Parentide(Parentide) - 药物靶点：TRPV1_在研适应症：神经痛_专利_临床

概要

基本信息

药物类型

合成多肽

别名

靶点

TRPV1

作用机制

TRPV1拮抗剂(类香草素受体拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C48H88N14O12S

InChIKeyMKMGHNXKCFXFRM-NGTAMTFRSA-N

CAS号1202877-06-2

序列信息

Sequence Code 66380

关联

2

项与 Parentide 相关的临床试验

EUCTR2022-001374-60-ES / Not yet recruiting临床2/3期

A randomized, double blinded, placebo controlled clinical trial to evaluate the antipruritic efficacy of the topical application of PARENTIDE cream in histamine-induced itch in healthy volunteers - PARENTIDE cream for the treatment of pruritus

开始日期2022-07-21

申办/合作机构

BCN Peptides SA

EUCTR2016-002846-21-ES / Not yet recruiting临床2期

CLINICAL TRIAL PHASE IIa PROOF OF CONCEPT, DOUBLE BLIND, RANDOMIZED, PLACEBO-CONTROLLED IN PATIENTS WITH NEUROPATHIC PAIN DUE TO PERIPHERAL NERVE INJURY - PARENTIDE POC IN NEUROPATHY

开始日期2017-04-10

申办/合作机构-

100 项与 Parentide 相关的临床结果

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100 项与 Parentide 相关的转化医学

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100 项与 Parentide 相关的专利（医药）

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3

项与 Parentide 相关的文献（医药）

2021-10-01·Bioorganic Chemistry2区 · 化学

DD04107-Derived neuronal exocytosis inhibitor peptides: Evidences for synaptotagmin-1 as a putative target

2区 · 化学

Article

作者: Bonache, M Ángeles ; Martín-Martínez, Mercedes ; Velázquez-Campoy, Adrián ; Zamora-Carreras, Héctor ; Devesa, Isabel ; Fernández-Carvajal, Asia ; Baamonde, Ana ; Treviño, Miguel A ; González-Rodríguez, Sara ; Ferrer-Montiel, Antonio ; Lagartera, Laura ; Abian, Olga ; González-Muñiz, Rosario ; Jiménez, M Ángeles ; Butrón, Daniel

The analgesic peptide DD04107 (Pal-EEMQRR-NH₂) and its acetylated analogue inhibit α-calcitonin gene-related peptide (α-CGRP) exocytotic release from primary sensory neurons. Examining the crystal structure of the SNARE-Synaptotagmin-1(Syt1) complex, we hypothesized that these peptides could inhibit neuronal exocytosis by binding to Syt1, hampering at least partially its interaction with the SNARE complex. To address this hypothesis, we first interrogate the role of individual side-chains on the inhibition of α-CGRP release, finding that E1, M3, Q4 and R6 residues were crucial for activity. CD and NMR conformational analysis showed that linear peptides have tendency to adopt α-helical conformations, but the results with cyclic analogues indicated that this secondary structure is not needed for activity. Isothermal titration calorimetry (ITC) measurements demonstrate a direct interaction of some of these peptides with Syt1-C2B domain, but not with Syt7-C2B region, indicating selectivity. As expected for a compound able to inhibit α-CGRP release, cyclic peptide derivative Pal-E-cyclo[EMQK]R-NH₂ showed potent in vivo analgesic activity, in a model of inflammatory pain. Molecular dynamics simulations provided a model consistent with K_D values for the interaction of peptides with Syt1-C2B domain, and with their biological activity. Altogether, these results identify Syt1 as a potential new analgesic target.

2016-01-01·Molecular Pain3区 · 医学

Increased expression of Trpv1 in peripheral terminals mediates thermal nociception in Fabry disease mouse model

3区 · 医学

ArticleOA

作者: Liguori, Rocco ; Lakomá, Jarmila ; Donadio, Vincenzo ; Rimondini, Roberto ; Ferrer Montiel, Antonio ; Caprini, Marco

Fabry disease is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (α-GalA) enzyme. α-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3) in the endothelium and vascular smooth muscles. A hallmark symptom of Fabry disease patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. The α-GalA gene null mouse model (α-GalA(−/0)) has provided molecular evidence for the molecular alterations in small type-C nociceptors in Fabry disease that may underlie their hyperexcitability, although the specific mechanism remains elusive. Here, we have addressed this question and report that small type-C nociceptors from α-GalA(−/0) mice exhibit a significant increase in the expression and function of the TRPV1 channel, a thermoTRP channel implicated in painful heat sensation. Notably, male α-GalA(−/0) mice displayed a ≈2-fold higher heat sensitivity than wild-type animals, consistent with the augmented expression levels and activity of TRPV1 in α-GalA(−/0) nociceptors. Intriguingly, blockade of neuronal exocytosis with peptide DD04107, a process that inhibits among others the algesic membrane recruitment of TRPV1 channels in peptidergic nociceptors, virtually eliminated the enhanced heat nociception of α-GalA(−/0) mice. Together, these findings suggest that the augmented expression of TRPV1 in α-GalA(−/0) nociceptors may underly at least in part their increased heat sensitivity, and imply that blockade of peripheral neuronal exocytosis may be a valuable pharmacological strategy to reduce pain in Fabry disease patients, increasing their quality of life.

2012-06-01·Journal of Pharmacology and Experimental Therapeutics3区 · 医学

An Inhibitor of Neuronal Exocytosis (DD04107) Displays Long-Lasting In Vivo Activity against Chronic Inflammatory and Neuropathic Pain

3区 · 医学

Article

作者: Ferrer-Montiel, Antonio ; Valenzuela, Belen ; Fernandez, Jimena ; Barros, Francisco ; Veretchy, Mario ; Baamonde, Ana ; Di Serio, Stefano ; de la Pena, Pilar ; Ponsati, Berta ; Carreno, Cristina ; Beltran, Beatriz ; Menendez, Luis ; Duart, Maria Jose ; Planells-Cases, Rosa ; Borsini, Franco ; Curto-Reyes, Verdad ; Felipo, Vicente ; Cauli, Omar ; Borges, Ricardo ; Caprioli, Antonio ; Van Den Nest, Wim

Small peptides patterned after the N terminus of the synaptosomal protein of 25 kDa, a member of the protein complex implicated in Ca(2+)-dependent neuronal exocytosis, inhibit in vitro the release of neuromodulators involved in pain signaling, suggesting an in vivo analgesic activity. Here, we report that compound DD04107 (palmitoyl-EEMQRR-NH(2)), a 6-mer palmitoylated peptide that blocks the inflammatory recruitment of ion channels to the plasma membrane of nociceptors and the release of calcitonin gene-related peptide from primary sensory neurons, displays potent and long-lasting in vivo antihyperalgesia and antiallodynia in chronic models of inflammatory and neuropathic pain, such as the complete Freund's adjuvant, osteosarcoma, chemotherapy, and diabetic neuropathic models. Subcutaneous administration of the peptide produced a dose-dependent antihyperalgesic and antiallodynic activity that lasted ≥24 h. The compound showed a systemic distribution, characterized by a bicompartmental pharmacokinetic profile. Safety pharmacology studies indicated that the peptide is largely devoid of side effects and substantiated that the in vivo activity is not caused by locomotor impairment. Therefore, DD04107 is a potent and long-lasting antinociceptive compound that displays a safe pharmacological profile. These findings support the notion that neuronal exocytosis of receptors and neuronal algogens pivotally contribute to chronic inflammatory and neuropathic pain and imply a central role of peptidergic nociceptor sensitization to the pathogenesis of pain.

100 项与 Parentide 相关的药物交易

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