Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Phosphate Prodrugs: An Approach to Improve the Bioavailability of Clinically Approved Drugs

Author(s): Tanmoy Tantra, Yogesh Singh, Rohan Patekar, Swanand Kulkarni, Pradeep Kumar and Suresh Thareja*

Volume 31, Issue 3, 2024

Published on: 21 March, 2023

Page: [336 - 357] Pages: 22

DOI: 10.2174/0929867330666230209094738

Price: $65


The phosphate prodrug approach has emerged as a viable option for increasing the bioavailability of a drug candidate with low hydrophilicity and poor cell membrane permeability. When a phosphoric acid moiety is attached to the parent drug, it results in a several-fold elevation in aqueous solubility which helps to achieve desired bioavailability of the pharmaceutically active parental molecule. The neutral phosphate prodrugs have rapid diffusion ability through the plasma membrane as compared to their charged counterpart. The presence of phosphate mono ester breaking alkaline phosphatase (ALP) enzyme throughout the whole human body, is the main consideration behind the development of phosphate prodrug strategy. The popularity of this phosphate prodrug strategy is increasing nowadays due to the fulfillment of different desired pharmacokinetic characteristics required to get pharmaceutical and therapeutic responses without showing any serious adverse drug reactions (ADR). This review article mainly focuses on various phosphate prodrugs synthesized within the last decade to get an improved pharmacological response of the parent moiety along with various preclinical and clinical challenges associated with this approach. Emphasis is also given to the chemical mechanism to release the parent moiety from the prodrug.

Keywords: Phosphate, prodrug, solubility, pharmacokinetics, bioavailability, adverse drug reactions, pharmacodynamics, phosphoric acid.

Singh, Y.; Saklani, S.; Tantra, T.; Thareja, S. Amino acid derived prodrugs: An approach to improve the bioavailability of clinically approved drugs. Curr. Top. Med. Chem., 2021, 21(24), 2170-2183.
[] [PMID: 34080965]
Abet, V.; Filace, F.; Recio, J.; Alvarez-Builla, J.; Burgos, C. Prodrug approach: An overview of recent cases. Eur. J. Med. Chem., 2017, 127, 810-827.
[] [PMID: 27823878]
Singh, Y.; Palombo, M.; Sinko, P. Recent trends in targeted anticancer prodrug and conjugate design. Curr. Med. Chem., 2008, 15(18), 1802-1826.
[] [PMID: 18691040]
Schultz, C. Prodrugs of biologically active phosphate esters. Bioorg. Med. Chem., 2003, 11(6), 885-898.
[] [PMID: 12614874]
Krise, J.P.; Stella, V.J. Prodrugs of phosphates, phosphonates, and phosphinates. Adv. Drug Deliv. Rev., 1996, 19(2), 287-310.
Müller, C.E. Prodrug approaches for enhancing the bioavailability of drugs with low solubility. Chem. Biodivers., 2009, 6(11), 2071-2083.
[] [PMID: 19937841]
Redasani, V.K.; Bari, S.B. Prodrug Design: Perspectives, Approaches and Applications in Medicinal Chemistry; Academic Press: Massachusetts, USA, 2015.
Dal Corso, A.; Pignataro, L.; Belvisi, L.; Gennari, C. Innovative linker strategies for tumor-targeted drug conjugates. Chemistry, 2019, 25(65), 14740-14757.
[] [PMID: 31418970]
Kumpulainen, H.; Järvinen, T.; Mannila, A.; Leppänen, J.; Nevalainen, T.; Mäntylä, A.; Vepsäläinen, J.; Rautio, J. Synthesis, in vitro and in vivo characterization of novel ethyl dioxy phosphate prodrug of propofol. Eur. J. Pharm. Sci., 2008, 34(2-3), 110-117.
[] [PMID: 18403185]
Vale, N.; Ferreira, A.; Matos, J.; Fresco, P.; Gouveia, M. Amino acids in the development of prodrugs. Molecules, 2018, 23(9), 2318.
