PACAP-38(PACAP-38) - 药物靶点：AC_专利_临床

概要

基本信息

药物类型

重组多肽

别名

PACAP、Pituitary adenylate cyclase activating polypeptide

+ [3]

靶点

AC

作用机制

AC刺激剂(腺苷酸环化酶家族刺激剂)

治疗领域

免疫系统疾病神经系统疾病心血管疾病+ [3]

在研适应症-

非在研适应症

哮喘药物性心脏毒性非小细胞肺癌+ [1]

原研机构

Tulane University Hospital & Clinic

在研机构-

非在研机构

National Institutes of Health

Endo International Plc

Tulane University Hospital & Clinic

最高研发阶段终止临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

3

项与 PACAP-38 相关的临床试验

NCT05635604 / CompletedN/AIIT

Molecular Stratification of Signaling Pathways Underlying Migraine Pathophysiology.

To investigate whether administration of calcitonin gene-related peptide (CGRP) binding monoclonal antibodies eptinezumab prevents pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) induced migraine attacks in migraine without aura patients.

开始日期2023-03-01

申办/合作机构

Danish Headache Center

ChiCTR2100043157 / Recruiting早期临床1期IIT

To explore the role of vasoactive peptide CGRP and PACAP-38 in the occurrence and diagnosis of migraine in children

开始日期2021-11-01

申办/合作机构

山东大学齐鲁医院

NCT02542605 / Completed临床1期

Phase I, Randomized, Parallel-group, Double-Blind, Placebo-Controlled, Single Dose Study to Evaluate the Blockade of CGRP Receptor by AMG 334 in Preventing PACAP-38 Induced Migraine-like Attacks in Migraine Patients

Phase I, Randomized, Parallel-group, Double-Blind, Placebo-Controlled, Single Dose Study to Evaluate the Blockade of CGRP Receptor by AMG 334 in Preventing PACAP-38 Induced Migraine-like Attacks in Migraine Patients.

开始日期2015-11-11

申办/合作机构

Amgen, Inc.

100 项与 PACAP-38 相关的临床结果

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100 项与 PACAP-38 相关的转化医学

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100 项与 PACAP-38 相关的专利（医药）

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518

项与 PACAP-38 相关的文献（医药）

2024-11-01·Journal of Comparative Physiology A

Same same, but different: exploring the enigmatic role of the pituitary adenylate cyclase-activating polypeptide (PACAP) in invertebrate physiology

Article

作者: Kiss, Tibor ; Gálik, Bence ; Kiss, Bence ; Pirger, Zsolt ; Urbán, Péter ; Kemenes, György ; Tapodi, Antal ; Reglődi, Dóra ; Schmidt, János ; Koene, Joris M ; Fodor, István ; Tóth, Gábor K

AbstractEvidence has been accumulating that elements of the vertebrate pituitary adenylate cyclase-activating polypeptide (PACAP) system are missing in non-chordate genomes, which is at odds with the partial sequence-, immunohistochemical-, and physiological data in the literature. Multilevel experiments were performed on the great pond snail (Lymnaea stagnalis) to explore the role of PACAP in invertebrates. Screening of neuronal transcriptome and genome data did not reveal homologs to the elements of vertebrate PACAP system. Despite this, immunohistochemical investigations with an anti-human PAC1 receptor antibody yielded a positive signal in the neuronal elements in the heart. Although Western blotting of proteins extracted from the nervous system found a relevant band for PACAP-38, immunoprecipitation and mass spectrometric analyses revealed no corresponding peptide fragments. Similarly to the effects reported in vertebrates, PACAP-38 significantly increased cAMP synthesis in the heart and had a positive ionotropic effect on heart preparations. Moreover, it significantly modulated the effects of serotonin and acetylcholine. Homologs to members of Cluster B receptors, which have shared common evolutionary origin with the vertebrate PACAP receptors, PTHRs, and GCGRs, were identified and shown not to be expressed in the heart, which does not support a potential role in the mediation of PACAP-induced effects. Our findings support the notion that the PACAP system emerged after the protostome-deuterostome divergence. Using antibodies against vertebrate proteins is again highlighted to have little/no value in invertebrate studies. The physiological effects of vertebrate PACAP peptides in protostomes, no matter how similar they are to those in vertebrates, should be considered non-specific.

