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Discovery of selective KOR ligands for the treatment of resistant depression and neuropathic pain

Implementing Organization

CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow
Principal Investigator
Dr Prem Prakash Yadav
Scientist
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CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow

About

Objective: Design, synthesis and optimization of KOR antagonist and biased agonis . Design, synthesis and optimization of Nav 1.7 and TRPV 1 antagonist .GPCR profiling (KOR) and selectivity screening (KOR vs MOR & DOR) and biased score for agonist . Activity profiling against of Nav 1.7 and TRPV 1 . Optimization of leads based on DMPK properties, physicochemical parameters and parameters for CNS drug likeness (BBB penetration, logP, LLE etc). Establishment of efficacy in secondary in vivo models of TRD and neuropathic pain as per the decision tree. Identification of Leads for follow-up project regarding preclinical safety and toxicity studies. . Design, synthesis and optimization of KOR antagonist and biased agonist . GPCR profiling (KOR) and selectivity screening (KOR vs MOR & DOR) and biased score for agonist . Optimization of leads based on DMPK properties, physicochemical parameters and parameters for CNS drug likeness (BBB penetration, logP, LLE etc. Establishment of efficacy in secondary in vivo models of TRD and neuropathic pain as per the decision tree. Identification of Leads for follow-up project regarding preclinical safety and toxicity studies. 1) Design and synthesis of novel BBB penetrating peptides and peptidomimetic modulators of TRPV1 and Nav 1.7 .Using BBB permeable vectors as a carrier of newly designed and known compounds .Biodegradable nanoparticle conjugates to deliver these modulators into the brain . In vitro screening of NCEs for novel antagonists of Nav1 .7 and TRPV1 . Determine the in vivo efficacy of novel Nav1. 7 or TRPV1 antagonist in rat model of neuropathic pain.

Funding Organization
Funding Organization
Council of Scientific and Industrial Research
Quick Information
Area of Research
Life Sciences & Biotechnology
Focus Area
Neuropathic pain
Start Year
2020
End Year
2025
Status
Completed
Output
No. of Research Paper
00
Technologies (If Any)
00
No. of PhD Produced
N/A
Startup (If Any)
00
No. of Patents
Filed :00
Grant :00
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