[] [PMID: 30208629]
N’Da, D. Prodrug strategies for enhancing the percutaneous absorption of drugs. Molecules, 2014, 19(12), 20780-20807.
[] [PMID: 25514222]
Rautio, J.; Kumpulainen, H.; Heimbach, T.; Oliyai, R.; Oh, D.; Järvinen, T.; Savolainen, J. Prodrugs: design and clinical applications. Nat. Rev. Drug Discov., 2008, 7(3), 255-270.
[] [PMID: 18219308]
Shirke, S.; Shewale, S.; Satpute, M. Prodrug design: an overview. Int. J. Pharm. Chem. Biol. Sci., 2015, 5(1), 232-241.
Hajnal, K.; Gabriel, H.; Aura, R.; Erzsébet, V.; Blanka, S.S. Prodrug strategy in drug development. Acta Med. Marisiensis, 2016, 62(3), 356-362.
Huttunen, K.M.; Raunio, H.; Rautio, J. Prodrugs--from serendipity to rational design. Pharmacol. Rev., 2011, 63(3), 750-771.
[] [PMID: 21737530]
DeGoey, D.A.; Grampovnik, D.J.; Flosi, W.J.; Marsh, K.C.; Wang, X.C.; Klein, L.L.; McDaniel, K.F.; Liu, Y.; Long, M.A.; Kati, W.M.; Molla, A.; Kempf, D.J. Water-soluble prodrugs of the human immunodeficiency virus protease inhibitors lopinavir and ritonavir. J. Med. Chem., 2009, 52(9), 2964-2970.
[] [PMID: 19348416]
A M Subbaiah, M.; Mandlekar, S.; Desikan, S.; Ramar, T.; Subramani, L.; Annadurai, M.; Desai, S.D.; Sinha, S.; Jenkins, S.M.; Krystal, M.R.; Subramanian, M.; Sridhar, S.; Padmanabhan, S.; Bhutani, P.; Arla, R.; Singh, S.; Sinha, J.; Thakur, M.; Kadow, J.F.; Mean-well, N.A.M; Mandlekar, S.; Desikan, S.; Ramar, T.; Subramani, L.; Annadurai, M.; Desai, S.D.; Sinha, S.; Jenkins, S.M.; Krystal, M.R. Design, synthesis, and pharmacokinetic evaluation of phosphate and amino acid ester prodrugs for improving the oral bioavailability of the HIV-1 protease inhibitor atazanavir. J. Med. Chem., 2019, 62(7), 3553-3574.
[] [PMID: 30938524]
Fechner, J.; Schwilden, H.; Schüttler, J. Pharmacokinetics and pharmacodynamics of GPI 15715 or fospropofol (Aquavan injection)—a water-soluble propofol prodrug; Modern Anesthetics, 2008, pp. 253-266.
Stella, V.J.; Nti-Addae, K.W. Prodrug strategies to overcome poor water solubility. Adv. Drug Deliv. Rev., 2007, 59(7), 677-694.
[] [PMID: 17628203]
Sauer, R.; Maurinsh, J.; Reith, U.; Fülle, F.; Klotz, K.N.; Müller, C.E. Water-soluble phosphate prodrugs of 1-propargyl-8-styrylxanthine derivatives, A(2A)-selective adenosine receptor antagonists. J. Med. Chem., 2000, 43(3), 440-448.
[] [PMID: 10669571]
Takeda, E.; Taketani, Y.; Sawada, N.; Sato, T.; Yamamoto, H. The regulation and function of phosphate in the human body. Biofactors, 2004, 21(1-4), 345-355.
[] [PMID: 15630224]
Penido, M.G.M.G.; Alon, U.S. Phosphate homeostasis and its role in bone health. Pediatr. Nephrol., 2012, 27(11), 2039-2048.
