Development of PPL-138, a Novel Mixed NOP/Mu Partial Agonist for Treatment of CocaineUse Disorder
开发 PPL-138,一种用于治疗可卡因使用障碍的新型混合 NOP/Mu 部分激动剂
基本信息
- 批准号:10616932
- 负责人:
- 金额:$ 268.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-30 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:ADME StudyAffinityAgonistAlcoholsAnalgesicsAnimalsAttenuatedBehaviorBiologicalBiological AvailabilityBlood PressureBrainBuprenorphineBusinessesCardiovascular PhysiologyChemicalsChronicClinicalCocaineCocaine use disorderCodeConstipationCross-Over StudiesDataDevelopmentDiseaseDoseDrug InteractionsDrug KineticsDrug abuseDrug usageEffectivenessEyeFamilyFemaleFinancial SupportFormulationFreeze DryingFundingFutureGoalsHeart RateHumanHuman VolunteersHusbandIn VitroLaboratoriesLigandsMacaca mulattaMethamphetamineMethamphetamine use disorderNaltrexoneNamesNational Institute of Drug AbuseNicotineOpioidOpioid ReceptorPharmaceutical PreparationsPharmacologyPharmacotherapyPhase I Clinical TrialsPolymorphPowder dose formProcessPublic HealthRattusRelapseResearch PriorityRespirationRewardsRiversRodentRunningSafetySelf AdministrationSocietiesSodium ChlorideSpecific qualifier valueSystemTestingTherapeuticTimeToxic effectToxicogeneticsToxicologyTreatment EfficacyUniversitiesWorkaddictionalcohol abuse therapyantagonistcocaine self-administrationcocaine usecravingdesigndrug discoverydrug of abusedrug rewardeffective therapyefficacy studyexperienceexperimental studyfirst-in-humanforestin vivoinhibitormalemanufacturing process developmentmeetingsmethamphetamine abusemu receptorsnonhuman primatenovelopioid usepre-clinicalpreclinical developmentpreclinical studypreventprocess optimizationproduct developmentprogramspsychostimulantpublic-private partnershippulmonary functionreceptorsafety studyscreeningsexside effectstability testingstimulant abusesuccesstherapeutic development
项目摘要
Abstract
Currently, clinically used drug abuse medications exist for treatment of addiction to opiates, alcohol, and nicotine,
but not psychostimulants such as cocaine and methamphetamine (METH). PPL-138 is a non-selective opioid
receptor ligand with partial agonist activity at NOP and mu receptors, and antagonist activity at kappa and delta.
This compound, initially synthesized by Drs. Lawrence Toll and Stephen Husbands in a NIDA funded effort, has
now been licensed by Phoenix PharmaLabs (PPL), where Dr. Toll is a founder. This compound has been
demonstrated to be a potent inhibitor of both cocaine and METH self-administration and reinstatement in rats,
and to be not self-administered in rats or NHPs. Additional pharmacokinetic and safety studies in rodents and
NHPs have demonstrated little to no effect on respiration, constipation, heart rate or blood pressure, up to high
doses, thereby demonstrating a large apparent therapeutic window. It is our hypothesis that the increase in NOP
receptor affinity and activity, compared to buprenorphine, renders PPL-138 less rewarding and better at blocking
drug reward than buprenorphine, a compound demonstrated to reduce craving for psychostimulants. In this
proposed project, PPL will focus on cocaine use disorder (CUD) with an eye on continuing to METH use disorder
(MUD), in the future. To develop PPL-138, PPL has put together an experienced team with expertise in
pharmacology, chemical manufacturing, IND-enabling preclinical studies, regulatory, and first in human studies
and plan to take PPL-138 through each step, culminating in Phase I clinical trials. To accomplish these goals,
experiments have been designed to encompass the following 5 aims. Specific Aim 1 studies performed at Wake
Forest University will conduct final efficacy studies to determine whether PPL-138 is as effective in reducing
cocaine self-administration and relapse in NHPs as it is in rats. Specific Aim 2, will be continue chemical
manufacturing and encompass manufacturing process development and optimization, formulation, and GMP
drug product development and manufacturing. Specific Aim 3 directed by drug discovery and toxicology
consultants and performed primarily at Charles River Laboratories, will include a complete program of IND-
enabling in vitro and in vivo GLP toxicology studies, as well as supporting ADME studies. These will build upon
studies already completed by the previous licensee of this compound and current studies funded by PPL.
Specific Aim 4 will be directed by ICON and devoted to development of regulatory processes and filing an IND.
