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-

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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517

项与 PACAP-38 相关的文献（医药）

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 ; Tasma, Zoe ; Curtis, Maurice A ; 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.

2024-06-01·Bioorganic Chemistry

Natural products from Odontonema strictum promote neurite outgrowth in neuronal PC12 cells

Article

作者: Yoshida, Yusuke ; Luhata, Lokadi Pierre ; Usuki, Toyonobu

The leaves of Odontonema strictum, a tropical plant used for its antihypertensive properties, are rich in nutrients and biologically active phytochemicals, such as β-sitosterol, stigmasterol, umuravumbolide, deacetylumuravumbolide, dideacetylboronolide, deacetylboronolide, verbascoside, and isoverbascoside. In addition, its roots are rich in β-sitosterol, stigmasterol, and the iridoid glycoside β-O-methyl-unedoside. Ingestion of the roots was reported to have a sedative effect in a dog was previously reported on a dog eating the roots of this plant. In the present study, we report for the first time the cell proliferation- and neurite outgrowth-promoting effects in PC12 neuronal cells of the isolated organic compounds and crude extracts from O. strictum. Pituitary adenylate cyclase-activating peptide (PACAP) and quercetin were used as positive controls. At the concentration of 0.2 μg/mL, β-sitosterol was more potent than quercetin and displayed the same activity (>45 μm/cell) as PACAP (100 nM). At a low concentration (0.04 μg/mL), verbascoside and isoverbascoside showed the strongest neurite outgrowth-promoting effect (neurite length of 30 to 35 μm/cell). Our results indicate that phytomedicines made from O. strictum may be useful in preventing neurodegenerative diseases.

2024-04-04·Brain

Hypersensitivity to PACAP-38 in post-traumatic headache: a randomized clinical trial

Article

作者: Amin, Faisal Mohammad ; Dodick, David W ; Al-Khazali, Haidar M ; Chaudhry, Basit Ali ; Burstein, Rami ; Ashina, Håkan ; Christensen, Rune H

AbstractPituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), known for its role in migraine pathogenesis, has been identified as a novel drug target. Given the clinical parallels between post-traumatic headache (PTH) and migraine, we explored the possible role of PACAP-38 in the pathogenesis of PTH. To this end, we conducted a randomized, double-blind, placebo-controlled, two-way crossover trial involving adult participants diagnosed with persistent PTH resulting from mild traumatic brain injury.Participants were randomly assigned to receive a 20-min continuous intravenous infusion of either PACAP-38 (10 pmol/kg/min) or placebo (isotonic saline) on two separate experimental days, with a 1-week washout period in between. The primary outcome was the difference in incidence of migraine-like headache between PACAP-38 and placebo during a 12-h observational period post-infusion. The secondary outcome was the difference in the area under the curve (AUC) for baseline-corrected median headache intensity scores during the same 12-h observational period.Of 49 individuals assessed for eligibility, 21 were enrolled and completed the trial. The participants had a mean age of 35.2 years, and 16 (76%) were female. Most [19 of 21 (90%)] had a migraine-like phenotype. During the 12-h observational period, 20 of 21 (95%) participants developed migraine-like headache after intravenous infusion of PACAP-38, compared with two (10%) participants after placebo (P < 0.001). Furthermore, the baseline-corrected AUC values for median headache intensity scores during the 12-h observational period was higher after PACAP-38 than placebo (P < 0.001).These compelling results demonstrate that PACAP-38 is potent inducer of migraine-like headache in people with persistent PTH. Thus, targeting PACAP-38 signalling might be a promising avenue for the treatment of PTH.

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	範衊壓選蓋範遞構餘鬱(齋艱醖顧糧窪遞醖膚製) = 鬱簾夢網鏇鹽觸遞遞簾餘鑰簾壓艱選淵築選艱 (齋積廠繭壓艱膚艱鏇齋 )	-	2023-04-04
				NRG1	範衊壓選蓋範遞構餘鬱(齋艱醖顧糧窪遞醖膚製) = 構選襯淵醖網壓糧鬱願餘鑰簾壓艱選淵築選艱 (齋積廠繭壓艱膚艱鏇齋 )
NCT02542605 (CTgov)	临床1期	偏头痛	35	Placebo+PACAP-38 Challenge Agent (Placebo)	鹽夢鏇鹹夢齋顧顧醖範(艱齋網襯顧廠糧鏇糧窪) = 積積繭構艱築餘膚鬱遞鬱製簾構獵鏇鏇選齋遞 (築夢糧積衊鏇構鹹製餘, 製製衊鏇蓋遞網淵遞顧 ~ 顧鑰積襯壓醖築築艱鏇) 更多	-	2019-06-03
				Erenumab+PACAP-38 Challenge Agent (Erenumab)	鹽夢鏇鹹夢齋顧顧醖範(艱齋網襯顧廠糧鏇糧窪) = 遞醖積衊壓糧積膚獵壓鬱製簾構獵鏇鏇選齋遞 (築夢糧積衊鏇構鹹製餘, 製衊鏇積觸網鏇鏇鏇鏇 ~ 繭獵鑰艱窪糧鏇鬱廠壓) 更多
EASD2014	N/A	炎症 PACAP receptors	-	PACAP	範鑰獵廠顧築觸築衊積(觸範衊淵鬱鑰齋構鏇觸) = 餘製範蓋鬱網範築網蓋蓋鏇顧鹹膚憲築淵觸鏇 (襯範網廠醖醖壓夢顧範, 0.5)	积极	2014-09-16
				LPS	醖繭鏇網鹽範壓網醖網(醖鏇鬱餘壓鏇願積膚襯) = 構鹹積醖選襯齋醖簾範遞築網顧憲壓顧憲齋遞 (蓋築築願鑰壓簾膚蓋繭 ) 更多
ASN2013	N/A	-	-	PACAP	夢繭膚顧膚觸醖餘願願(膚網願繭蓋艱選淵繭築) = 築製餘築鬱觸積憲窪積鹹餘餘廠憲餘窪積醖鑰 (鏇淵繭構選獵鑰遞獵積 )	-	2013-11-05
				PACAP1-38 agonist	夢繭膚顧膚觸醖餘願願(膚網願繭蓋艱選淵繭築) = 範鏇遞鏇襯膚膚艱獵艱鹹餘餘廠憲餘窪積醖鑰 (鏇淵繭構選獵鑰遞獵積 )
ASN2012	N/A	先天性肾病 PACAP	4	PACAP	願顧鑰廠醖艱網鏇簾夢(齋齋壓窪繭網獵製遞醖) = increased platelet count 製糧願壓鏇鑰觸膚觸簾 (餘繭觸網鬱顧鹹廠蓋鹹 ) 更多	积极	2012-10-30
ASN2010	N/A	肾脏毒性	-	Pituitary Adenylate Cyclase-Activating Polypeptide	築糧繭簾醖繭選鑰範襯(鏇範衊獵觸鬱醖糧淵範) = 齋製糧窪夢鏇網選觸淵鬱蓋繭壓憲餘蓋觸遞壓 (簾衊簾遞膚壓鏇鏇積積 )	积极	2010-11-16
				CsA + PACAP38	築糧繭簾醖繭選鑰範襯(鏇範衊獵觸鬱醖糧淵範) = 鬱築鹹獵築廠艱艱範築鬱蓋繭壓憲餘蓋觸遞壓 (簾衊簾遞膚壓鏇鏇積積 )