Literature DB >> 26985295

Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway.

Celeste Alverez1, Stacie L Bulfer2, Ramappa Chakrasali3, Michael S Chimenti2, Raymond J Deshaies4, Neal Green5, Mark Kelly2, Matthew G LaPorte6, Taber S Lewis6, Mary Liang1, William J Moore5, R Jeffrey Neitz2, Vsevolod A Peshkov6, Michael A Walters3, Feng Zhang6, Michelle R Arkin2, Peter Wipf1, Donna M Huryn1.   

Abstract

A high-throughput screen to discover inhibitors of p97 ATPase activity identified an indole amide that bound to an allosteric site of the protein. Medicinal chemistry optimization led to improvements in potency and solubility. Indole amide 3 represents a novel uncompetitive inhibitor with excellent physical and pharmaceutical properties that can be used as a starting point for drug discovery efforts.

Entities:  

Keywords:  AAA ATPase; allosteric inhibitor; indole amide; p97 inhibitor; protein homeostasis; ubiquitin pathway modulator

Year:  2015        PMID： 26985295      PMCID： PMC4753542          DOI： 10.1021/acsmedchemlett.5b00396

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  22 in total

1.  p97, a protein coping with multiple identities.

Authors:  Philip G Woodman
Journal:  J Cell Sci       Date:  2003-11-01       Impact factor: 5.285

2.  Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death.

Authors:  Paola Magnaghi; Roberto D'Alessio; Barbara Valsasina; Nilla Avanzi; Simona Rizzi; Daniela Asa; Fabio Gasparri; Liviana Cozzi; Ulisse Cucchi; Christian Orrenius; Paolo Polucci; Dario Ballinari; Claudia Perrera; Antonella Leone; Giovanni Cervi; Elena Casale; Yang Xiao; Chihunt Wong; Daniel J Anderson; Arturo Galvani; Daniele Donati; Tom O'Brien; Peter K Jackson; Antonella Isacchi
Journal:  Nat Chem Biol       Date:  2013-07-28       Impact factor: 15.040

3.  Group epitope mapping by saturation transfer difference NMR to identify segments of a ligand in direct contact with a protein receptor.

Authors:  M Mayer; B Meyer
Journal:  J Am Chem Soc       Date:  2001-06-27       Impact factor: 15.419

Review 4.  Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system.

Authors:  Hemmo Meyer; Monika Bug; Sebastian Bremer
Journal:  Nat Cell Biol       Date:  2012-02-02       Impact factor: 28.824

5.  Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways.

Authors:  Tsui-Fen Chou; Steve J Brown; Dmitriy Minond; Brian E Nordin; Kelin Li; Amanda C Jones; Peter Chase; Patrick R Porubsky; Brian M Stoltz; Frank J Schoenen; Matthew P Patricelli; Peter Hodder; Hugh Rosen; Raymond J Deshaies
Journal:  Proc Natl Acad Sci U S A       Date:  2011-03-07       Impact factor: 11.205

6.  2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97).

Authors:  Matthew G Bursavich; Daniel P Parker; J Adam Willardsen; Zhong-Hua Gao; Thaylon Davis; Kirill Ostanin; Rosann Robinson; Ashley Peterson; Daniel M Cimbora; Ju-Fen Zhu; Burt Richards
Journal:  Bioorg Med Chem Lett       Date:  2010-01-21       Impact factor: 2.823

7.  Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains.

Authors:  Tsui-Fen Chou; Stacie L Bulfer; Conrad C Weihl; Kelin Li; Lev G Lis; Michael A Walters; Frank J Schoenen; Henry J Lin; Raymond J Deshaies; Michelle R Arkin
Journal:  J Mol Biol       Date:  2014-05-27       Impact factor: 5.469

8.  Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083).

Authors:  Han-Jie Zhou; Jinhai Wang; Bing Yao; Steve Wong; Stevan Djakovic; Brajesh Kumar; Julie Rice; Eduardo Valle; Ferdie Soriano; Mary-Kamala Menon; Antonett Madriaga; Szerenke Kiss von Soly; Abhinav Kumar; Francesco Parlati; F Michael Yakes; Laura Shawver; Ronan Le Moigne; Daniel J Anderson; Mark Rolfe; David Wustrow
Journal:  J Med Chem       Date:  2015-12-04       Impact factor: 7.446

Review 9.  Molecular perspectives on p97-VCP: progress in understanding its structure and diverse biological functions.

Authors:  Qing Wang; Changcheng Song; Chou-Chi H Li
Journal:  J Struct Biol       Date:  2004 Apr-May       Impact factor: 2.867

Review 10.  Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy.

Authors:  Raymond J Deshaies
Journal:  BMC Biol       Date:  2014-11-11       Impact factor: 7.431
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  11 in total

1.  Palladium/Norbornene Cooperative Catalysis.

Authors:  Jianchun Wang; Guangbin Dong
Journal:  Chem Rev       Date:  2019-04-25       Impact factor: 60.622

2.  A threonine turnstile defines a dynamic amphiphilic binding motif in the AAA ATPase p97 allosteric binding site.

Authors:  James C Burnett; Chaemin Lim; Brian D Peyser; Lalith P Samankumara; Marina Kovaliov; Raffaele Colombo; Stacie L Bulfer; Matthew G LaPorte; Ann R Hermone; Connor F McGrath; Michelle R Arkin; Rick Gussio; Donna M Huryn; Peter Wipf
Journal:  Org Biomol Chem       Date:  2017-05-16       Impact factor: 3.876

3.  VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase-mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal.

Authors:  Prabhakar Bastola; Lisa Neums; Frank J Schoenen; Jeremy Chien
Journal:  Mol Oncol       Date:  2016-09-28       Impact factor: 6.603

Review 4.  Modulating protein-protein interaction networks in protein homeostasis.

Authors:  Mengqi Zhong; Gregory M Lee; Eline Sijbesma; Christian Ottmann; Michelle R Arkin
Journal:  Curr Opin Chem Biol       Date:  2019-03-23       Impact factor: 8.822

5.  Optimization of pyrazole-containing 1,2,4-triazolo-[3,4-b]thiadiazines, a new class of STAT3 pathway inhibitors.

Authors:  Matthew G LaPorte; Zhuzhu Wang; Raffaele Colombo; Atefeh Garzan; Vsevolod A Peshkov; Mary Liang; Paul A Johnston; Mark E Schurdak; Malabika Sen; Daniel P Camarco; Yun Hua; Netanya I Pollock; John S Lazo; Jennifer R Grandis; Peter Wipf; Donna M Huryn
Journal:  Bioorg Med Chem Lett       Date:  2016-06-09       Impact factor: 2.823

Review 6.  Targeting p97 to Disrupt Protein Homeostasis in Cancer.

Authors:  Pratikkumar Harsukhbhai Vekaria; Trisha Home; Scott Weir; Frank J Schoenen; Rekha Rao
Journal:  Front Oncol       Date:  2016-08-03       Impact factor: 6.244

7.  Valosin-containing Protein is a Target of 5'-l Fuligocandin B and Enhances TRAIL Resistance in Cancer Cells.

Authors:  Midori A Arai; Shota Taguchi; Kazuhiro Komatsuzaki; Kento Uchiyama; Ayaka Masuda; Mana Sampei; Mamoru Satoh; Sayaka Kado; Masami Ishibashi
Journal:  ChemistryOpen       Date:  2016-10-24       Impact factor: 2.911

Review 8.  The AAA+ ATPase p97, a cellular multitool.

Authors:  Lasse Stach; Paul S Freemont
Journal:  Biochem J       Date:  2017-08-17       Impact factor: 3.857

9.  Optimization of Phenyl Indole Inhibitors of the AAA+ ATPase p97.

Authors:  Matthew G LaPorte; James C Burnett; Raffaele Colombo; Stacie L Bulfer; Celeste Alverez; Tsui-Fen Chou; R Jeffrey Neitz; Neal Green; William J Moore; Zhizhou Yue; Shan Li; Michelle R Arkin; Peter Wipf; Donna M Huryn
Journal:  ACS Med Chem Lett       Date:  2018-09-18       Impact factor: 4.345

10.  A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells.

Authors:  Gang Zhang; Shan Li; Feng Wang; Amanda C Jones; Alexander F G Goldberg; Benjamin Lin; Scott Virgil; Brian M Stoltz; Raymond J Deshaies; Tsui-Fen Chou
Journal:  Eur J Med Chem       Date:  2021-01-02       Impact factor: 6.514
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