α
dc.subject	Animals
dc.subject	Antineoplastic Agents
dc.subject	Cell Line, Tumor
dc.subject	Cell Proliferation
dc.subject	Drug Evaluation, Preclinical
dc.subject	Female
dc.subject	Humans
dc.subject	Inhibitory Concentration 50
dc.subject	Mice
dc.subject	Neoplasms
dc.subject	Phosphatidylinositol 3-Kinases
dc.subject	Phosphoinositide-3 Kinase Inhibitors
dc.subject	Protein Subunits
dc.subject	Structure-Activity Relationship
dc.subject	Sulfonamides
dc.subject	Transplantation, Heterologous
dc.subject	Triazines
dc.subject	Science & Technology
dc.subject	Life Sciences & Biomedicine
dc.subject	Physical Sciences
dc.subject	Biochemistry & Molecular Biology
dc.subject	Chemistry, Medicinal
dc.subject	Chemistry, Organic
dc.subject	Pharmacology & Pharmacy
dc.subject	Chemistry
dc.subject	Phosphatidylinositol 3-kinase
dc.subject	PI3K
dc.subject	p110 alpha
dc.subject	ZSTK474
dc.subject	SN32976
dc.subject	PHOSPHOINOSITIDE 3-KINASE
dc.subject	CLASS-I
dc.subject	PIK3CA GENE
dc.subject	ISOFORM
dc.subject	PATHWAY
dc.subject	KINASE
dc.subject	MECHANISMS
dc.subject	P110-ALPHA
dc.subject	DISCOVERY
dc.subject	0601 Biochemistry and Cell Biology
dc.subject	5.1 Pharmaceuticals
dc.subject	0304 Medicinal and Biomolecular Chemistry
dc.subject	0305 Organic Chemistry
dc.subject	1115 Pharmacology and Pharmaceutical Sciences
dc.title	Synthesis and biological evaluation of solubilized sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474.
dc.type	Journal Article
dc.identifier.doi	10.1016/j.bmc.2019.02.050
pubs.issue	8
pubs.begin-page	1529
pubs.volume	27
dc.date.updated	2022-01-10T01:05:38Z
dc.rights.holder	Copyright: 2019 Elsevier Ltd. All rights reserved.	en
pubs.author-url	https://www.ncbi.nlm.nih.gov/pubmed/30850264
pubs.end-page	1545
pubs.publication-status	Published
dc.rights.accessrights	http://purl.org/eprint/accessRights/RestrictedAccess	en
pubs.subtype	Research Support, Non-U.S. Gov't
pubs.subtype	Journal Article
pubs.elements-id	765971
dc.identifier.eissn	1464-3391
dc.identifier.pii	S0968-0896(18)32045-5