"目录号: HY-14267
Anti-infection-
Lersivirine(UK-453061)是非核苷逆转录酶抑制剂（NNRTI），IC50为119 nM，对野生型和NNRTI抗性型毒株都有效。
HIVReverse Transcriptase
相关产品
Dolutegravir-Maraviroc-Elvitegravir-Atazanavir sulfate-Tenofovir Disoproxil Fumarate-Tipranavir-Triciribine-Emtricitabine-Efavirenz-Miltefosine-Ritonavir-Delavirdine mesylate-Lamivudine-Abacavir-BI 224436-
生物活性
Description
Lersivirine(UK-453061) is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI, IC50=119 nM) with a unique resistance profile that exhibits potent antiretroviral activity against wild-type human immunodeficiency virus and clinically relevant NNRTI-resistant strains.IC50 value: 0.119 uM [1]Target: NNRTIUK-453061(Compound 5) demonstrated excellent activity against large panels of wild type and drug-resistant HIV consistent with the encouraging profile demonstrated against the isolated RT enzymes. Compound 5 can be readily prepared in multi-gram quantities by virtue of the efficient and concise synthetic route. The compound also has good aqueous solubility and formulation characteristics which enable further in vivo evaluation. Clinical trials evaluating the potential of 5 (UK-453,061, lersivirine) to treat HIV infection are proceeding and further progress will be reported in due course [1].At clinically relevant lersivirine doses (500-1,000 mg total daily dose), the mean plasma exposure of midazolam was reduced in a dose-dependent manner by 20-36 %. Co-administration of lersivirine 1,000 mg QD with OCs had minor PK effects, increasing ethinylestradiol exposure by 10 % and reducing levonorgestrel exposure by 13 % [2]. Mated Crl:CD1(ICR) mice were administered 0, 150, 350, and 500 mg/kg lersivirine once daily by oral gavage on gestation days 6 to 17, followed by cesarean section on gestation day 18. The first 2 days of dosing for the high-dose group were done at 250 mg/kg to allow induction of hepatic metabolizing enzymes, after which the dose was increased to 500 mg/kg/day [3].
Clinical Trial
NCT01050751
Pfizer
Healthy Volunteers
February 2010
Phase 1
NCT01220232
Pfizer-ViiV Healthcare
Healthy Volunteers
November 2010
Phase 1
NCT00936871
Pfizer
Healthy Volunteers
January 2010
Phase 1
NCT01603485
Pfizer-ViiV Healthcare
Healthy Volunteer
June 2012
Phase 1
NCT01230385
Pfizer-ViiV Healthcare
Healthy Volunteers
October 2010
Phase 1
NCT01099748
Pfizer
Healthy Volunteers
May 2010
Phase 1
NCT00925535
Pfizer
Healthy Volunteers
May 2010
Phase 1
NCT01254656
Pfizer-ViiV Healthcare
HIV-1
February 2011
Phase 2
View MoreCollapse
References
[1].Mowbray CE, et al. Pyrazole NNRTIs 4: selection of UK-453,061 (lersivirine) as a development candidate. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5857-60.
[2].Davis J, et al. The effect of lersivirine, a next-generation NNRTI, on the pharmacokinetics of midazolam and oral contraceptives in healthy subjects. Eur J Clin Pharmacol. 2012 Nov;68(11):1567-72.
[3].Cappon GD, et al. Developmental toxicity study of lersivirine in mice. Birth Defects Res B Dev Reprod Toxicol. 2012 Jun;95(3):225-30.