Author
Patrick Lee Burk
Bio: Patrick Lee Burk is an academic researcher. The author has contributed to research in topics: Camptothecin. The author has an hindex of 3, co-authored 5 publications receiving 51 citations.
Topics: Camptothecin
Papers
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29 citations
17 citations
3 citations
Patent•
15 Jul 1992
3 citations
Patent•
23 Sep 1991
TL;DR: In this article, the authors decrit un procede de preparation d'analogues de camptothecine solubles dans l'eau, and compris des procedes de preparation des produits intermediaires, and les composes prepares selon ledit procede.
Abstract: On decrit un procede de preparation d'analogues de camptothecine solubles dans l'eau, y compris des procedes de preparation des produits intermediaires, et les composes prepares selon ledit procede. Des analogues de camptothecine solubles dans l'eau et pouvant etre utilises pour inhiber la croissance de cellules tumorales sensibles a de tels analogues sont prepares.
Cited by
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606 citations
179 citations
TL;DR: A novel class of heat shock protein 90 (Hsp90) inhibitors was developed from an unbiased screen to identify protein targets for a diverse compound library, and optimized analogues exhibited nanomolar antiproliferative activity across multiple cancer cell lines.
Abstract: A novel class of heat shock protein 90 (Hsp90) inhibitors was developed from an unbiased screen to identify protein targets for a diverse compound library These indol-4-one and indazol-4-one derived 2-aminobenzamides showed strong binding affinity to Hsp90, and optimized analogues exhibited nanomolar antiproliferative activity across multiple cancer cell lines Heat shock protein 70 (Hsp70) induction and specific client protein degradation in cells on treatment with the inhibitors supported Hsp90 inhibition as the mechanism of action Computational chemistry and X-ray crystallographic analysis of selected member compounds clearly defined the protein-inhibitor interaction and assisted the design of analogues 4-[6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]-2-[(trans-4-hydroxycyclohexyl)amino]benzamide (SNX-2112, 9) was identified as highly selective and potent (IC(50) Her2 = 11 nM, HT-29 = 3 nM); its prodrug amino-acetic acid 4-[2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-phenylamino]-cyclohexyl ester methanesulfonate (SNX-5422, 10) was orally bioavailable and efficacious in a broad range of xenograft tumor models (eg 67% growth delay in a HT-29 model) and is now in multiple phase I clinical trials
162 citations
99 citations
TL;DR: The synthesis of chemical tools for three Hsp90 inhibitor classes will be useful for probing tumor-by-tumor the HSp90 complexes isolated by specific inhibitors, and will lead to better understanding of tumor specific molecular markers to aid in their clinical development.
49 citations