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Discovery of Arylsulfonamide Nav1.7 Inhibitors: IVIVC, MPO Methods, and Optimization of Selectivity Profile.
Roecker AJ, Layton ME, Pero JE, Kelly MJ 3rd, Greshock TJ, Kraus RL, Li Y, Klein R, Clements M, Daley C, Jovanovska A, Ballard JE, Wang D, Zhao F, Brunskill APJ, Peng X, Wang X, Sun H, Houghton AK, Burgey CS. Roecker AJ, et al. Among authors: klein r. ACS Med Chem Lett. 2021 Jun 1;12(6):1038-1049. doi: 10.1021/acsmedchemlett.1c00218. eCollection 2021 Jun 10. ACS Med Chem Lett. 2021. PMID: 34141090 Free PMC article.
Benzoxazolinone aryl sulfonamides as potent, selective Nav1.7 inhibitors with in vivo efficacy in a preclinical pain model.
Pero JE, Rossi MA, Lehman HDGF, Kelly MJ 3rd, Mulhearn JJ, Wolkenberg SE, Cato MJ, Clements MK, Daley CJ, Filzen T, Finger EN, Gregan Y, Henze DA, Jovanovska A, Klein R, Kraus RL, Li Y, Liang A, Majercak JM, Panigel J, Urban MO, Wang J, Wang YH, Houghton AK, Layton ME. Pero JE, et al. Among authors: klein r. Bioorg Med Chem Lett. 2017 Jun 15;27(12):2683-2688. doi: 10.1016/j.bmcl.2017.04.040. Epub 2017 Apr 22. Bioorg Med Chem Lett. 2017. PMID: 28465103
Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
Roecker AJ, Egbertson M, Jones KLG, Gomez R, Kraus RL, Li Y, Koser AJ, Urban MO, Klein R, Clements M, Panigel J, Daley C, Wang J, Finger EN, Majercak J, Santarelli V, Gregan I, Cato M, Filzen T, Jovanovska A, Wang YH, Wang D, Joyce LA, Sherer EC, Peng X, Wang X, Sun H, Coleman PJ, Houghton AK, Layton ME. Roecker AJ, et al. Among authors: klein r. Bioorg Med Chem Lett. 2017 May 15;27(10):2087-2093. doi: 10.1016/j.bmcl.2017.03.085. Epub 2017 Mar 30. Bioorg Med Chem Lett. 2017. PMID: 28389149
Nav1.7 target modulation and efficacy can be measured in nonhuman primate assays.
Kraus RL, Zhao F, Pall PS, Zhou D, Vardigan JD, Danziger A, Li Y, Daley C, Ballard JE, Clements MK, Klein RM, Holahan MA, Greshock TJ, Kim RM, Layton ME, Burgey CS, Serra J, Henze DA, Houghton AK. Kraus RL, et al. Sci Transl Med. 2021 May 19;13(594):eaay1050. doi: 10.1126/scitranslmed.aay1050. Sci Transl Med. 2021. PMID: 34011626
Association of respiratory failure with inhibition of NaV1.6 in the phrenic nerve.
Klein RM, Layton ME, Regan H, Regan CP, Li Y, Filzen T, Cato M, Clements MK, Wang J, Sanoja R, Greshock TJ, Roecker AJ, Pero JE, Kim R, Burgey C, John CT, Wang YH, Bhandari N, Struyk A, Kraus RL, Henze DA, Houghton AK. Klein RM, et al. Channels (Austin). 2022 Dec;16(1):230-243. doi: 10.1080/19336950.2022.2122309. Channels (Austin). 2022. PMID: 36239534 Free PMC article.
Development of ProTx-II Analogues as Highly Selective Peptide Blockers of Nav1.7 for the Treatment of Pain.
Adams GL, Pall PS, Grauer SM, Zhou X, Ballard JE, Vavrek M, Kraus RL, Morissette P, Li N, Colarusso S, Bianchi E, Palani A, Klein R, John CT, Wang D, Tudor M, Nolting AF, Biba M, Nowak T, Makarov AA, Reibarkh M, Buevich AV, Zhong W, Regalado EL, Wang X, Gao Q, Shahripour A, Zhu Y, de Simone D, Frattarelli T, Pasquini NM, Magotti P, Iaccarino R, Li Y, Solly K, Lee KJ, Wang W, Chen F, Zeng H, Wang J, Regan H, Amin RP, Regan CP, Burgey CS, Henze DA, Sun C, Tellers DM. Adams GL, et al. Among authors: klein r. J Med Chem. 2022 Jan 13;65(1):485-496. doi: 10.1021/acs.jmedchem.1c01570. Epub 2021 Dec 21. J Med Chem. 2022. PMID: 34931831
5,354 results