[] [PMID: 22552885]
Wagner, C.A.; Hernando, N.; Forster, I.C.; Biber, J. The SLC34 family of sodium-dependent phosphate transporters. Pflugers Arch., 2014, 466(1), 139-153.
[] [PMID: 24352629]
Tsai, J.Y.; Chu, C.H.; Lin, M.G.; Chou, Y.H.; Hong, R.Y.; Yen, C.Y.; Hsiao, C.D.; Sun, Y.J. Structure of the sodium-dependent phosphate transporter reveals insights into human solute carrier SLC20. Sci. Adv., 2020, 6(32), eabb4024.
[] [PMID: 32821837]
Heimbach, T.; Oh, D-M.; Li, L.Y.; Forsberg, M.; Savolainen, J.; Leppänen, J.; Matsunaga, Y.; Flynn, G.; Fleisher, D. Absorption rate limit considerations for oral phosphate prodrugs. Pharm. Res., 2003, 20(6), 848-856.
[] [PMID: 12817887]
Le-Vinh, B.; Akkuş-Dağdeviren, Z.B.; Le, N.M.N.; Nazir, I.; Bernkop-Schnürch, A. Alkaline Phosphatase: A reliable endogenous partner for drug delivery and diagnostics. Adv. Ther. (Weinh.), 2022, 5(2), 2100219.
Ramalingam, M.; Kim, H.; Lee, Y.; Lee, Y.I. Phytochemical and pharmacological role of liquiritigenin and isoliquiritigenin from Radix glycyrrhizae in human health and disease models. Front. Aging Neurosci., 2018, 10, 348.
[] [PMID: 30443212]
Peng, F.; Du, Q.; Peng, C.; Wang, N.; Tang, H.; Xie, X.; Shen, J.; Chen, J. A review: the pharmacology of isoliquiritigenin. Phytother. Res., 2015, 29(7), 969-977.
[] [PMID: 25907962]
Traboulsi, H.; Cloutier, A.; Boyapelly, K.; Bonin, M.A.; Marsault, É.; Cantin, A.M.; Richter, M.V. The flavonoid isoliquiritigenin reduces lung inflammation and mouse morbidity during influenza virus infection. Antimicrob. Agents Chemother., 2015, 59(10), 6317-6327.
[] [PMID: 26248373]
Boyapelly, K.; Bonin, M.A.; Traboulsi, H.; Cloutier, A.; Phaneuf, S.C.; Fortin, D.; Cantin, A.M.; Richter, M.V.; Marsault, E. Synthesis and characterization of a phosphate prodrug of isoliquiritigenin. J. Nat. Prod., 2017, 80(4), 879-886.
[] [PMID: 28252963]
Wu, C.; Yan, J.; Li, W. Acacetin as a potential protective compound against cardiovascular diseases. Evid.-. Based Complement. Altern. Med., 2022, 2022, 6265198.
Liu, H.; Wang, Y.J.; Yang, L.; Zhou, M.; Jin, M.W.; Xiao, G.S.; Wang, Y.; Sun, H.Y.; Li, G.R. Synthesis of a highly water-soluble acacetin prodrug for treating experimental atrial fibrillation in beagle dogs. Sci. Rep., 2016, 6(1), 25743.
[] [PMID: 27160397]
Zhu, C.; Wang, R.; Zheng, W.; Chen, D.; Yue, X.; Cao, Y.; Qin, W.; Sun, H.; Wang, Y.; Liu, Z.; Li, B.; Du, J.; Bu, X.; Zhou, B. Synthesis and evaluation of anticancer activity of BOC26P, an ortho-aryl chalcone sodium phosphate as water-soluble prodrugs in vitro and in vivo. Biomed. Pharmacother., 2017, 96, 551-562.
[] [PMID: 29032339]
Sudhan, D.R.; Siemann, D.W. Cathepsin L targeting in cancer treatment. Pharmacol. Ther., 2015, 155, 105-116.
