TY - JOUR
T1 - Selective gelatinase inhibitor neuroprotective agents cross the blood-brain barrier
AU - Gooyit, Major
AU - Suckow, Mark A.
AU - Schroeder, Valerie A.
AU - Wolter, William R.
AU - Mobashery, Shahriar
AU - Chang, Mayland
PY - 2012/10/17
Y1 - 2012/10/17
N2 - SB-3CT, a potent and selective inhibitor of matrix metalloproteinase-2 and -9, has shown efficacy in several animal models of neurological diseases. One of the greatest challenges in the development of therapeutics for neurological diseases is the inability of drugs to cross the blood-brain barrier. A sensitive bioanalytical method based on ultraperformance liquid chromatography with multiple-reaction monitoring detection was developed to measure levels of SB-3CT, its active metabolite, the α-methyl analogue, and its p-hydroxy metabolite in plasma and brain. The compounds are rapidly absorbed and are readily distributed to the brain. The pharmacokinetic properties of these gelatinase inhibitors and the efficacy shown by SB-3CT in animal models of stroke, subarachnoid hemorrhage, and spinal cord injury indicate that this class of compounds holds considerable promise in the treatment of diseases of the central nervous system.
AB - SB-3CT, a potent and selective inhibitor of matrix metalloproteinase-2 and -9, has shown efficacy in several animal models of neurological diseases. One of the greatest challenges in the development of therapeutics for neurological diseases is the inability of drugs to cross the blood-brain barrier. A sensitive bioanalytical method based on ultraperformance liquid chromatography with multiple-reaction monitoring detection was developed to measure levels of SB-3CT, its active metabolite, the α-methyl analogue, and its p-hydroxy metabolite in plasma and brain. The compounds are rapidly absorbed and are readily distributed to the brain. The pharmacokinetic properties of these gelatinase inhibitors and the efficacy shown by SB-3CT in animal models of stroke, subarachnoid hemorrhage, and spinal cord injury indicate that this class of compounds holds considerable promise in the treatment of diseases of the central nervous system.
KW - Gelatinase inhibitors
KW - SB-3CT
KW - brain delivery
KW - matrix metalloproteinases
UR - http://www.scopus.com/inward/record.url?scp=84867627450&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867627450&partnerID=8YFLogxK
U2 - 10.1021/cn300062w
DO - 10.1021/cn300062w
M3 - Article
C2 - 23077716
AN - SCOPUS:84867627450
VL - 3
SP - 730
EP - 736
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 10
ER -