Molecular Formula | C22H22N4O4 |
Molar Mass | 406.43 |
Density | 1.328 |
Storage Condition | -20℃ |
In vitro study | BMS-806 is a 7-azaindole derivative that binds to gp120 and interferes with the interaction of the HIV surface protein gp120 with the host cell receptor CD4. BMS-806 inhibits a panel of macrophage and T-cell thermophilic HIV-1 strains, an experimental strain that uses CCR5(M-thermophilic) or CXR4(T-thermophilic) co-receptors, into the cell, divided into B subtype. The aqueous solubility of the BMS-806 crystalline form (BMS 378806) was 170 μg/mL. At pH 2.1 and 11, the solubility of BMS-806 is 1.3 mg/mL and 3.3 mg/mL respectively. The dissolution spectrum shows the Amphoteric nature of BMS-806, and it can be estimated that the protonated form has a pK a of 2.9, while the free base has a pK a of 9.6. In the ELISA assay, BMS-806 and soluble CD4 competitively bind to the gp120 monomeric form with IC50 = -100 nM. BMS-806 at concentrations of 10 to 30 μm specifically acts on HIV-1 and has no significant inhibitory activity against HIV-2, SIV, MuLV, RSV, HCMV, BVDV, VSV, and influenza viruses, there was also no significant toxicity to host cells, CC50> 225 μm. BMS-806 binds directly to gp120 with a stoichiometry of 1:1, similar to the binding affinity of soluble CD4. By using HIV-1 gp120 variants carrying anti-compound selective surrogates or gp120-CD4 contact point mutations, potential targets of BMS-806 are localized to specific regions of the CD4 binding pocket of gp120. |
In vivo study | BMS-806 treatment of AUC was increased in proportion to the dose, C max was observed. In rats, dogs, monkeys, the plasma concentration of the drug exceeds the concentration required for half-maximal inhibition of viral replication in vitro. The volume of distribution of BMS-806 was 0.4 to 0.6 L/kg, indicating a higher volume than plasma, whereas brain level measurements in rats showed minimal CNS penetration. BMS-806 acts on human, rat, dog, and monkey blood, 37 |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.46 ml | 12.302 ml | 24.604 ml |
5 mM | 0.492 ml | 2.46 ml | 4.921 ml |
10 mM | 0.246 ml | 1.23 ml | 2.46 ml |
5 mM | 0.049 ml | 0.246 ml | 0.492 ml |