[] [PMID: 26299995]
Sudhan, D.R.; Siemann, D.W. Cathepsin L inhibition by the small molecule KGP94 suppresses tumor microenvironment enhanced metastasis associated cell functions of prostate and breast cancer cells. Clin. Exp. Metastasis, 2013, 30(7), 891-902.
[] [PMID: 23748470]
Parker, E.N.; Song, J.; Kishore Kumar, G.D.; Odutola, S.O.; Chavarria, G.E.; Charlton-Sevcik, A.K.; Strecker, T.E.; Barnes, A.L.; Sudhan, D.R.; Wittenborn, T.R.; Siemann, D.W.; Horsman, M.R.; Chaplin, D.J.; Trawick, M.L.; Pinney, K.G. Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L. Bioorg. Med. Chem., 2015, 23(21), 6974-6992.
[] [PMID: 26462052]
Parker, E.N.; Odutola, S.O.; Wang, Y.; Strecker, T.E.; Mukherjee, R.; Shi, Z.; Chaplin, D.J.; Trawick, M.L.; Pinney, K.G. Synthesis and biological evaluation of a water-soluble phosphate prodrug salt and structural analogues of KGP94, a lead inhibitor of cathepsin L. Bioorg. Med. Chem. Lett., 2017, 27(5), 1304-1310.
[] [PMID: 28117205]
Liu, Q. Triptolide and its expanding multiple pharmacological functions. Int. Immunopharmacol., 2011, 11(3), 377-383.
[] [PMID: 21255694]
Patil, S.; Lis, L.G.; Schumacher, R.J.; Norris, B.J.; Morgan, M.L.; Cuellar, R.A.D.; Blazar, B.R.; Suryanarayanan, R.; Gurvich, V.J.; Georg, G.I. Phosphonooxymethyl prodrug of triptolide: Synthesis, physicochemical characterization, and efficacy in human colon adenocarcinoma and ovarian cancer xenografts. J. Med. Chem., 2015, 58(23), 9334-9344.
[] [PMID: 26596892]
Dulac, M.; Sassi, A.; Nagarathinan, C.; Christen, M.O.; Dansette, P.M.; Mansuy, D.; Boucher, J.L. Metabolism of anethole dithiolethione by rat and human liver microsomes: formation of various products deriving from its O-demethylation and S-oxidation. Involvement of cytochromes P450 and flavin monooxygenases in these pathways. Drug Metab. Dispos., 2018, 46(10), 1390-1395.
[] [PMID: 30018103]
Chen, P.; Luo, Y.; Hai, L.; Qian, S.; Wu, Y. Design, synthesis, and pharmacological evaluation of the aqueous prodrugs of desmethyl anethole trithione with hepatoprotective activity. Eur. J. Med. Chem., 2010, 45(7), 3005-3010.
[] [PMID: 20392547]
Huang, S.; Dong, R.; Xu, G.; Liu, J.; Gao, X.; Yu, S.; Qie, P.; Gou, G.; Hu, M.; Wang, Y.; Peng, J.; Guang, B.; Xu, Y.; Yang, T. Synthesis, characterization, and in vivo evaluation of desmethyl anethole trithione phosphate prodrug for ameliorating cerebral ischemia-reperfusion injury in rats. ACS Omega, 2020, 5(9), 4595-4602.
[] [PMID: 32175506]
Zocchi, L.; Wu, S.C.; Wu, J.; Hayama, K.L.; Benavente, C.A. The cyclin-dependent kinase inhibitor flavopiridol (alvocidib) inhibits metastasis of human osteosarcoma cells. Oncotarget, 2018, 9(34), 23505-23518.
[] [PMID: 29805751]
Siddiqui-jain Adam. B.D.J. Alvocidib prodrugs having increased bioavailability. Patent no. WO2016187316, 2016.
