IndraLab

Statements

REG3A inhibits KCNA3. 8 / 10
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"Using young male mice and rats we previously demonstrated that the Kv1.3 blocker PAP-1 when started 12 h after reperfusion dose-dependently reduces infarction and improves neurological deficit on day 8. However, these proof-of-concept findings are of limited translational value because the majority of strokes occur in patients over 65 and, when considering overall lifetime risk, in females."
34617690
sparser
"Although acting at different regions of the channel than Bax and MgTx (Cahalan & Chandy, xref ), PAP-1, Psora-4 and clofazimine also inhibit Kv1.3 and induce cytochrome c release and mitochondrial membrane depolarization."
22496117
sparser
"PAP-1 inhibits Kv1.3 with an IC 50 of 2 nM ( xref ), has a half-life of 3 hours in rodents, is orally available, brain penetrant and does not exhibit any long-term toxicity in rodents or primates ( xref ; xref ; xref )."
30043400
sparser
"A more recent study showed that PAP-1 inhibition of Kv1.3 channels in AD model APP/PS1 transgenic mice from 9 to 14 months of age resulted in decreased neuroinflammation and cerebral amyloid load, increased hippocampal neuronal plasticity, and improved behavioral deficits of treatment group mice with respect to the control group ( xref )."
33248207
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"Identification of Phase-I Metabolites of the Kv1.3 Blocker PAP-1 (5-(4-Phenoxybutoxy)psoralen) in the Rat NIH Public Access Author Manuscript.PAP-1 (5-(4-phenoxybutoxy)psoralen), a potent small-molecule blocker of the voltage-gated potassium Kv1.3 channel, is currently in pre-clinical development for psoriasis."
21070145
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"Interestingly, in a study using the middle cerebral artery occlusion model, a model of ischemic stroke that involves the formation of occlusive platelet thrombi in response to combined thrombotic and inflammatory stimuli[71], the selective Kv1.3 blocker Pap-1 dose-dependently reduced the infarct area in rodents, reducing microglial activation and improving neuronal survival[72]."
34348571
sparser
"We speculate that Kv1.3KO (or chronic Kv1.3 inhibition), but not acute inhibition of Kv1.3 by PAP-1, may cause a long-lasting change of synaptic release mechanism, which endows the Schaffer collateral-CA1 synapses with resistance to LPS-mediated acute effect on the STP."
30043400
reach
"Furthermore, pharmacological inhibition of Kv1.3 channel (PAP-1), but not Kir2.1, KCa3.1 or TWIK2, attenuated TLR3/4 receptor activation in macrophages."
35122955