中文版 | English
Arid
项目编号1R41DA050364-01
Optimization of Betulinic Acid analogs for T-type calcium channel inhibition for non-addictive relief of chronic pain
KHANNA, RAJESH
主持机构NATIONAL INSTITUTE ON DRUG ABUSE
开始日期2019
结束日期2020
资助经费224696(USD)
项目类别SBIR-STTR RPGs
资助机构US-NIH（美国国立卫生研究院）
语种英语
国家美国
英文简介NARRATIVE Medicinal plants represent a significant reservoir of unexplored substances for early-stage drug discovery. Here, Regulonix LLC proposes to develop novel small molecules to target low-voltage activated T-type calcium (Cav3.2) channel, a key protein in pathogenesis of neuropathic pain including chemotherapy-induced peripheral neuropathy (CIPN). We will design orally available T-type channel antagonists, analogs of the extract betulinic acid (BA) which we recently discovered from a desert lavender plant. First, channel specificity and biophysical properties of the best Cav3.2 antagonists will be elucidated to gain mechanistic and safety information and to document the unique pathway for function in relevant neuronal cells including human neurons. Next, BA analogs will be tested in a neurotoxicity model (rotarod) and cellular pharmacological assays that provide information about efficacy and function. Whether BA analogs are opioid sparing will also be tested. Finally, drug properties of an optimized Cav3.2 antagonist and its in vivo effectiveness will be determined in the paclitaxel model of CIPN.
英文关键词Absence of pain sensation addiction Affect Afferent Neurons American Amitriptyline Analgesics analog Antidepressive Agents Arizona Axon Baclofen base Betulinic Acid Biological Assay biophysical properties Calcium Calcium Channel Blockers Calcium Channel Inhibition cancer pain Cancer Patient cancer survival cancer therapy Cell-Mediated Cytolysis Cells central sensitization chemotherapeutic agent chemotherapy Chemotherapy-induced peripheral neuropathy Chemotherapy-Oncologic Procedure Chronic chronic pain chronic pain relief chronic painful condition Clinical Clinical Trials Complex compliance behavior Complication counterscreen Coupled design dorsal horn Dose-Limiting drug discovery Drug Kinetics Drug Targeting duloxetine Dysesthesias effective therapy Effectiveness Esthesia Feeling Fiber G-Protein-Coupled Receptors Human improved In Vitro in vivo Indigenous inhibitor/antagonist Ion Channel Laboratories Lavandula Lead Malignant Neoplasms Mediating Mediator of activation protein Medical Medicinal Plants meetings Modeling Muscle relaxants Natural Products Neuraxis neuronal excitability Neurons Neuropathy neurotoxic neurotoxicity neurotransmission non-opioid analgesic Norepinephrine novel novel therapeutics Numbness Opiate Addiction Opioid opioid misuse Opioid Receptor opioid sparing opioid use Oral Paclitaxel Pain Pain management pain model pain relief pain signal painful neuropathy Paresthesia Pathogenesis Pathway interactions Peripheral Peripheral Nerves Peripheral Nervous System Peripheral Nervous System Diseases Pharmaceutical Preparations Pharmacology Pharmacotherapy Phase Plants Platinum Compounds preclinical study Prevalence Property Protein Isoforms Proteins Quality of life Rattus Regimen Regulation reuptake Role Safety screening Sensory sensory stimulus Serotonin Shock side effect Site small molecule somatosensory Southwestern United States Specificity Spinal Spinal Cord Spinal Ganglia Structure success Survival Rate synaptic function T-Type Calcium Channels taxane Testing Tissues Translating Treatment Protocols Universities venlafaxine Vinca Alkaloids voltage Work
URL9907601
资源类型项目
条目标识符http://119.78.100.177/qdio/handle/2XILL650/356171
推荐引用方式
GB/T 7714		 KHANNA, RAJESH.Optimization of Betulinic Acid analogs for T-type calcium channel inhibition for non-addictive relief of chronic pain.2019.
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