George, B.; Richards, D.A.; Edenfield, W.J.; Warner, S.L.; Mouritsen, L.; Bishop, R.; Anthony, S.P.; Bearss, D.; Vogelzang, N.J.; Whatcott, C. A phase I, first-in-human, open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of oral TP-1287 administered daily to patients with advanced solid tumors. J. Clin. Oncol., 2020, 38(15), 3611.
Buckley, A.M.; Dunne, M.R.; Lynam-Lennon, N.; Kennedy, S.A.; Cannon, A.; Reynolds, A.L.; Maher, S.G.; Reynolds, J.V.; Kennedy, B.N.; O’Sullivan, J. Pyrazinib (P3), [(E)-2-(2-Pyrazin-2-yl-vinyl)-phenol], a small molecule pyrazine compound enhances radiosensitivity in oesophageal adenocarcinoma. Cancer Lett., 2019, 447, 115-129.
[] [PMID: 30664962]
McLoughlin, E.; Valupadasu, N.; O’Boyle, N.M. A phosphate prodrug of pyrazinib: Improved solubility and antiproliferative activity. 7th International Electronic Conference on Medicinal Chemistry Session Fighting Cancers, 1-30 November 2021MDPI: Basel, Switzerland.
Prasad, R.; Katiyar, S.K. Honokiol, an active compound of magnolia plant, inhibits growth, and progression of cancers of different organs. Adv. Exp. Med. Biol., 2016, 928, 245-265.
Arora, S.; Singh, S.; Piazza, G.A.; Contreras, C.M.; Panyam, J.; Singh, A.P. Honokiol: a novel natural agent for cancer prevention and therapy. Curr. Mol. Med., 2012, 12(10), 1244-1252.
[] [PMID: 22834827]
Xu, G.; Dong, R.; Liu, J.; Zhao, L.; Zeng, Y.; Xiao, X.; An, J.; Huang, S.; Zhong, Y.; Guang, B. Synthesis, characterization and in vivo evaluation of honokiol bisphosphate prodrugs protects against rats’ brain ischemia-reperfusion injury. Asian J. Pharmaceut. Sci., 2019, 14(6), 640-648.
Talley, A.K.; Thurston, A.; Moore, G.; Gupta, V.K.; Satterfield, M.; Manyak, E.; Stokes, S.; Dane, A.; Melnick, D. First-in-human evaluation of the safety, tolerability, and pharmacokinetics of SPR720, a novel oral bacterial DNA gyrase (GyrB) inhibitor for mycobacterial infections. Antimicrob. Agents Chemother., 2021, 65(11), e01208-21.
[] [PMID: 34491803]
Stokes, S.S.; Vemula, R.; Pucci, M.J. Advancement of GyrB inhibitors for treatment of infections caused by Mycobacterium tuberculosis and non-tuberculous mycobacteria. ACS Infect. Dis., 2020, 6(6), 1323-1331.
[] [PMID: 32183511]
Butler, M.S.; Gigante, V.; Sati, H.; Paulin, S.; Al-Sulaiman, L.; Rex, J.H.; Fernandes, P.; Arias, C.A.; Paul, M.; Thwaites, G.E.; Czaplewski, L.; Alm, R.A.; Lienhardt, C.; Spigelman, M.; Silver, L.L.; Ohmagari, N.; Kozlov, R.; Harbarth, S.; Beyer, P. Analysis of the clinical pipeline of treatments for drug-resistant bacterial infections: despite progress, more action is needed. Antimicrob. Agents Chemother., 2022, 66(3), e01991-21.
[] [PMID: 35007139]
Kumar, A.; Karkara, B.B.; Panda, G. Novel candidates in the clinical development pipeline for TB drug development and their synthetic approaches. Chem. Biol. Drug Des., 2021, 98(5), 787-827.