2024-10-01·Biomedicine & Pharmacotherapy

Injectable Gel-PEG hydrogels as promising delivery system for intravitreal PACAP release: Novel therapeutics for unilateral common carotid artery occlusion induced retinal ischemia

Article

作者: Yang, Yuan ; Shu, Qin ; Nie, WanQin ; Ju, YaHan ; Liang, XiaoYi ; Guo, YongLin ; Yang, XueFeng ; Gu, Ping ; Chen, XiRui ; Li, Lin ; Li, XiaoJing ; Chen, MoXin

Retinal ischemia is an ophthalmic emergency often caused by cardiovascular diseases, leading to irreversible vision loss and even blindness. Innovative retinal ischemia treatments are needed due to limited options. The pathological mechanisms involve retinal cell apoptosis and microglial activation. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a well distributed neuropeptide found in both central nervous system and peripheral organs. Though it shows great anti-apoptosis and anti-microglia activation properties, it is rapidly cleared by intravitreal injection. Herein, we established a novel poly(ethylene glycol) (PEG) hydrogel system by cross-linking 4arm-PEG-NHS and 4arm-PEG-NH₂ to load PACAP (PACAP@Gel-PEG), which exhibited great fluidity, injectability, structural recovery ability, moderate swelling ratio and drug release ability that were appropriate for drug delivery. Then the safety and effectiveness of the PACAP@Gel-PEG were evaluated in vitro in three retinal cell lines (ARPE-19, 661 W and rRMC) and in vivo using the unilateral common carotid artery occlusion (UCCAO) mice model. The CCK-8 test and live/dead staining demonstrated that PACAP@Gel-PEG exhibited excellent biocompatibility in three retinal cell lines. Furthermore, after PACAP@Gel-PEG treatment, a great anti-apoptotic effect was observed in cells treated by CoCl₂. Application of PACAP@Gel-PEG greatly improved the therapeutic efficacy of PACAP in restoring retinal function, maintaining retinal integrity, and suppressing apoptosis and microglia activation in retinal tissues. Moreover, in mice, the biosafety of PACAP@Gel-PEG was confirmed by H&E staining of systemic organs. Taken together, our results demonstrated PACAP@Gel-PEG as a promising therapeutic option for retinal ischemia, providing new strategies for vision restoration.

2024-08-01·British Journal of Pharmacology

Pharmacology of PACAP and VIP receptors in the spinal cord highlights the importance of the PAC₁ receptor

Article

作者: Rees, Tayla A ; O'Carroll, Simon J ; Walker, Christopher S ; Guo, Song ; Faull, Richard L M ; Tan, Sheryl ; Hay, Debbie L ; Curtis, Maurice A ; Tasma, Zoe ; Christensen, Sarah L

Background and PurposeThe spinal cord is a key structure involved in the transmission and modulation of pain. Pituitary adenylate cyclase‐activating peptide (PACAP) and vasoactive intestinal peptide (VIP), are expressed in the spinal cord. These peptides activate G protein‐coupled receptors (PAC1, VPAC1 and VPAC2) that could provide targets for the development of novel pain treatments. However, it is not clear which of these receptors are expressed within the spinal cord and how these receptors signal.Experimental ApproachDissociated rat spinal cord cultures were used to examine agonist and antagonist receptor pharmacology. Signalling profiles were determined for five signalling pathways. The expression of different PACAP and VIP receptors was then investigated in mouse, rat and human spinal cords using immunoblotting and immunofluorescence.Key ResultsPACAP, but not VIP, potently stimulated cAMP, IP1 accumulation and ERK and cAMP response element‐binding protein (CREB) but not Akt phosphorylation in spinal cord cultures. Signalling was antagonised by M65 and PACAP6–38. PACAP‐27 was more effectively antagonised than either PACAP‐38 or VIP. The patterns of PAC1 and VPAC2 receptor‐like immunoreactivity appeared to be distinct in the spinal cord.Conclusions and ImplicationsThe pharmacological profile in the spinal cord suggested that a PAC1 receptor is the major functional receptor subtype present and thus likely mediates the nociceptive effects of the PACAP family of peptides in the spinal cord. However, the potential expression of both PAC1 and VPAC2 receptors in the spinal cord highlights that these receptors may play differential roles and are both possible therapeutic targets.

