Representative Publications
Structure based design
- Structure-based design of bitopic ligands for the µ-opioid receptor.
Faouzi, A., Wang, H., Zaidi, S.A., DiBerto, J.F., Che,T., Qu, Q., Robertson, M.J., Madasu, M., El Daibani, A., Varga, B.R., Zhang, T., Ruiz, C., Liu, S., Xu, J., Appourchaux, K., Slocum, S.T., Eans, S.O., Cameron, M.D., Al-Hasani, R., Pan, Y.X., Roth, B.L., McLaughlin, J.P., Skiniotis*, G., Katritch*, V., Kobilka* ,B.K., and Majumdar S.* Structure-based design of functionally selective bitopic ligands for the µ-opioid receptor. Nature 2023, 613(7945):767-774.
- Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site Uprety, R., Che, T., Zaidi, S.A., Grinnell, S.G., Varga, B.R., Faouzi, A., Slocum, S.T., Allaoa, A., Varadi, A., Nelson, M., Bernhard. S.M., Kulko, E., Le Rouzic, V., Eans, S.O., Simons, C.A., Hunkele, A., Subrath, J., Pan, Y.X., Javitch, J.A., McLaughlin, J.P., Roth, B.L., Pasternak, G.W., Katritch, V. and Majumdar S. Elife 2021, 10:e56519.
- Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor. T, Majumdar S, Zaidi SA, Ondachi P, McCorvy JD, Wang S, Mosier PD, Uprety R, Vardy E, Krumm BE, Han GW, Lee MY, Pardon E, Steyaert J, Huang XP, Strachan RT, Tribo AR, Pasternak GW, Carroll FI, Stevens RC, Cherezov V, Katritch V, Wacker D, Roth BL. Cell 2018;172(1-2):55-67.e15.
Morphinans
- MP1104, a mixed kappa-delta opioid receptor agonist has anti-cocaine properties with reduced side-effects in rats.
Atigari DV, Uprety R, Pasternak GW, Majumdar S, Kivell BM. Neuropharmacology. 2019. pii: S0028-3908(18)30757-3.
- Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior.
Váradi A, Marrone GF, Eans SO, Ganno ML, Subrath JJ, Le Rouzic V, Hunkele A, Pasternak GW, McLaughlin JP, Majumdar S.
ACS Chem Neurosci. 2015;6(11):1813-24.
- Novel 6β-acylaminomorphinans with analgesic activity.
Váradi A, Hosztafi S, Le Rouzic V, Tóth G, Urai Á, Noszál B, Pasternak GW, Grinnell SG, Majumdar S.
Eur J Med Chem. 2013, 69:786-9.
- Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects.
Majumdar S, Grinnell S, Le Rouzic V, Burgman M, Polikar L, Ansonoff M, Pintar J, Pan YX, Pasternak GW.
Proc Natl Acad Sci U S A. 2011;108(49):19778-83.
Mitragynine(s)
- A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects.
Chakraborty, S., Diberto, J.F., Faouzi, A., Bernhard, S.M., Gutridge, A.M., Ramsey, S., Zhou, Y., Provasi, D., Nuthikattu, N., Jilakara, R., Nelson, M.N.F., Asher, W.B., Eans, S.O., Wilson, L.L., Chintala, S.M., Filizola, M., van Rijn, R.M., Margolis, E.B., Roth, B.L., McALughlin, J.P., Che, T., Sames, D., Javitch, J.A. and Majumdar, S.
J Med Chem 2021,64(18),13873-13892.
- Insights into distinct signaling profiles of the µOR activated by diverse agonists. Qu,Q.,Huang,W., Aydin,D., Paggi,J.M.,Seven, A.B.,Wang,H.,Chakraborty, S.,Che,T.,Diberto, J.F., Robertson, J.F., Inoue, A., Roth, B.L., Majumdar S.,* Dror, R.O.,* Kobilka, B.K.,* and Skinitiotis, G.* Nature Chemical Biology 2022, 19(4):423-430.