[] [PMID: 34397161]
Spero Therapeutics. Spero Therapeutics Announces Lifting of FDA Clinical Trial Hold on SPR720. Available from:
Tozer, G.M.; Kanthou, C.; Parkins, C.S.; Hill, S.A. The biology of the combretastatins as tumour vascular targeting agents. Int. J. Exp. Pathol., 2002, 83(1), 21-38.
[] [PMID: 12059907]
Garon, E.B.; Neidhart, J.D.; Gabrail, N.Y.; de Oliveira, M.R.; Balkissoon, J.; Kabbinavar, F. A randomized Phase II trial of the tumor vascular disrupting agent CA4P (fosbretabulin tromethamine) with carboplatin, paclitaxel, and bevacizumab in advanced nonsquamous non-small-cell lung cancer. OncoTargets Ther., 2016, 9, 7275-7283.
[] [PMID: 27942221]
Tron, G.C.; Pirali, T.; Sorba, G.; Pagliai, F.; Busacca, S.; Genazzani, A.A. Medicinal chemistry of combretastatin A4: present and future directions. J. Med. Chem., 2006, 49(11), 3033-3044.
[] [PMID: 16722619]
Zhang, C.; Zhang, X.; Wang, G.; Peng, Y.; Zhang, X.; Wu, H.; Yu, B.; Sun, J. Preclinical pharmacokinetics of C118P, a novel prodrug of microtubules inhibitor and its metabolite C118 in mice, rats, and dogs. Molecules, 2018, 23(11), 2883.
[] [PMID: 30400617]
Deeks, E.D. Venetoclax: first global approval. Drugs, 2016, 76(9), 979-987.
[] [PMID: 27260335]
Tresckow, J.V.; Eichhorst, B.; Bahlo, J.; Hallek, M. The treatment of chronic lymphatic leukemia. Dtsch. Arztebl. Int., 2019, 116(4), 41-46.
[PMID: 30855005]
Salem, A.H.; Tao, Z.F.; Bueno, O.F.; Chen, J.; Chen, S.; Edalji, R.; Elmore, S.W.; Fournier, K.M.; Harper, K.C.; Hong, R.; Jenkins, G.J.; Ji, J.; Judge, R.A.; Kalvass, J.C.; Klix, R.C.; Ku, Y.Y.; Leverson, J.D.; Marks, R.A.; Marsh, K.C.; Menon, R.M.; Park, C.H.; Phillips, D.C.; Pu, Y.M.; Rosenberg, S.H.; Sanzgiri, Y.D.; Sheikh, A.Y.; Shi, Y.; Stolarik, D.; Suleiman, A.A.; Wang, X.; Zhang, G.G.Z.; Catron, N.D.; Souers, A.J. Expanding the repertoire for “Large Small Molecules”: Prodrug ABBV-167 efficiently converts to venetoclax with reduced food effect in healthy volunteers. Mol. Cancer Ther., 2021, 20(6), 999-1008.
[] [PMID: 33785651]
Bristow, L.J.; Gulia, J.; Weed, M.R.; Srikumar, B.N.; Li, Y.W.; Graef, J.D.; Naidu, P.S.; Sanmathi, C.; Aher, J.; Bastia, T.; Paschapur, M.; Kalidindi, N.; Kumar, K.V.; Molski, T.; Pieschl, R.; Fernandes, A.; Brown, J.M.; Sivarao, D.V.; Newberry, K.; Bookbinder, M.; Polino, J.; Keavy, D.; Newton, A.; Shields, E.; Simmermacher, J.; Kempson, J.; Li, J.; Zhang, H.; Mathur, A.; Kallem, R.R.; Sinha, M.; Ramarao, M.; Vikramadithyan, R.K.; Thangathirupathy, S.; Warrier, J.; Islam, I.; Bronson, J.J.; Olson, R.E.; Macor, J.E.; Albright, C.F.; King, D.; Thompson, L.A.; Marcin, L.R.; Sinz, M. Preclinical characterization of (R)-3-((3S, 4S)-3-fluoro-4-(4-hydroxyphenyl) piperidin-1-yl)-1-(4-methylbenzyl) pyrrolidin-2-one (BMS-986169), a novel, intravenous, glutamate N-methyl-d-aspartate 2B receptor negative allosteric modulator with potential in major depressive disorder. J. Pharmacol. Exp. Ther., 2017, 363(3), 377-393.
