Inhibition of human prolyl hydroxylase as common biochemical denominator of the non-sedative effects of thalidomide in man.
The two main non-sedative effects of thalidomide (2-phtalimido-glutarimide) in man are the embryopathy, which finally forced termination of its use as a sedative, and the excellent efficacy in leprosy reactions, alone for whose prevention and treatment the drug is still available. Both effects can be explained on the molecular level by assuming that a non-sedative metabolite of thalidomide mediates inhibition of human prolyl hydroxylase, as suggested by steric considerations and correlation to known data. This metabolite may well be a suitable model compound for drugs designed for selective fibrosuppression and selective immunosuppression.
D003094:Collagen / Q000378:metabolism; D006801:Humans; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D011392:Proline; D013792:Thalidomide / Q000378:metabolism / Q000494:pharmacology*
D013792:Thalidomide; D003094:Collagen; D011392:Proline; D011393:Procollagen-Proline Dioxygenase