生物活性

• 靶点

  OAT1 IC50:0.81μM

  OAT3 IC50:0.41μM

• 描述HIV infection can be dramatically reduced by combination utilization of anti-retroviral therapy and anti-HIV IN drugs. Cabotegravir is such a strand transfer reaction inhibitor with an IC50 of 3nM in vitro. It showed potency against HIV-1 Ba-L, NL432, PBMCs and MT-4 with EC50 values of 0.22nM, 0.34nM, 0.57nM and 1.3nM, respectively, as well as exhibited antiproliferative effect against different cell lines, like IM-9, U-937, etc., with CC50 values ranging in 5.0-13μM, but 120 μM in unstimulated PBLs. Furthermore, Cabotegravir demonstrated a wonderful fold change when compared to other similar inhibitors, like Dolutegravir, in a screening of 49 site-directed mutants. The mean fold change detected in these mutants were quite different, as higher than 1700 or lower than 1.1 and with >=3 for 41 of these mutants, suggesting a wonderful resistance of this compound. In wild-type HIV-1 IIIB treated with Cabotegravir in dose escalation patterns of 0.256, 1.28, 6.4 and 32nM, no replication was observed at higher concentration throughout the experiment. Administration with Cabotegravir at 50mg/kg monthly in a macaques model showed a sexual difference in plasma concentration, lower in females than that in males. In a subsequent experiment, 8 female macaques showed a rectal tissue/plasma (T/P) ratio ranging from 0.14 to 1.43, similarly as that in unwashed rectal tissues from 0.15 to 1.13. Administration of Cabotegravir protected six of eight female rhesus macaques against SHIV challenges at weeks 0, 4, 5 and 7, providing further support for clinical studies of this compound.

• 动物研究
  剂量	Rhesus macaques: 10 mg/kg - 50 mg/kg[3] (i.m.)
  给药途径	i.m.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02076178	Infection, Human Immunodeficie... more >>ncy Virus Collapse <<	Phase 2	Completed	-	United States, California ... more >> GSK Investigational Site San Francisco, California, United States, 94158 United States, District of Columbia GSK Investigational Site Washington, District of Columbia, United States, 20005 United States, Georgia GSK Investigational Site Atlanta, Georgia, United States, 30339 United States, Massachusetts GSK Investigational Site Boston, Massachusetts, United States, 02215 United States, New Mexico GSK Investigational Site Santa Fe, New Mexico, United States, 87505 United States, New York GSK Investigational Site New York, New York, United States, 10016 GSK Investigational Site New York, New York, United States, 10032 GSK Investigational Site New York, New York, United States, 10065 United States, Pennsylvania GSK Investigational Site Philadelphia, Pennsylvania, United States, 19104 United States, Virginia GSK Investigational Site Newport News, Virginia, United States, 23606 Collapse <<
  NCT02076178	-	-	Completed	-	-
  NCT03639311	HIV Infections	Phase 2	Not yet recruiting	November 30, 2020	United States, Florida ... more >> GSK Investigational Site Not yet recruiting Fort Lauderdale, Florida, United States, 33316 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    United States, Texas GSK Investigational Site Not yet recruiting Dallas, Texas, United States, 75246 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com Collapse <<

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