Target Validation Information
Target ID T05387
Target Name Protein-glutamine gamma-glutamyltransferase
Target Type
Research
Drug Potency against Target Putrescine Drug Info Affinity = 50000 nM [537949]
Action against Disease Model Putrescine Kinetic evaluation of both of these subclasses revealed that they display reversible inhibition and are competitive with acyl donor TGase substrates at IC50 values as low as 18 |?M. An analysis of structure?activity relationships within these series of inhibitors permitted the identification of potentially important binding interactions. Further testing of some of the most potent inhibitors demonstrated their selectivity for TG2 and their potential for further development. [552833] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations By crossing Huntington's disease (HD) R6/1 transgenic mice with 'tissue' transglutaminase (TG2) knock-out mice, we have demonstrated that this multifunctional enzyme plays an important role in the neuronal death characterising this disorder in vivo. In fact, a large reduction in cell death is observed in R6/1, TG2(-/-) compared with R6/1 transgenic mice. In addition, we haveshown that the formation of neuronal intranuclear inclusions (NII) is potentiated in absence of the 'tissue' transglutaminase. These phenomena are paralleled by a significant improvement both in motor performances and survival of R6/1, TG2(-/-) versus R6/1 mice. Taken together these findings suggest an important role for tissue transglutaminase in the regulation of neuronal cell death occurring in Huntington's disease. [552833]
References
Ref 552833Cinnamoyl inhibitors of tissue transglutaminase. J Org Chem. 2008 Aug 1;73(15):5766-75. doi: 10.1021/jo8004843. Epub 2008 Jun 27.
Ref 537949Topical putrescine (Fibrostat) in treatment of hypertrophic scars: phase II study. Plast Reconstr Surg. 1996 Jan;97(1):117-23; discussion 124-5.

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