CMX001 (Synonyms: Brincidofovir; HDP-CDV)

CMX001 is a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV) used for treatment of smallpox.^[1]

In vitro experiment it shown that 0.079 µM CMX001 inhibited JCV replication in COS-7 cells. And treatment with 0.038 µM or 0.6 µM CMX001 in PDA cells resulted in a obviously decreased the number of infectious JCV progeny in a concentration-dependent manner. Treatment with 0.079 to 10 µM CMX001 in COS-7 cells reduced the metabolic activity to 52% and BrdU incorporation to 10% at the highest concentration.^[2] CMX001 was active with EC90 of 0.31 µM at about 400-times-lower concentrations than the EC90 for CDV in the same test system.^[3] In vitro efficacy test it exhibited that treatment with 0.01 µM to 0.1 µM resulted in minimal cytotoxic effects in human fetal brain SVG cells.^[4] In vitro, CMX001 has against five variola virus strains with EC50 of averaged 0.11 µM.^[5]

In vivo clinical study it shown that treatment with oral CMX001 at a dose of 100 mg twice weekly obviously reduced the incidence of CMV events in recipients of hematopoietic-cell transplants.^[6] In ECTV-infected A/NCR mice, a 2.5 mg/kg dose of CMX001 given once daily for five days starting 4 h post-infection provides complete protection against a lethal intranasal challenge. Mice were treated with 10 mg/kg CMX001 when the fifth day, then followed by a 2.5 mg/kg dose every other day for 14 days can be completely protected from mortality. However, treatment with 20 mg/kg CMX001 orally as late as four days post-infection provided 100% protection against lethal ECTV infection.^[7]

References:

[1].Rice AD, et al. Efficacy of CMX001 as a post exposure antiviral in New Zealand White rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans. Viruses. 2011 Jan;3(1):47-62.

[2].Gosert R, et al. CMX001 (1-O-hexadecyloxypropyl-cidofovir) inhibits polyomavirus JC replication in human brain progenitor-derived astrocytes. Antimicrob Agents Chemother. 2011 May;55(5):2129-36.

[3].Rinaldo CH, et al. 1-O-hexadecyloxypropyl cidofovir (CMX001) effectively inhibits polyomavirus BK replication in primary human renal tubular epithelial cells. Antimicrob Agents Chemother. 2010 Nov;54(11):4714-22.

[4].Jiang ZG, et al. Hexadecyloxypropyl-cidofovir (CMX001) suppresses JC virus replication in human fetal brain SVG cell cultures. Antimicrob Agents Chemother. 2010 Nov;54(11):4723-32.

[5].Olson VA, et al. In vitro efficacy of brincidofovir against variola virus. Antimicrob Agents Chemother. 2014 Sep;58(9):5570-1.

[6].Marty FM, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013 Sep 26;369(13):1227-36.

[7].Lanier R, et al. Development of CMX001 for the Treatment of Poxvirus Infections. Viruses. 2010 Dec;2(12):2740-2762.