[] [PMID: 28954811]
Marcin, L.R.; Warrier, J.; Thangathirupathy, S.; Shi, J.; Karageorge, G.N.; Pearce, B.C.; Ng, A.; Park, H.; Kempson, J.; Li, J.; Zhang, H.; Mathur, A.; Reddy, A.B.; Nagaraju, G.; Tonukunuru, G.; Gupta, G.V.R.K.M.; Kamble, M.; Mannoori, R.; Cheruku, S.; Jogi, S.; Gulia, J.; Bastia, T.; Sanmathi, C.; Aher, J.; Kallem, R.; Srikumar, B.N.; Vijaya, K.K.; Naidu, P.S.; Paschapur, M.; Kalidindi, N.; Vikramadithyan, R.; Ramarao, M.; Denton, R.; Molski, T.; Shields, E.; Subramanian, M.; Zhuo, X.; Nophsker, M.; Simmermacher, J.; Sinz, M.; Albright, C.; Bristow, L.J.; Islam, I.; Bronson, J.J.; Olson, R.E.; King, D.; Thompson, L.A.; Macor, J.E. BMS-986163, a negative allosteric modulator of GluN2B with potential utility in major depressive disorder. ACS Med. Chem. Lett., 2018, 9(5), 472-477.
[] [PMID: 29795762]
de Vries, M.; Mohamed, A.S.; Prescott, R.A.; Valero-Jimenez, A.M.; Ivanova, A.H.; Schinlever, A.; Loose, P.; Ruggles, K.; Sergei, B.; Koralov, A.S. A comparative analysis of SARS-CoV-2 antivirals in human airway models 1 characterizes 3CLpro inhibitor PF-00835231 as a potential new treatment for 2 COVID-19. J. Virol., 2021, 95(10), e01819-20.
Boras, B.; Jones, R.M.; Anson, B.J.; Arenson, D.; Aschenbrenner, L.; Bakowski, M.A.; Beutler, N.; Binder, J.; Chen, E.; Eng, H.; Hammond, H.; Hammond, J.; Haupt, R.E.; Hoffman, R.; Kadar, E.P.; Kania, R.; Kimoto, E.; Kirkpatrick, M.G.; Lanyon, L.; Lendy, E.K.; Lillis, J.R.; Logue, J.; Luthra, S.A.; Ma, C.; Mason, S.W.; McGrath, M.E.; Noell, S.; Obach, R.S.; O’ Brien, M.N.; O’Connor, R.; Ogilvie, K.; Owen, D.; Pettersson, M.; Reese, M.R.; Rogers, T.F.; Rosales, R.; Rossulek, M.I.; Sathish, J.G.; Shirai, N.; Steppan, C.; Ticehurst, M.; Updyke, L.W.; Weston, S.; Zhu, Y.; White, K.M.; García-Sastre, A.; Wang, J.; Chatterjee, A.K.; Mesecar, A.D.; Frieman, M.B.; Anderson, A.S.; Allerton, C. Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19. Nat. Commun., 2021, 12(1), 6055.
[] [PMID: 34663813]
Zhu, T.; Pawlak, S.; Toussi, S.S.; Hackman, F.; Thompson, K.; Song, W.; Salageanu, J.; Winter, E.; Shi, H.; Winton, J.; Binks, M. Safety, tolerability, and pharmacokinetics of intravenous doses of PF-07304814, a phosphate prodrug protease inhibitor for the treatment of SARS-CoV-2, in healthy adult participants. Clin. Pharmacol. Drug Dev., 2022, 11(12), 1382-1393.
[] [PMID: 36285536]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy