title: Stampidine as a promising antiretroviral drug candidate for pre-exposure prophylaxis against sexually transmitted HIV/AIDS.
abstract: BACKGROUND
  Pre-exposure prophylaxis (PrEP) is an evolving new approach to prevention of sexually transmitted HIV-1 that employs antiretroviral (ARV) agents prior to potential HIV-1 exposure in an attempt to reduce the likelihood of HIV-1 infection postexposure. The identification of new ARV agents with potent activity against multidrug-resistant HIV remains an unmet and urgent challenge in the field of PrEP.
  
  
  METHODS
  This article reviews the preclinical and early clinical activity and safety profile of stampidine, a novel antiretroviral (ARV) drug candidate that exhibits remarkable subnanomolar to low nanomolar in vitro antiretroviral potency against genotypically and phenotypically nucleoside reverse transcriptase inhibitor (NRTI)-resistant primary clinical HIV isolates, non-nucleoside RT-resistant HIV-1 isolates. Stampidine has a favorable pharmacokinetic profile in mice, rats, dogs and cats with 25 or 50 mg/kg tolerable dose levels yielding micromolar plasma concentrations that are 1000-fold higher than its in vitro IC(50) value against HIV. Stampidine has a favorable, safety profile in mice, rats, dogs and cats and it showed significant in vivo ARV activity in HIV-infected Hu-PBL-SCID mice as well as FIV-infected domestic cats. Furthermore, it did not cause any maternal toxicity, developmental toxicity or teratogenicity in rabbits treated at 10 - 40 mg/kg/day dose levels. In a recently completed first-in-human Phase I clinical trial, stampidine did not cause dose-limiting toxicity at single dose levels ranging from 5 to 25 mg/kg.
  
  
  CONCLUSIONS
  The favorable safety and activity profile of stampidine warrants its further development as a promising next-generation PrEP candidate to prevent the sexual transmission of HIV-1. The discovery of stampidine as a potent antiretroviral agent represents a significant step forward in the development of effective therapeutic as well as preventive strategies against HIV/AIDS.
authors.affiliation: Developmental Therapeutics Program, Children's Hospital Los Angeles, Children's Center for Cancer and Blood Diseases, Los Angeles, CA 90027, USA.
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Sanjive
authors.initials: S
authors.lastname: Qazi
authors.forename: Osmond
authors.initials: O
authors.lastname: D'Cruz
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017326:Clinical Trials, Phase III as Topic; D054306:Dideoxynucleotides / Q000494:pharmacology* / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D018119:Stavudine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D044966:Anti-Retroviral Agents; D054306:Dideoxynucleotides; C472384:stampidine; D013938:Thymidine Monophosphate; D018119:Stavudine