A therapeutic approach to pantothenate kinase associated neurodegeneration was written by Sharma, Lalit Kumar;Subramanian, Chitra;Yun, Mi-Kyung;Frank, Matthew W.;White, Stephen W.;Rock, Charles O.;Lee, Richard E.;Jackowski, Suzanne. And the article was included in Nature Communications in 2018.Safety of 6-(Piperazin-1-yl)nicotinonitrile This article mentions the following:
Pantothenate kinase (PANK) is a metabolic enzyme that regulates cellular CoA (CoA) levels. There are three human PANK genes, and inactivating mutations in PANK2 lead to pantothenate kinase associated neurodegeneration (PKAN). Here we performed a library screen followed by chem. optimization to produce PZ-2891, an allosteric PANK activator that crosses the blood brain barrier. PZ-2891 occupies the pantothenate pocket and engages the dimer interface to form a PANK.ATP.Mg2+.PZ-2891 complex. The binding of PZ-2891 to one protomer locks the opposite protomer in a catalytically active conformation that is refractory to acetyl-CoA inhibition. Oral administration of PZ-2891 increases CoA levels in mouse liver and brain. A knockout mouse model of brain CoA deficiency exhibited weight loss, severe locomotor impairment and early death. Knockout mice on PZ-2891 therapy gain weight, and have improved locomotor activity and life span establishing pantazines as novel therapeutics for the treatment of PKAN. In the experiment, the researchers used many compounds, for example, 6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0Safety of 6-(Piperazin-1-yl)nicotinonitrile).
6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Safety of 6-(Piperazin-1-yl)nicotinonitrile
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics