Censavudine

Censavudine (OBP-601; BMS-986001), a nucleoside analog, is a nucleoside reverse transcriptase inhibitor. Censavudine is a potent HIV inhibitor with EC₅₀ ranges from 30 nM to 81 nM and 450 nM to 890 nM for HIV-2 and HIV-1, respectively^[1][2]. Censavudine is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. In Vitro: BMS-986001 shows greater activity against HIV-2_ROD9 than against HIV-1_NL4-3; the mean EC₅₀s for BMS-986001 are 74 nM for HIV-2_ROD9 and 890 nM for HIV-1_NL4-3 in the single-cycle assay. HIV-2_ROD9 also showes greater sensitivity to BMS-986001 in 4-day infections of an immortalized T cell line (CEMss), with the mean EC₅₀ for HIV-2_ROD9 (EC₅₀ of 0.14 nM) being 30-fold lower than that for HIV-1_NL4-3 (EC₅₀ of 4.2 nM)^[1].
BMS-986001 also exhibits full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase^[1]. In Vivo: The pharmacokinetic parameters of Censavudine (BMS-986001; 100-750 mg/kg) generated from the dried blood spot (DBS) assay and the plasma assay is compared. The ratios of the AUC_{(0-24 h)} and C _max for BMS-986001 in DBS compared to those in plasma are consistent at 0.83-0.91 and 0.81-0.97, respectively, across all dose groups in rats. The T _max in rat DBS and plasma are also consistent at about 1 h^[2].