CPI-1189. Centaur.
The efficacy of the proapoptotic cytokine tumor necrosis factor (TNF) alpha-inhibiting compound CPI-1189 has been demonstrated in various cell culture and animal models of chronic neurodegenerative and inflammatory diseases. CPI-1189 intracellularly inhibits the p38 mitogen-activated protein kinase phosphoactivation, thereby protecting against TNF alpha-induced neurodegeneration. Clinical proof-of-concept phase IIa trials in patients with Parkinson's disease and AIDS dementia complex were successful. These studies demonstrated clinical relevance for treatment with CPI-1189 (50 to 100 mg/day), which attenuated the deterioration in cognitive and/or motor function without any relevant side effects. Since the importance of neuroprotection is emerging, in particular in neurodegenerative diseases with concomitant observed immunological pro-apoptotic alterations in the central nervous system, long-term application of CPI-1189 could represent a promising future therapeutic alternative, in addition to neuroprotective compounds such as selegiline.
Müller
Thomas
T
Department of Neurology, St Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany. thomas.mueller@ruhr-uni-bochum.de
D000818:Animals; D002073:Butanes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004345:Drug Industry / Q000331:legislation & jurisprudence / Q000379:methods*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D009589:Nitrogen Oxides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D002073:Butanes; D009589:Nitrogen Oxides; C406025:CPI 1189