| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T47623 | ||||
| Target Name | Heparanase | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | PI-88 | Drug Info | Ki = 7.9 nM | [552981] | |
| Action against Disease Model | PI-88 | PI-88 inhibit heparanase at Ki 8 nM. The IC50 values of PI-88 in growth factor-induced HUVEC proliferation assays are 20-30 uM. PI-88 at 10 |?M inhibits HUVEC tube formation by 29% | [536451] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Twenty five third-trimester placenta samples (weeks 36-41) were studied applying real time RTPCR and immunostaining. Ten cases were placentas of elective cesarean sections, 8 cases were of normal vaginal deliveries and 7 samples were placentas of intra-uterine growth restriction (IUGR) fetuses. Skin and lung tissues of heparanase over-expressing mice and heparanase knock-outmice were subjected to immunostaining.Sections obtained from vaginal and IUGR placentas revealed 2 folds increased levels of heparanase, TFPI-2 and VEGF-A compared to placentas from elective cesareansections in maternal decidua as well as in fetal placenta elements. Interestingly, abundance of TFPI staining in the intra-villous blood was observed in placentas of vaginal and IUGR deliveries. Heparanase effect on TFPI release to the blood was supported by immunostaining of heparanase over-expressing and heparanase knock-out mice tissues.In regard to our previous data on early pregnancy losses,the present data strengthen the understanding that in placental vascular complications levels of heparanase, TFPI-2 and VEGF-A increase. In the process of delivery, heparanase may have a regulatory role on TFPI release to fetal circulation | [552981] | |||
| References | |||||
| Ref 552981 | Development of a colorimetric assay for heparanase activity suitable for kinetic analysis and inhibitor screening. Anal Biochem. 2010 Jan 1;396(1):112-6. doi: 10.1016/j.ab.2009.09.007. Epub 2009 Sep 11. | ||||
| Ref 536451 | PI-88 and novel heparan sulfate mimetics inhibit angiogenesis. Semin Thromb Hemost. 2007 Jul;33(5):557-68. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.