DP-b99

DP-b99 is a blood-brain barrier-permeable inhibitor of CYP2C9 and MMP-9, with a K_i value of 4.655 μM against CYP2C9. DP-b99 inhibits CYP2C9 via apparent non-competitive inhibition, mainly chelates pathological Zn²⁺ in the membrane environment, attenuates the elevation of intracellular Zn²⁺ and Ca²⁺ levels, delays seizure onset and reduces seizure severity, and also prevents MMP-9-dependent dendritic spine remodeling, β-dystroglycan cleavage and gelatinase activity. DP-b99 can be used in the research of acute ischemic stroke, epileptogenesis and stroke^[1][2][3]. In Vitro:DP-b99 (0.12-20 μM; 25 h) significantly reduces neuronal death in rat organotypic hippocampal slice cultures induced by Kainic acid (HY-N2309)^[2].
DP-b99 (0.12-20 μM; 1 h 10 min) inhibits KA-induced cleavage of β-dystroglycan, a marker of MMP-9 activity, in rat organotypic hippocampal slice cultures^[2].
DP-b99 (0.12-20 μM; 2 h) inhibits MMP-9-induced dendritic spine elongation and F-actin redistribution in primary cultured rat hippocampal neurons^[2].
DP-b99 (20 μM) is a cell-permeable chelator that reduces elevated intracellular Zn²⁺ in MIN6 mouse insulinoma cells to resting levels, even in the presence of physiological extracellular Ca^2+[3].
DP-b99 (0.01-20 μM; 20-30 min) dose-dependently attenuates L-type Ca²⁺ channel-mediated Zn²⁺ influx in MIN6 mouse insulinoma cells^[3].
DP-b99 (20 μM; 1 h) reduces the rate and amplitude of Zn²⁺ influx through L-type Ca²⁺ channels by 4-fold in primary rat embryonic cortical neurons^[3].
DP-b99 (20 μM; 1 h) reduces the elevation amplitude of intracellular Ca²⁺ in primary rat embryonic cortical neurons by 6-fold via L-type Ca²⁺ channels^[3].
DP-b99 (20 μM; 1 h) reduces depolarization-induced Zn²⁺ influx in the hippocampal pyramidal cell layer of acute mouse brain slices by approximately 6-fold^[3].
DP-b99 (20 μM) reduces the rate and amplitude of Zn²⁺ influx induced by the ionophore Pyrithione (HY-B1747) in primary rat embryonic cortical neurons by 2-fold, indicating that its activity is independent of ion entry pathways^[3].
DP-b99 (20 μM; 1 h) reduces Zn²⁺ -induced neuronal mortality from 30% to 17% in primary rat embryonic cortical neurons via L-type Ca²⁺ channels^[3].
DP-b99 (20 μM; 1 h) reduces the mortality rate of primary rat embryonic cortical neurons induced by Zn²⁺/Pyrithione from approximately 45%-52% to 30%, indicating that it exhibits protective activity independent of the Zn²⁺ entry pathway^[3]. In Vivo:DP-b99 (0.3 mg/kg; intraperitoneal injection; once daily for 9 consecutive days) significantly delays pentylenetetrazol (PTZ)-induced seizures in C57Bl/6 mice^[2].