Selected Publications
Journigan et al, ACS Chem Neurosci, 2020.
Structure–activity relationship studies of a reported menthol-based transient receptor potential cation channel subfamily M member 8 channel (TRPM8) antagonist, guided by computational simulations and structure-based design, uncovers a novel series of TRPM8 antagonists with >10-fold selectivity versus related TRP subtypes. Spiro[4.5]decan-8-yl analogue 14 inhibits icilin-evoked Ca2+ entry in HEK-293 cells stably expressing human TRPM8 (hTRPM8) with an IC50 of 2.4 ± 1.0 nM, while in whole-cell patch-clamp recordings this analogue inhibits menthol-evoked currents with a hTRPM8 IC50 of 64 ± 2 nM. Molecular dynamics (MD) simulations of compound 14 in our homology model of hTRPM8 suggest that this antagonist forms extensive hydrophobic contacts within the orthosteric site. In the wet dog shakes (WDS) assay, compound 14 dose-dependently blocks icilin-triggered shaking behaviors in mice. Upon local administration, compound 14 dose dependently inhibits cold allodynia evoked by the chemotherapy oxaliplatin in a murine model of peripheral neuropathy at microgram doses. Our findings suggest that 14 and other biphenyl amide analogues within our series can find utility as potent antagonist chemical probes derived from (−)-menthol as well as small molecule therapeutic scaffolds for chemotherapy-induced peripheral neuropathy (CIPN) and other sensory neuropathies.
https://pubs.acs.org/doi/10.1021/acschemneuro.9b00404
Journigan et al, ACS Med Chem Lett, 2021.
TRPM8 antagonists derived from its cognate ligand, (−)-menthol, are underrepresented. We determine the absolute stereochemistry of a well-known TRPM8 antagonist, (−)-menthyl 1, using VCD and 2D NMR. We explore 1 for its antagonist effects of the human TRPM8 (hTRPM8) orthologue to uncover species-dependent inhibition versus rat channels. (−)-Menthyl 1 inhibits menthol- and icilin-evoked Ca2+ responses at hTRPM8 with IC50 values of 805 ± 200 nM and 1.8 ± 0.6 μM, respectively, while more potently inhibiting agonist responses at the rat orthologue (rTRPM8 IC50 (menthol) = 117 ± 18 nM, IC50 (icilin) = 521 ± 20 nM). Whole-cell patch-clamp recordings of hTRPM8 confirm the 1 inhibition of menthol-stimulated currents, with an IC50 of 700 ± 200 nM. We demonstrate that 1 possesses ≥400-fold selectivity for hTRPM8 versus hTRPA1/hTRPV1. (−)-menthyl 1 can be used as a novel chemical tool to study hTRPM8 pharmacology and differences in species commonly used in drug discovery.
https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00001
Transient receptor potential melastatin 8 (trpm8) antagonists and related methods
Journigan VB. WO 2020160464 A1.
A TRPM8 antagonist is provided that comprises the following the formula (I) described herein. In the formula (I), R1 is selected from a cycloalkyl, a bicycloalkyl, or a tricycloalkyl group. Each R1 group has 5 to 12 carbon atoms. Further, each R1 group is optionally substituted with an alkyl group having 1 to 5 carbons atoms or with a cycloalkyl group having 4 to 12 carbon atoms, and each R1 group is optionally saturated or partially unsaturated. Methods for treating pain are further provided and comprise administering to a subject in need thereof an effective amount of a TRPM8 antagonist comprising the formula (I).
https://ie.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_IE&FT=D&date=20200806&CC=WO&NR=2020160464A1&KC=A1
Engaging the Medicinal Chemists of Tomorrow
Ferrins et al, J Med Chem 2022
The Young Medicinal Chemists Committee (YMCC) is a part of the larger ACS Division of Medicinal Chemistry (MEDI) and was formed to ensure that MEDI meets the needs of all medicinal chemists, including students and early career scientists. There is a clear need to offer additional, specific opportunities to this group of medicinal chemists within the MEDI division. Primary functions of YMCC include facilitating networking and mentorship opportunities, collaborating with international medicinal chemistry societies, and offering social programming for all MEDI members at ACS National Meetings. We are excited to continue to engage students and early career chemists through new initiatives and programming in the future. In this Editorial we highlight current initiatives relevant to early career medicinal chemists and solicit input from the larger medicinal chemistry community.
https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c00424
Publicatons at pitt
Ferrins L, Araujo E, Boudreau MW, Grenier-Davies MC, Haranahalli K, Journigan VB, Klug DM, Olson ME. Engaging the Medicinal Chemists of Tomorrow. J Med Chem. 2022 May 12;65(9):6353-6355.
Publications at MU
Cooper, S.Y., Akers, A.T., Journigan, V.B., Henderson, B.J. Novel Putative Positive Modulators of α4β2 nAChRs Potentiate Nicotine Reward-Related Behavior. Molecules. 2021 Aug 7;26(16):4793. doi: 10.3390/molecules26164793. PMID: 34443380 PMCID: PMC8398432
Journigan, V.B.*, Alarcón-Alarcón, D., Feng, Z., Wang, Y., Liang, T., Dawley, D., Amin, A.R.M.R., Montano, C., Van Horn, W.D., Xie, X.-Q., Ferrer-Montiel, A., Fernández-Carvajal, A. Structural and in vitro functional characterization of a menthyl TRPM8 antagonist indicates species-dependent regulation. ACS Med Chem Lett. 2021 Mar 31;12(5):758-767. doi: 10.1021/acsmedchemlett.1c00001. PMID: 34055223 PMCID: PMC8155240 *corresponding author.
Journigan VB*, Feng Z, Rahman S, Wang Y, Amin ARMR, Heffner CE, Bachtel N, Wang S, Gonzalez-Rodriguez S, Fernández-Carvajal A, Fernández-Ballester G, Hilton JK, Van Horn WD, Ferrer-Montiel A, Xie X-Q, Rahman T. Structure-based design of novel biphenyl amide antagonists of human Transient Receptor Potential Cation Channel Subfamily M Member 8 channels (TRPM8) with potential implications in the treatment of sensory neuropathies. ACS Chem. Neurosci. 2020, 11, 268-290. PMID: 31850745, PMCID: PMC7153518. *corresponding author
Journigan VB. Marshall University Research Corporation, assignee. Transient Receptor Potential Melastatin 8 (TRPM8) antagonists and related methods. WO 2020160464 A1.
Publications prior to MU
Mottinelli M, Journigan VB, Obeng S, Pallares VLC, Mѐsangeau C, Kapanda CN, Cutler SJ, Lambert JA, Eans SO, Ganno ML, Sheng W, King T, Sharma A, Mollereau C, Avery BA, McLaughlin JP, McCurdy CR. Dual Opioid-Neuropeptide FF Small Molecule Ligands Demonstrate Analgesia with Reduced Tolerance Liabilities. Proc Natl Acad Sci U S A., submitted. equal author contribution.
Arcuri L, Novello S, Frassineti M, Mercatelli D, Pisanò CA, Morella I, Fasano S, Journigan BV, Meyer ME, Polgar WE, Brambilla R, Zaveri NT, Morari M. Anti-Parkinsonian and anti-dyskinetic profiles of two novel potent and selective nociceptin/orphanin FQ receptor agonists. Br J Pharmacol. 2018 Mar;175(5):782-796. doi: 10.1111/bph.14123. Epub 2018 Jan 31. PubMed PMID: 29232769; PubMed Central PMCID: PMC5811622.
Kallupi M, Shen Q, de Guglielmo G, Yasuda D, Journigan VB, Zaveri NT, Ciccocioppo R. Buprenorphine requires concomitant activation of NOP and MOP receptors to reduce cocaine consumption. Addict Biol. 2018 Mar;23(2):585-595. doi: 10.1111/adb.12513. Epub 2017 Jun 21. PubMed PMID: 28635181; PubMed Central PMCID: PMC5740020.