100 项与 PACAP-38 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
药物性心脏毒性	临床1期	美国	Tulane University Hospital & Clinic	2017-07-15
脑卒中	临床1期	美国	National Institutes of Health	2006-11-15
哮喘	临床1期	-	Endo International Plc	-
哮喘	临床1期	-	Tulane University Hospital & Clinic	-
非小细胞肺癌	临床1期	-	Tulane University Hospital & Clinic	-
非小细胞肺癌	临床1期	-	Endo International Plc	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2023	N/A	非小细胞肺癌	-	PACAP-27	衊鏇糧顧壓壓廠鬱窪襯(願壓選壓醖選遞鑰壓鏇) = 簾繭衊壓繭願鏇窪膚鬱遞淵築鹽淵範襯構醖簾 (窪糧鹹艱襯範淵構糧積 )	-	2023-04-04
				NRG1	衊鏇糧顧壓壓廠鬱窪襯(願壓選壓醖選遞鑰壓鏇) = 淵鹹顧窪窪網積夢壓顧遞淵築鹽淵範襯構醖簾 (窪糧鹹艱襯範淵構糧積 )
NCT02542605 (CTgov)	临床1期	偏头痛	35	Placebo+PACAP-38 Challenge Agent (Placebo)	觸衊窪範網願製齋鹽艱(艱壓積選網膚憲鬱衊蓋) = 淵觸窪窪網範築繭顧壓獵膚鑰艱積築醖願觸觸 (艱鑰顧鹹夢憲顧壓簾鬱, 淵醖淵鹹醖鹽鬱選憲夢 ~ 網餘築範鹹網餘鬱襯蓋) 更多	-	2019-06-03
				Erenumab+PACAP-38 Challenge Agent (Erenumab)	觸衊窪範網願製齋鹽艱(艱壓積選網膚憲鬱衊蓋) = 選餘襯鏇觸廠艱範糧獵獵膚鑰艱積築醖願觸觸 (艱鑰顧鹹夢憲顧壓簾鬱, 窪蓋築廠願鑰築醖艱衊 ~ 範鬱觸艱顧鹽襯窪廠鬱) 更多
EASD2014	N/A	炎症 PACAP receptors	-	PACAP	網觸襯選蓋觸網選襯衊(觸鏇鏇窪簾窪獵積膚簾) = 願糧觸齋製廠廠膚觸簾遞獵遞膚獵製艱糧糧鑰 (製鬱醖夢構窪鹹艱鑰窪, 0.5)	积极	2014-09-16
				LPS	窪襯壓餘蓋膚鹽構鏇廠(夢繭網願襯鏇醖壓夢廠) = 糧繭鹽選膚網構鬱構獵選襯構餘蓋膚鏇網憲獵 (鹹糧獵鏇選鏇蓋淵觸蓋 ) 更多
ASN2013	N/A	-	-	PACAP	顧夢繭顧鏇壓顧製廠壓(淵積範膚網繭構餘築壓) = 鏇觸願範願憲鏇廠窪鏇顧夢蓋鑰選遞觸鬱蓋遞 (憲艱夢網廠範醖壓積鑰 )	-	2013-11-05
				PACAP1-38 agonist	顧夢繭顧鏇壓顧製廠壓(淵積範膚網繭構餘築壓) = 網鏇窪醖蓋糧顧積齋觸顧夢蓋鑰選遞觸鬱蓋遞 (憲艱夢網廠範醖壓積鑰 )
ASN2012	N/A	先天性肾病 PACAP	4	PACAP	廠選憲鬱遞壓糧艱觸範(餘簾鑰醖夢襯繭簾願遞) = increased platelet count 夢築鹹鏇衊鹽觸憲簾顧 (壓憲糧築壓選餘憲壓夢 ) 更多	积极	2012-10-30
ASN2010	N/A	肾脏毒性	-	Pituitary Adenylate Cyclase-Activating Polypeptide	鬱積鏇鑰艱窪壓獵獵齋(鹹淵繭獵窪範憲遞遞遞) = 範憲顧膚築構廠鑰壓構積齋觸膚齋網齋構膚餘 (壓範鹽觸膚齋窪觸鬱簾 )	积极	2010-11-16
				CsA + PACAP38	鬱積鏇鑰艱窪壓獵獵齋(鹹淵繭獵窪範憲遞遞遞) = 鹽築願製觸窪選網餘膚積齋觸膚齋網齋構膚餘 (壓範鹽觸膚齋窪觸鬱簾 )