Literature DB >> 26985315

Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of NaV1.7 with Efficacy in Rodent Pain Models.

Thilo Focken1, Shifeng Liu1, Navjot Chahal1, Maxim Dauphinais1, Michael E Grimwood1, Sultan Chowdhury1, Ivan Hemeon1, Paul Bichler1, David Bogucki1, Matthew Waldbrook1, Girish Bankar1, Luis E Sojo1, Clint Young1, Sophia Lin1, Noah Shuart1, Rainbow Kwan1, Jodie Pang2, Jae H Chang2, Brian S Safina2, Daniel P Sutherlin2, J P Johnson1, Christoph M Dehnhardt1, Tarek S Mansour1, Renata M Oballa1, Charles J Cohen1, C Lee Robinette1.   

Abstract

We report on a novel series of aryl sulfonamides that act as nanomolar potent, isoform-selective inhibitors of the human sodium channel hNaV1.7. The optimization of these inhibitors is described. We aimed to improve potency against hNaV1.7 while minimizing off-target safety concerns and generated compound 3. This agent displayed significant analgesic effects in rodent models of acute and inflammatory pain and demonstrated that binding to the voltage sensor domain 4 site of NaV1.7 leads to an analgesic effect in vivo. Our findings corroborate the importance of hNaV1.7 as a drug target for the treatment of pain.

Entities:  

Keywords:  NaV1.5; NaV1.7; Sodium channel; aryl sulfonamide; cold allodynia; formalin model; pain

Year:  2016        PMID： 26985315      PMCID： PMC4789675          DOI： 10.1021/acsmedchemlett.5b00447

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


  20 in total

1.  An automated flinch detecting system for use in the formalin nociceptive bioassay.

Authors:  T L Yaksh; G Ozaki; D McCumber; M Rathbun; C Svensson; S Malkmus; M C Yaksh
Journal:  J Appl Physiol (1985)       Date:  2001-06

2.  A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief.

Authors:  Jun-Ho Lee; Chul-Kyu Park; Gang Chen; Qingjian Han; Rou-Gang Xie; Tong Liu; Ru-Rong Ji; Seok-Yong Lee
Journal:  Cell       Date:  2014-05-22       Impact factor: 41.582

Review 3.  Recent progress in sodium channel modulators for pain.

Authors:  Sharan K Bagal; Mark L Chapman; Brian E Marron; Rebecca Prime; R Ian Storer; Nigel A Swain
Journal:  Bioorg Med Chem Lett       Date:  2014-06-21       Impact factor: 2.823

Review 4.  Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications.

Authors:  Manuel de Lera Ruiz; Richard L Kraus
Journal:  J Med Chem       Date:  2015-05-14       Impact factor: 7.446

Review 5.  Inhibitors of voltage-gated sodium channel Nav1.7: patent applications since 2010.

Authors:  Shaoyi Sun; Charles J Cohen; Christoph M Dehnhardt
Journal:  Pharm Pat Anal       Date:  2014-09

6.  The discovery of benzenesulfonamide-based potent and selective inhibitors of voltage-gated sodium channel Na(v)1.7.

Authors:  Shaoyi Sun; Qi Jia; Alla Y Zenova; Mikhail Chafeev; Zaihui Zhang; Sophia Lin; Rainbow Kwan; Mike E Grimwood; Sultan Chowdhury; Clint Young; Charles J Cohen; Renata M Oballa
Journal:  Bioorg Med Chem Lett       Date:  2014-08-14       Impact factor: 2.823

7.  Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist.

Authors:  Shivani Ahuja; Susmith Mukund; Lunbin Deng; Kuldip Khakh; Elaine Chang; Hoangdung Ho; Stephanie Shriver; Clint Young; Sophia Lin; J P Johnson; Ping Wu; Jun Li; Mary Coons; Christine Tam; Bobby Brillantes; Honorio Sampang; Kyle Mortara; Krista K Bowman; Kevin R Clark; Alberto Estevez; Zhiwei Xie; Henry Verschoof; Michael Grimwood; Christoph Dehnhardt; Jean-Christophe Andrez; Thilo Focken; Daniel P Sutherlin; Brian S Safina; Melissa A Starovasnik; Daniel F Ortwine; Yvonne Franke; Charles J Cohen; David H Hackos; Christopher M Koth; Jian Payandeh
Journal:  Science       Date:  2015-12-18       Impact factor: 47.728

Review 8.  Neurological perspectives on voltage-gated sodium channels.

Authors:  Niels Eijkelkamp; John E Linley; Mark D Baker; Michael S Minett; Roman Cregg; Robert Werdehausen; François Rugiero; John N Wood
Journal:  Brain       Date:  2012-09       Impact factor: 13.501

9.  Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons.

Authors:  Michael S Minett; Mohammed A Nassar; Anna K Clark; Gayle Passmore; Anthony H Dickenson; Fan Wang; Marzia Malcangio; John N Wood
Journal:  Nat Commun       Date:  2012-04-24       Impact factor: 14.919

10.  Pain without nociceptors? Nav1.7-independent pain mechanisms.

Authors:  Michael S Minett; Sarah Falk; Sonia Santana-Varela; Yury D Bogdanov; Mohammed A Nassar; Anne-Marie Heegaard; John N Wood
Journal:  Cell Rep       Date:  2014-01-16       Impact factor: 9.423
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  15 in total

Review 1.  Breaking barriers to novel analgesic drug development.

Authors:  Ajay S Yekkirala; David P Roberson; Bruce P Bean; Clifford J Woolf
Journal:  Nat Rev Drug Discov       Date:  2017-06-09       Impact factor: 84.694

2.  Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement.

Authors:  Isaac E Marx; Thomas A Dineen; Jessica Able; Christiane Bode; Howard Bregman; Margaret Chu-Moyer; Erin F DiMauro; Bingfan Du; Robert S Foti; Robert T Fremeau; Hua Gao; Hakan Gunaydin; Brian E Hall; Liyue Huang; Thomas Kornecook; Charles R Kreiman; Daniel S La; Joseph Ligutti; Min-Hwa Jasmine Lin; Dong Liu; Jeff S McDermott; Bryan D Moyer; Emily A Peterson; Jonathan T Roberts; Paul Rose; Jean Wang; Beth D Youngblood; Violeta Yu; Matthew M Weiss
Journal:  ACS Med Chem Lett       Date:  2016-09-21       Impact factor: 4.345

3.  The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics.

Authors:  D C Pryde; N A Swain; P A Stupple; C W West; B Marron; C J Markworth; D Printzenhoff; Z Lin; P J Cox; R Suzuki; S McMurray; G J Waldron; C E Payne; J S Warmus; M L Chapman
Journal:  Medchemcomm       Date:  2017-04-28       Impact factor: 3.597

4.  A novel substituted aminoquinoline selectively targets voltage-sensitive sodium channel isoforms and NMDA receptor subtypes and alleviates chronic inflammatory and neuropathic pain.

Authors:  Boris Tabakoff; Wenhua Ren; Lauren Vanderlinden; Lawrence D Snell; Christopher J Matheson; Ze-Jun Wang; Rock Levinson; C Thetford Smothers; John J Woodward; Yumiko Honse; David Lovinger; Anthony M Rush; William A Sather; Daniel L Gustafson; Paula L Hoffman
Journal:  Eur J Pharmacol       Date:  2016-05-05       Impact factor: 4.432

Review 5.  Inhibition of NaV1.7: the possibility of ideal analgesics.

Authors:  Yutaka Kitano; Tsuyoshi Shinozuka
Journal:  RSC Med Chem       Date:  2022-08-01

6.  Lidocaine Binding Enhances Inhibition of Nav1.7 Channels by the Sulfonamide PF-05089771.

Authors:  Sooyeon Jo; Bruce P Bean
Journal:  Mol Pharmacol       Date:  2020-03-19       Impact factor: 4.436

7.  Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a.

Authors:  Jennifer R Deuis; Zoltan Dekan; Joshua S Wingerd; Jennifer J Smith; Nehan R Munasinghe; Rebecca F Bhola; Wendy L Imlach; Volker Herzig; David A Armstrong; K Johan Rosengren; Frank Bosmans; Stephen G Waxman; Sulayman D Dib-Hajj; Pierre Escoubas; Michael S Minett; Macdonald J Christie; Glenn F King; Paul F Alewood; Richard J Lewis; John N Wood; Irina Vetter
Journal:  Sci Rep       Date:  2017-01-20       Impact factor: 4.379

8.  Insensitivity to pain induced by a potent selective closed-state Nav1.7 inhibitor.

Authors:  M Flinspach; Q Xu; A D Piekarz; R Fellows; R Hagan; A Gibbs; Y Liu; R A Neff; J Freedman; W A Eckert; M Zhou; R Bonesteel; M W Pennington; K A Eddinger; T L Yaksh; M Hunter; R V Swanson; A D Wickenden
Journal:  Sci Rep       Date:  2017-01-03       Impact factor: 4.379

9.  Antinociceptive properties of an isoform-selective inhibitor of Nav1.7 derived from saxitoxin in mouse models of pain.

Authors:  Jacob T Beckley; Hassan Pajouhesh; George Luu; Sheri Klas; Anton Delwig; Dennis Monteleone; Xiang Zhou; Denise Giuvelis; Ian D Meng; David C Yeomans; John C Hunter; John V Mulcahy
Journal:  Pain       Date:  2021-04-01       Impact factor: 7.926

10.  Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors.

Authors:  Sara I Liin; Per-Eric Lund; Johan E Larsson; Johan Brask; Björn Wallner; Fredrik Elinder
Journal:  J Gen Physiol       Date:  2018-07-12       Impact factor: 4.086
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