- Kratom Alkaloids as Probes for Opioid Receptor Function: Pharmacological Characterization of Minor Indole and Oxindole Alkaloids from Kratom.Chakraborty, S., Uprety, R., Daibani, A.E., Rouzic. VL., Hunkele, A., Appourchaux, K., Eans, S.O., Nuthikattu, N., Jilakara, R., Thammavong, L., Pasternak, G.W., Pan, Y.X., McLaughlin, J.P., Che, T., Majumdar, S. ACS Chem Neurosci. 2021,12(14), 2661-2678.
- 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects. Kruegel, A., Uprety, R., Grinnell, S., Langreck, S., Pekarskaya, E., Le Rouzic, V., Ansonoff, M., Gassaway, M., Pintar, J.E., Pasternak, G.W., Javitch, J., Majumdar, S. and Sames, D. ACS Central Sci. 2019, 5(6), 992-1001.
- Strategy for making safer opioids bolstered. Majumdar S, Devi LA. Nature. 2018 Jan 18;553(7688):286-288.
- Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2. Váradi A, Marrone GF, Palmer TC, Narayan A, Szabó MR, Le Rouzic V, Grinnell SG, Subrath JJ, Warner E, Kalra S, Hunkele A, Pagirsky J, Eans SO, Medina JM, Xu J, Pan YX, Borics A, Pasternak GW, McLaughlin JP, Majumdar S. J Med Chem. 2016;59(18):8381-97.
Fentanyl and MCRs
- Synthesis and Pharmacology of a Novel μ-δ Opioid Receptor Heteromer-Selective Agonist Based on the Carfentanyl Template.
Faouzi, A., Uprety, R., Gomes, I., Massaly, N., Keresztes, A.I., Le Rouzic, V., Gupta, A., Zhang, T., Yoon, H.J., Ansonoff, M., Allaoa, A., Pan, Y.X., Pintar, J., Morón, J.A., Streicher, J.M., Devi, L.A. and Majumdar S. J Med Chem. 2020;63(22):13618-13637
- Synthesis of spiro-2,6-dioxopiperazine and spiro-2,6-dioxopyrazine scaffolds using amino acids in a three-component reaction to generate potential Sigma-1 (σ1) receptor selective ligands.
Uprety R, Váradi A, Allaoa A, Redel-Traub GN, Palmer TC, Feinberg EN, Ferris AC, Pande VS, Pasternak GW, Majumdar S. Eur J Med Chem. 2019;164:241-251
- Pharmacological characterization of novel synthetic opioids (NSO) found in the recreational drug marketplace.
Baumann MH, Majumdar S,, Le Rouzic V, Hunkele A, Uprety R, Huang XP, Xu J, Roth BL, Pan YX, Pasternak GW. Neuropharmacology. 2018 May 15;134(Pt A):101-107.
- Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles.
Váradi A, Palmer TC, Notis Dardashti R, Majumdar S. Molecules. 2015;21(1):E19.
- Synthesis of Carfentanil Amide Opioids Using the Ugi Multicomponent Reaction.
Váradi A, Palmer TC, Haselton N, Afonin D, Subrath JJ, Le Rouzic V, Hunkele A, Pasternak GW, Marrone GF, Borics A, Majumdar S. ACS Chem Neurosci. 2015;6(9):1570-7.
- Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles.
Váradi A, Palmer TC, Notis Dardashti R, Majumdar S. Molecules. 2015;21(1):E19.
- Three-component coupling approach for the synthesis of diverse heterocycles utilizing reactive nitrilium trapping.
Váradi A, Palmer TC, Notis PR, Redel-Traub GN, Afonin D, Subrath JJ, Pasternak GW, Hu C, Sharma I, Majumdar S. Org Lett. 2014;16(6):1668-71.