Structure-Based Discovery and Characterization of a Preclinical Drug Candidate for the Treatment of HIV-1 Infection.
Structure-Based Discovery and Characterization of a Preclinical Drug Candidate for the Treatment of HIV-1 Infection.
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基于结构的发现和表征治疗 HIV-1 感染的临床前候选药物
DOI：
10.3390/v14112390
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发表时间：
2022-10-28
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Kang D;Yang J;Kong L;Luo R;Huang X;Zhang T;Ma M;Feng D;Wang Z;Fang H;Zhan P;Zheng Y;Liu X
HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) area key component of the current HIV-1 combination drug regimens. Although they exhibit potent anti-HIV-1 activity and modest toxicity, the emergence of mutant strains limits their application in clinical. Our previous research efforts contributed to the identification of compound K-5a2, which exhibits nanomolar activity in HIV-1-infected MT-4 cells. In this study, K-5a2 was shown to have a high level of anti-HIV-1 activity against various lab-adapted strains and clinical isolate strains, being comparable to ETR. Moreover, we showed the feasibility of K-5a2 as a preclinical anti-HIV-1 candidate by establishing its synergistic or additive anti-HIV-1 activity in combination with other representative anti-HIV-1 drugs and candidates. In addition, K-5a2 exhibited no inhibitory activity to the primary CYP isoforms and favorable pharmacokinetics. Taken together, its robust anti-HIV-1 potency, synergistic or additive effects with other anti-HIV drugs, and favorable pharmacokinetic and safety profiles make K-5a2 a potent alternative drug for HIV/AIDS treatment.
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DOI：
10.2147/dddt.s65596
发表时间：
2014
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Cha YJ;Lim KS;Park MK;Schneider S;Bray B;Kang MC;Chung JY;Yoon SH;Cho JY;Yu KS
通讯作者：
Yu KS
影响因子：
3.1
作者：
PAUWELS, R;BALZARINI, J;DECLERCQ, E
通讯作者：
DECLERCQ, E
影响因子：
5.4
作者：
Vrancken, Bram;Zhao, Bin;Chaillon, Antoine
通讯作者：
Chaillon, Antoine
影响因子：
11.5
作者：
Al-Salama, Zaina T.
通讯作者：
Al-Salama, Zaina T.
DB-02 是一种具有纳摩尔活性的 C-6-环己基甲基取代的嘧啶酮 HIV-1 逆转录酶抑制剂，与 S-DABO 相比，对 K103N 或 Y181C 的敏感性更高
影响因子：
3.7
作者：
Zhang XJ;Lu LH;Wang RR;Wang YP;Luo RH;Cong Lai C;Yang LM;He YP;Zheng YT
通讯作者：
Zheng YT