生物活性

• 描述The nuclear enzyme poly(ADP-ribose) polymerase (PARP) plays an important role in the repair of DNA strand breaks, including those induced by radiation, thus making it a potential target for radiosensitizers. INO-1001 is a novel and potent inhibitor of PARP. INO-1001 at a concentration of 0.05 μM resulted in approximately 50% inhibition of PARP activity in CHO cells after 30 minutes treatment. And concentrations of 1 μM or greater resulted in more than 95% inhibition of the enzyme. Exponentially growing CHO cells were treated with 10 μM INO-1001 starting 30 min. prior to irradiation. INO-1001 significantly sensitized CHO cells to radiation. The initial slope of the survival curve for drug treated and irradiated cultures was greater than radiation alone. The enhancement ratio (ER) at 10% survival was 1.6. A similar radiosensitizing effect was observed in a murine tumor cell line with an ER of 1.7. The fibroblasts were also sensitized by the drug treatment with an ER of 1.4^[2]. Immediately after CCI (controlled cortical impact) or sham-injury mice received either INO-1001 (1.6 mg/kg) or vehicle via intracerebral injection (5 microl over 5 min) in a randomized fashion. Local treatment with INO-1001 preserved brain NAD+ levels 2 h after CCI. In the Morris water maze, treatment with INO-1001 reduced the latency to find the hidden platform and increased the time spent in the target quadrant versus vehicle after CCI^[3].
• 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
  NCT00272415	Melanoma	Phase 1	Terminated	-	-
  NCT00271765	Acute Myocardial Infarction	Phase 2	Completed	-	United States, Florida ... more >> Holy Cross Hospital Fort Lauderdale, Florida, United States, 33308 United States, Indiana Porter Hospital Valparaiso, Indiana, United States, 46383 United States, Minnesota St. Paul Heart Clinic St. Paul, Minnesota, United States, 55102 United States, New Jersey Newark, New Jersey, United States United States, Ohio Toledo Hospital Toledo, Ohio, United States, 43606 United States, Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania, United States United States, South Dakota Black Hills Cardiovascular Research Rapid City, South Dakota, United States, 57701 United States, Vermont Burlington, Vermont, United States United States, Virginia Sentara Norfolk General Hospital Norfolk, Virginia, United States United States, West Virginia West Virginia University Morgantown, West Virginia, United States, 26506 Israel Rambam Medical Center Haifa, Israel, 31096 Meir Medical Center Kfar Saba, Israel, 95847 Hasharon Medical Center Petach Tikva, Israel, 49100 Rabin Medical Center Petach Tikva, Israel, 49100 Rehovot, Israel Assaf Harofe Medical Centre Zerifin, Israel Collapse <<
  NCT00271167	Heart Diseases ... more >> Postoperative Complications Collapse <<	Phase 2	Terminated(It was determined t... more >>hat the study was not appropriate for demonstrating therapeutic benefit in the cardiopulmonary bypass patient population.) Collapse <<	-	United States, Massachusetts ... more >> Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215 United States, Oklahoma University of Oklahoma Oklahoma, Oklahoma, United States, 73152 United States, Pennsylvania University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104 United States, South Dakota Rapid City Regional Hospital Rapid City, South Dakota, United States United States, Texas Methodist Hospital Houston, Texas, United States, 77030 Australia, New South Wales Sydney, New South Wales, Australia Australia, South Australia Ashford Cardiac Clinic / Adelaide Cardiac Adelaide, South Australia, Australia Australia, Victoria St. Vincent's Hospital Melbourne, Victoria, Australia, 3065 Australia, Western Australia Royal Perth Hospital Perth, Western Australia, Australia, 6000 India Care Hospital Hyderabad, India Escorts Heart Institute and Research Centre New Delhi, India, 110029 Israel Wolfson Medical Centre Holon, Israel, 58100 Jerusalem, Israel Collapse <<

• 参考文献

• [1] Radovits T, Lin LN, et al. Poly(ADP-ribose) polymerase inhibition improves endothelial dysfunction induced by reactive oxidant hydrogen peroxide in vitro. Eur J Pharmacol. 2007 Jun 14;564(1-3):158-66.

  [2] Radiosensitization of human and rodent cell lines by INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase

  [3] Local administration of the poly(ADP-ribose) polymerase inhibitor INO-1001 prevents NAD+ depletion and improves water maze performance after traumatic brain injury in mice