Journigan VB, Polgar WE, Tuan EW, Lu J, Daga PR, Zaveri NT. Probing ligand recognition of the opioid pan antagonist AT-076 at nociceptin, kappa, mu, and delta opioid receptors through structure-activity relationships. Sci Rep. 2017 Oct 16;7(1):13255. doi: 10.1038/s41598-017-13129-1. PubMed PMID: 29038479; PubMed Central PMCID: PMC5643385.
Ferrari F, Malfacini D, Journigan BV, Bird MF, Trapella C, Guerrini R, Lambert DG, Calo' G, Zaveri NT. In vitro pharmacological characterization of a novel unbiased NOP receptor-selective nonpeptide agonist AT-403. Pharmacol Res Perspect. 2017 Aug;5(4). doi: 10.1002/prp2.333. PubMed PMID: 28805972; PubMed Central PMCID: PMC5684865.
Zaveri NT, Meyer M, Journigan VB, Yasuda D; Astraea Therapeutics, LLC, assignee.Preparation of piperidinyl-containing nociceptin receptor ligand compounds. WO 2017096323; US20180155314 A1
Ferrari F, Cerlesi MC, Malfacini D, Asth L, Gavioli EC, Journigan BV, Kamakolanu UG, Meyer ME, Yasuda D, Polgar WE, Rizzi A, Guerrini R, Ruzza C, Zaveri NT, Calo G. In vitro functional characterization of novel nociceptin/orphanin FQ receptor agonists in recombinant and native preparations. Eur J Pharmacol. 2016 Dec 15;793:1-13. doi: 10.1016/j.ejphar.2016.10.025. Epub 2016 Oct 22. PubMed PMID: 27780725; PubMed Central PMCID: PMC5555400.
Zaveri NT, Journigan VB, Polgar WE. Discovery of the first small-molecule opioid pan antagonist with nanomolar affinity at mu, delta, kappa, and nociceptin opioid receptors. ACS Chem Neurosci. 2015 Apr 15;6(4):646-57. doi: 10.1021/cn500367b. Epub 2015 Feb 18. PubMed PMID: 25635572; PubMed Central PMCID: PMC4401318.
Journigan VB, Mésangeau C, Vyas N, Eans SO, Cutler SJ, McLaughlin JP, Mollereau C, McCurdy CR. Nonpeptide small molecule agonist and antagonist original leads for neuropeptide FF1 and FF2 receptors. J Med Chem. 2014 Nov 13;57(21):8903-27. doi: 10.1021/jm500989n. Epub 2014 Oct 21. PubMed PMID: 25268943; PubMed Central PMCID: PMC4234442.
Journigan VB, Polgar WE, Khroyan TV, Zaveri NT. Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP-receptor selective scaffolds. Part II. Bioorg Med Chem. 2014 Apr 15;22(8):2508-16. doi: 10.1016/j.bmc.2014.02.047. Epub 2014 Mar 5. PubMed PMID: 24657054; PubMed Central PMCID: PMC4033624.
Journigan VB, Zaveri NT. TRPM8 ion channel ligands for new therapeutic applications and as probes to study menthol pharmacology. Life Sci. 2013 Mar 19;92(8-9):425-37. doi: 10.1016/j.lfs.2012.10.032. Epub 2012 Nov 16. Review. PubMed PMID: 23159643.
Zaveri NT, Yasuda D, Journigan BV, Daga PR, Jiang F, Olsen C. Structure-Activity Relationships of Nociceptin Receptor (NOP) Ligands and the Design of Bifunctional NOP/Mu Opioid Receptor-Targeted Ligands . In: ACS Symposium Series. Washington, DC: American Chemical Society; 2013. Chapter 8; p.145–160.
Gregory SM, Cavenaugh A, Journigan V, Pokorny A, Almeida PF. A quantitative model for the all-or-none permeabilization of phospholipid vesicles by the antimicrobial peptide cecropin A. Biophys J. 2008 Mar 1;94(5):1667-80. doi: 10.1529/biophysj.107.118760. Epub 2007 Oct 5. PubMed PMID: 17921201; PubMed Central PMCID: PMC2242756.