Finally, Specific Aim 5 will encompass first in human studies, directed by Dr. Frances Levin and run by ICON,
with Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies followed by a Single Dose
Crossover study in human volunteers. With the team of experts developing a very safe compound with a novel
mechanism of action, we expect to determine in humans whether a NOP/mu partial agonist can safely and
effectively reduce psychostimulant abuse. Importantly, PPL is committed to providing considerable financial
support for this project to make this in the spirit of a Public/Private Partnership, as specified in the proposal.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Frances Rudnick Levin其他文献
Frances Rudnick Levin的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Frances Rudnick Levin', 18)}}的其他基金
Augmenting cognitive-behavioral therapy with rTMS of the medial prefrontal and anterior cingulate cortices for the treatment of cocaine use disorder
利用内侧前额叶和前扣带皮层的 rTMS 增强认知行为疗法治疗可卡因使用障碍
- 批准号:
10681981 - 财政年份:2023
- 资助金额:
$ 268.02万 - 项目类别:
Development of PPL-138, a Novel Mixed NOP/Mu Partial Agonist for Treatment of CocaineUse Disorder
开发 PPL-138,一种用于治疗可卡因使用障碍的新型混合 NOP/Mu 部分激动剂
- 批准号:
10707176 - 财政年份:2022
- 资助金额:
$ 268.02万 - 项目类别:
Advancement of AEF0117 as a potential treatment for Cannabis Use Disorder: Preclinical toxicity and Clinical pharmacokinetic studies
AEF0117 作为大麻使用障碍潜在治疗方法的进展:临床前毒性和临床药代动力学研究
- 批准号:
10668477 - 财政年份:2021
- 资助金额:
$ 268.02万 - 项目类别:
The CB1 Signaling-Specific Inhibitor, AEF0117, for Cannabis Use Disorder: A Multi-Site Treatment Trial
CB1 信号传导特异性抑制剂 AEF0117,用于治疗大麻使用障碍:多部位治疗试验
- 批准号:
10249716 - 财政年份:2021
- 资助金额:
$ 268.02万 - 项目类别:
Randomized controlled trial of extended-release buprenorphine vs. sublingual buprenorphine for the treatment opioid use disorder patients using fentanyl analogues
使用芬太尼类似物缓释丁丙诺啡与舌下含服丁丙诺啡治疗阿片类药物使用障碍患者的随机对照试验
- 批准号:
9979016 - 财政年份:2020
- 资助金额:
$ 268.02万 - 项目类别:
Randomized controlled trial of extended-release buprenorphine vs. sublingual buprenorphine for the treatment opioid use disorder patients using fentanyl analogues
使用芬太尼类似物缓释丁丙诺啡与舌下含服丁丙诺啡治疗阿片类药物使用障碍患者的随机对照试验
- 批准号:
10158460 - 财政年份:2020
- 资助金额:
$ 268.02万 - 项目类别:
Shared Pharmacotherapeutic Strategies for Cannabinoid & Opioid Use Disorders
大麻素的共同药物治疗策略
- 批准号:
9098672 - 财政年份:2014
- 资助金额:
$ 268.02万 - 项目类别:
Shared Pharmacotherapeutic Strategies for Cannabinoid & Opioid Use Disorders
大麻素的共同药物治疗策略
- 批准号:
8742325 - 财政年份:2014
- 资助金额:
$ 268.02万 - 项目类别:
Shared Pharmacotherapeutic Strategies for Cannabinoid & Opioid Use Disorders
大麻素的共同药物治疗策略
- 批准号:
9306809 - 财政年份:2014
- 资助金额:
$ 268.02万 - 项目类别:
相似海外基金
Discovery of a High Affinity, Selective and β-arrestin Biased 5-HT7R Agonist
发现高亲和力、选择性和β-抑制蛋白偏向的 5-HT7R 激动剂
- 批准号:
10412227 - 财政年份:2022
- 资助金额:
$ 268.02万 - 项目类别:
Discovery of a High Affinity, Selective and β-arrestin Biased 5-HT7R Agonist
发现高亲和力、选择性和β-抑制蛋白偏向的 5-HT7R 激动剂
- 批准号:
10610473 - 财政年份:2022
- 资助金额:
$ 268.02万 - 项目类别:
Supplement to Discovery of a high affinity, selective and beta-arrestinbiased 5-HT7R Agonist Grant
对高亲和力、选择性和 β 抑制偏向 5-HT7R 激动剂发现的补充补助金
- 批准号:
10799162 - 财政年份:2022
- 资助金额:
$ 268.02万 - 项目类别:
NMDA RECEPTOR--AGONIST AFFINITY, EFFICACY/TRANSDUCTION
NMDA 受体——激动剂亲和力、功效/转导
- 批准号:
6639179 - 财政年份:2001
- 资助金额:
$ 268.02万 - 项目类别:
NMDA RECEPTOR--AGONIST AFFINITY, EFFICACY/TRANSDUCTION
NMDA 受体——激动剂亲和力、功效/转导
- 批准号:
6724797 - 财政年份:2001
- 资助金额:
$ 268.02万 - 项目类别:
General Anesthetics and nAcCHOR Agonist Affinity
全身麻醉药和 nAcCHOR 激动剂亲和力
- 批准号:
6636512 - 财政年份:2001
- 资助金额:
$ 268.02万 - 项目类别:
NMDA RECEPTOR--AGONIST AFFINITY, EFFICACY/TRANSDUCTION
NMDA 受体——激动剂亲和力、功效/转导
- 批准号:
6266928 - 财政年份:2001
- 资助金额:
$ 268.02万 - 项目类别:
NMDA RECEPTOR--AGONIST AFFINITY, EFFICACY/TRANSDUCTION
NMDA 受体——激动剂亲和力、功效/转导
- 批准号:
6539099 - 财政年份:2001
- 资助金额:
$ 268.02万 - 项目类别:
General Anesthetics and nAcCHOR Agonist Affinity
全身麻醉药和 nAcCHOR 激动剂亲和力
- 批准号:
6326889 - 财政年份:2001
- 资助金额:
$ 268.02万 - 项目类别:
General Anesthetics and nAcCHOR Agonist Affinity
全身麻醉药和 nAcCHOR 激动剂亲和力
- 批准号:
6520329 - 财政年份:2001
- 资助金额:
$ 268.02万 - 项目类别: