Biological Activity
yya-021 is a small-molecule cd4 mimic that inhibits hiv entry [1].cd4 is a cell surface protein. the entry of human immunodeficiency virus type 1 (hiv-1) into target cells is initiated by the interaction of cd4 and viral envelope glycoprotein gp120. cd4 mimic inhibits the interaction between gp120 and cd4 and then inhibits hiv entry [1].yya-021 is a small-molecule cd4 mimic that inhibits hiv entry. yya-021 competitively inhibited gp120-cd4 interaction [1]. in tzm-bl cells infected with simian-human immunodeficiency virus isolate mna (shiv mna) or hiv-1 mna pseudotyped viruses, yya-021 inhibited the entry of envs of shiv mna and hiv-1. kd-247 (the anti-v3 loop mab, 50 μg) caused 50% neutralization of hiv-1 mna. however, in the presence of 20 μm of yya-021, kd-247 (<0.05 μg) caused 50% neutralization of hiv-1 mna, which suggested that the synergistic neutralization effect of yya-021 and kd-247. in the presence of yya-021, shiv mna became more sensitive to igg [2].in jcl:sd rats, the maximum tolerated dose of yya-021.hcl was 2.5 mg. when administrated by tail vein injection, yya-021 exhibited widespread tissue distribution due to its hydrophobicity. in a rhesus macaque, the maximum tolerated dose of yya-021.hcl was 35.3 mg [1].
References
[1]. hashimoto c, narumi t, otsuki h, et al. a cd4 mimic as an hiv entry inhibitor: pharmacokinetics. bioorg med chem, 2013, 21(24): 7884-7889.
[2]. otsuki h, hishiki t, miura t, et al. generation of a replication-competent simian-human immunodeficiency virus, the neutralization sensitivity of which can be enhanced in the presence of a small-molecule cd4 mimic. j gen virol, 2013, 94(pt 12): 2710-2716.
