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Literature DB >> 25568641

A Preliminary Assessment of the Structure-Activity Relationship of Benzimidazole-Based Anti-Proliferative Agents.

Leyte L Winfield¹, Dayle M Smith², Kalani Halemano², Carmine S Leggett¹.

Abstract

PDK1 is pivotal in the development and progression of several cancers. A 3D pharmacophore was developed for pyrazole derivatives displaying anti-proliferative activity and PDK1 inhibition. The pharmacophore was utilized in the design of benzimidazole analogs. Our preliminary results indicate the pharmacophore should be useful in designing PDK1 inhibitors and anti-proliferative agents.

Entities: Chemical Disease Gene

Keywords: 3D Pharmacophore; Anti-proliferative; Benzimidazole; PDK1; Prostate cancer; SAR

Year: 2008 PMID： 25568641 PMCID： PMC4283767 DOI： 10.2174/157018008785777324#sthash.5mpkAcrR.dpuf

Source DB: PubMed Journal: Lett Drug Des Discov ISSN： 1570-1808 Impact factor: 1.150

14 in total

1. Scaffold hopping by "fuzzy" pharmacophores and its application to RNA targets.

Authors: Yusuf Tanrikulu; Manuel Nietert; Ute Scheffer; Ewgenij Proschak; Kristina Grabowski; Petra Schneider; Markus Weidlich; Michael Karas; Michael Göbel; Gisbert Schneider
Journal: Chembiochem Date: 2007-11-05 Impact factor: 3.164

2. Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression.

Authors: Marily Theodoropoulou; Jing Zhang; Sandra Laupheimer; Marcelo Paez-Pereda; Christophe Erneux; Tullio Florio; Uberto Pagotto; Günter K Stalla
Journal: Cancer Res Date: 2006-02-01 Impact factor: 12.701

3. Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia.

Authors: Zhihong Zeng; Ismael J Samudio; Weiguo Zhang; Zeev Estrov; Hélène Pelicano; David Harris; Olga Frolova; Numsen Hail; Wenjing Chen; Steven M Kornblau; Peng Huang; Yiling Lu; Gordon B Mills; Michael Andreeff; Marina Konopleva
Journal: Cancer Res Date: 2006-04-01 Impact factor: 12.701

4. Comparison of the ATP binding sites of protein kinases using conformationally diverse bisindolylmaleimides.

Authors: Stephen Bartlett; Godfrey S Beddard; Richard M Jackson; Veysel Kayser; Colin Kilner; Andrew Leach; Adam Nelson; Peter R Oledzki; Peter Parker; Gavin D Reid; Stuart L Warriner
Journal: J Am Chem Soc Date: 2005-08-24 Impact factor: 15.419

5. The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation.

Authors: Edward J McManus; Barry J Collins; Peter R Ashby; Alan R Prescott; Victoria Murray-Tait; Laura J Armit; J Simon C Arthur; Dario R Alessi
Journal: EMBO J Date: 2004-04-29 Impact factor: 11.598

6. In vivo role of the PIF-binding docking site of PDK1 defined by knock-in mutation.

Authors: Barry J Collins; Maria Deak; J Simon C Arthur; Laura J Armit; Dario R Alessi
Journal: EMBO J Date: 2003-08-15 Impact factor: 11.598

Review 7. PDK1, the master regulator of AGC kinase signal transduction.

Authors: Alfonso Mora; David Komander; Daan M F van Aalten; Dario R Alessi
Journal: Semin Cell Dev Biol Date: 2004-04 Impact factor: 7.727

8. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors.

Authors: Jiuxiang Zhu; Jui-Wen Huang; Ping-Hui Tseng; Ya-Ting Yang; Joseph Fowble; Chung-Wai Shiau; Yeng-Jeng Shaw; Samuel K Kulp; Ching-Shih Chen
Journal: Cancer Res Date: 2004-06-15 Impact factor: 12.701

A Preliminary Assessment of the Structure-Activity Relationship of Benzimidazole-Based Anti-Proliferative Agents.

1. Scaffold hopping by "fuzzy" pharmacophores and its application to RNA targets.

2. Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression.

3. Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia.

4. Comparison of the ATP binding sites of protein kinases using conformationally diverse bisindolylmaleimides.

5. The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation.

6. In vivo role of the PIF-binding docking site of PDK1 defined by knock-in mutation.

Review 7. PDK1, the master regulator of AGC kinase signal transduction.

8. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors.

Review 9. PI3K/Akt signalling pathway and cancer.

10. 3-phosphoinositide-dependent protein kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases.

1. Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells.

2. Celecoxib and LLW-3-6 Reduce Survival of Human Glioma Cells Independently and Synergistically with Sulfasalazine.

3. LLW-3-6 and celecoxib impacts growth in prostate cancer cells and subcellular localization of COX-2.