|IUPAC Name:||[(2S)-1-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxypropan-2-yl]oxymethyl-(3-hexadecoxypropoxy)phosphinic acid|
CMX001 (Brincidofovir; HDP-CDV) was developed as an orally active, lipophilic form of cidofovir (CDV); has enhanced activity in vitro and in vivo compared to CDV against certain herpesviruses, adenoviruses and orthopoxviruses.
IC50 Value: 5.5 nM (EC50, in PDA at 7 dpi) 
CMX001 is currently in Phase II clinical studies for development as a therapeutic agent for human CMV, adenovirus and BK virus infections, as well as, for adverse events following smallpox vaccinations.
in vitro: In PDA at 7 dpi, the CMX001 50% effective concentration (EC50) was 5.55 nM, the 50% cytotoxic concentration (CC50) was 184.6 nM, and the 50% selectivity index (SI50) was 33.3. The EC90 was 19.7 nM, the CC90 was 5,054 nM, and the SI90 was 256.1. In COS-7 cells, JCV replication was faster and the EC50 and EC90 were 18- and 37-fold higher than those in PDA, i.e., 0.1 μM and 0.74 μM (CC50, 0.67 μM; SI50, 6.7; CC90, 12.2 μM; SI90, 16.5) at 5 dpi .
in vivo: CMX001 and CDV are equally efficacious at protecting mice from mortality following high ectromelia virus doses (10,000 x LD(50)) introduced by the intra-nasal route or small particle aerosol. Using CMX001 at a 10mg/kg dose followed by 2.5mg/kg doses every other-day for 14 days provided solid protection against mortality and weight loss following an intra-nasal challenge of (100-200) x LD(50) of ectromelia virus . When CMX001 was administered orally to mice infected with HSV-1, mortality was reduced significantly (p≤0.001) with all three dose levels when treatments were initiated 24 h post viral inoculation. When treatments were started 48 h post viral inoculation, 5 and 2.5 mg/kg significantly reduced mortality (p≤ 0.001). If treatments were delayed until 72 h post viral inoculation, CMX001 did not reduce mortality or increase the mean day to death. When mice were infected intranasally with HSV-1 and treatments initiated 24 h post viral inoculation using CMX001 at 5 mg/kg or ACV at 100 mg/kg, virus replication in target organs was reduced by both CMX001 and ACV when compared to vehicle treated mice .
Toxicity: Diarrhea was the most common adverse event in patients receiving CMX001 at doses of 200 mg weekly or higher and was dose-limiting at 200 mg twice weekly. Myelosuppression and nephrotoxicity were not observed .
1:Brincidofovir (CMX001) inhibits BK polyomavirus replication in primary human urothelial cells. Tylden GD, Hirsch HH, Rinaldo CH.Antimicrob Agents Chemother. 2015;59(6):3306-16. doi: 10.1128/AAC.00238-15. Epub 2015 Mar 23. PMID: 25801568 Free PMC Article
2:Treatment of BK virus-associated nephropathy with CMX001 after kidney transplantation in a young child. Reisman L, Habib S, McClure GB, Latiolais LS, Vanchiere JA.Pediatr Transplant. 2014 Nov;18(7):E227-31. doi: 10.1111/petr.12340. Epub 2014 Aug 30. PMID: 25174393
3:Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus. Parker S, Crump R, Foster S, Hartzler H, Hembrador E, Lanier ER, Painter G, Schriewer J, Trost LC, Buller RM.Antiviral Res. 2014 Nov;111:42-52. doi: 10.1016/j.antiviral.2014.08.003. Epub 2014 Aug 13. PMID: 25128688
4:Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses. Florescu DF, Keck MA.Expert Rev Anti Infect Ther. 2014 Oct;12(10):1171-8. doi: 10.1586/14787210.2014.948847. Epub 2014 Aug 13. PMID: 25120093
5:CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, Brundage TM, Robertson AT, Godkin S, Momméja-Marin H, Boeckh M; CMX001-201 Clinical Study Group..N Engl J Med. 2013 Sep 26;369(13):1227-36. doi: 10.1056/NEJMoa1303688. PMID: 24066743 Free Article
6:Selection and recombinant phenotyping of a novel CMX001 and cidofovir resistance mutation in human cytomegalovirus. James SH, Price NB, Hartline CB, Lanier ER, Prichard MN.Antimicrob Agents Chemother. 2013 Jul;57(7):3321-5. doi: 10.1128/AAC.00062-13. Epub 2013 May 6. PMID: 23650158 Free PMC Article
7:Progressive vaccinia: case description and laboratory-guided therapy with vaccinia immune globulin, ST-246, and CMX001. Lederman ER, Davidson W, Groff HL, Smith SK, Warkentien T, Li Y, Wilkins KA, Karem KL, Akondy RS, Ahmed R, Frace M, Shieh WJ, Zaki S, Hruby DE, Painter WP, Bergman KL, Cohen JI, Damon IK.J Infect Dis. 2012 Nov;206(9):1372-85. doi: 10.1093/infdis/jis510. Epub 2012 Aug 16. PMID: 22904336 Free PMC Article
8:First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Painter W, Robertson A, Trost LC, Godkin S, Lampert B, Painter G.Antimicrob Agents Chemother. 2012 May;56(5):2726-34. doi: 10.1128/AAC.05983-11. Epub 2012 Mar 5. PMID: 22391537 Free PMC Article
9:Treatment of Vaccinia and Cowpox Virus Infections in Mice with CMX001 and ST-246. Quenelle DC, Kern ER.Viruses. 2010 Dec;2(12):2681-95. doi: 10.3390/v2122681. Epub 2010 Dec 13. PMID: 21994637 Free PMC Article
10:Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients. Florescu DF, Pergam SA, Neely MN, Qiu F, Johnston C, Way S, Sande J, Lewinsohn DA, Guzman-Cottrill JA, Graham ML, Papanicolaou G, Kurtzberg J, Rigdon J, Painter W, Mommeja-Marin H, Lanier R, Anderson M, van der Horst C.Biol Blood Marrow Transplant. 2012 May;18(5):731-8. doi: 10.1016/j.bbmt.2011.09.007. Epub 2011 Sep 29. PMID: 21963623 Free PMC Article