Delving into the Latest Updates on RC-3095 with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms

Target

GRPR

Mechanism

GRPR antagonists(Gastrin releasing peptide receptor antagonists)

Therapeutic Areas

NeoplasmsRespiratory DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

NeoplasmsProstatic CancerSmall Cell Lung Cancer+ [1]

Originator Organization

Tulane University Hospital & Clinic

Active Organization-

Inactive Organization

AEterna Zentaris GmbH

Æterna Zentaris, Inc.

Tulane University Hospital & Clinic

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC56H79N15O9

InChIKeyIUYCRRDHLJIJBB-QAGBKCHLSA-N

CAS Registry138147-78-1

Gene Sequence

Sequence Code 13890089

BackgroundUremic pruritus is a prevalent clinical symptom in maintenance dialysis patients. Existing evidence establishes a connection between itch transmission and the gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway.ObjectiveTo investigate the involvement of the gastrin-releasing peptide/gastrin-releasing peptide receptor in itch sensation signaling within the spinal cord of uremic pruritus.DesignAn animal study was conducted.SettingThe research was conducted at the First Hospital of Hebei Medical University.ParticipantsA total of 50 male C57BL/6J mice (weight: 30-40 g) were acquired from Beijing Weitonglihua Laboratory Animal Center.InterventionsMice were categorized into five groups: normal, sham, Y, A, and B. The Y group received intrathecal injections of saline (5 ul). The A group received intrathecal injections of gastrin-releasing peptide (0.1 nmol, 5 ul), and the B group received intrathecal injections of the gastrin-releasing peptide receptor antagonist RC-3095 (0.3 mmol, 5 ul).Primary Outcome Measures(1) Pruritus behavior of mice and (2) expression of gastrin-releasing peptide, gastrin-releasing peptide receptor, and inositol trisphosphate.ResultsScratching times in the Y group significantly surpassed those of normal and sham groups, increasing over time. Gastrin-releasing peptide and receptor expression rose in the uremic pruritus mouse model compared to normal and sham groups (P < .05). Expression of gastrin-releasing peptide and its receptor was significantly elevated in the uremic pruritus mouse model compared to the normal and sham groups (P < .05). Inositol trisphosphate expression in the dorsal spinal horn of Y group mice increased compared to normal and sham groups. Intrathecal gastrin-releasing peptide heightened inositol trisphosphate expression, while the peptide receptor antagonist RC-3095 reduced it. Y group scratching times were higher than normal and sham groups, increasing after intrathecal gastrin-releasing peptide but decreasing after RC-3095 injection.ConclusionThe gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway is involved in the development of uremic pruritus.

18 Apr 2024·Alternative therapies in health and medicine

Gastrin-Releasing Peptide/Gastrin-Releasing Peptide Receptor Participation in Itch Sensation Signaling in the Spinal Cord of Uremic Pruritus Mice.

Article

Author: Du, Liang ; Zhang, Ze ; Chen, Hao ; Li, Huili ; Wang, Yitong ; Gao, Weiwei

BackgroundUremic pruritus is a prevalent clinical symptom in maintenance dialysis patients. Existing evidence establishes a connection between itch transmission and the gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway.ObjectiveTo investigate the involvement of the gastrin-releasing peptide/gastrin-releasing peptide receptor in itch sensation signaling within the spinal cord of uremic pruritus.DesignAn animal study was conducted.SettingThe research was conducted at the First Hospital of Hebei Medical University.ParticipantsA total of 50 male C57BL/6J mice (weight: 30-40 g) were acquired from Beijing Weitonglihua Laboratory Animal Center.InterventionsMice were categorized into five groups: normal, sham, Y, A, and B. The Y group received intrathecal injections of saline (5 ul). The A group received intrathecal injections of gastrin-releasing peptide (0.1 nmol, 5 ul), and the B group received intrathecal injections of the gastrin-releasing peptide receptor antagonist RC-3095 (0.3 mmol, 5 ul).Primary Outcome Measures(1) Pruritus behavior of mice and (2) expression of gastrin-releasing peptide, gastrin-releasing peptide receptor, and inositol trisphosphate.ResultsScratching times in the Y group significantly surpassed those of normal and sham groups, increasing over time. Gastrin-releasing peptide and receptor expression rose in the uremic pruritus mouse model compared to normal and sham groups (P < .05). Expression of gastrin-releasing peptide and its receptor was significantly elevated in the uremic pruritus mouse model compared to the normal and sham groups (P < .05). Inositol trisphosphate expression in the dorsal spinal horn of Y group mice increased compared to normal and sham groups. Intrathecal gastrin-releasing peptide heightened inositol trisphosphate expression, while the peptide receptor antagonist RC-3095 reduced it. Y group scratching times were higher than normal and sham groups, increasing after intrathecal gastrin-releasing peptide but decreasing after RC-3095 injection.ConclusionThe gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway is involved in the development of uremic pruritus.

01 Nov 2021·Translational OncologyQ3 · MEDICINE

Blocking GRP/GRP-R signaling decreases expression of androgen receptor splice variants and inhibits tumor growth in castration-resistant prostate cancer

Q3 · MEDICINE

ArticleOA

Author: Sterling, Julie A ; Merkel, Alyssa ; Liu, Qi ; Jin, Renjie ; Ramirez-Solano, Marisol ; Case, Thomas C

Clinical management of castration-resistant prostate cancer (CRPC) resulting from androgen deprivation therapy (ADT) remains challenging. Many studies indicate that androgen receptor splice variants (ARVs) play a critical role in the development of CRPC, including resistance to the new generation of inhibitors of androgen receptor (AR) action. ARVs are constitutively active and lack the ligand-binding domain (LBD), thereby allowing prostate cancer (PC) to maintain AR activity despite therapies that target the AR (full-length AR; AR-FL). Previously, we have reported that long-term ADT increases the neuroendocrine (NE) hormone - Gastrin Releasing Peptide (GRP) and its receptor (GRP-R) expression in PC cells. Further, we demonstrated that activation of GRP/GRP-R signaling increases ARVs expression by activating NF-κB signaling, thereby promoting cancer progression to CRPC. Most importantly, as a cell surface protein, GRP-R is easily targeted by drugs to block GRP/GRP-R signaling. In this study, we tested if blocking GRP/GRP-R signaling by targeting GRP-R using GRP-R antagonist is sufficient to control CRPC progression. Our studies show that blocking GRP/GRP-R signaling by targeting GRP-R using RC-3095, a selective GRP-R antagonist, efficiently inhibits NF-κB activity and ARVs (AR-V7) expression in CRPC and therapy-induced NEPC (tNEPC) cells. In addition, blocking of GRP/GRP-R signaling by targeting GRP-R can sensitize CRPC cells to anti-androgen treatment (such as MDV3100). Further, preclinical animal studies indicate combination of GRP-R antagonist (targeting ARVs) with anti-androgen (targeting AR-FL) is sufficient to inhibit CRPC and tNEPC tumor growth.

100 Deals associated with RC-3095

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 2	US	Æterna Zentaris, Inc.	-
Prostatic Cancer	Phase 2	-	AEterna Zentaris GmbH	-
Prostatic Cancer	Phase 2	-	Tulane University Hospital & Clinic	-
Small Cell Lung Cancer	Phase 2	-	AEterna Zentaris GmbH	-
Small Cell Lung Cancer	Phase 2	-	Tulane University Hospital & Clinic	-
Solid tumor	Phase 2	BR	Æterna Zentaris, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EULAR2013	Not Applicable	gastrin-releasing peptide \| gastrin-releasing peptide receptor	-	RC-3095	iatkdrltaz(sxoxuuxzem) = perqklojna sqoamrkwbg (cwqekckczk )	-	12 Jun 2013
				RC-3095	iatkdrltaz(sxoxuuxzem) = lkcvvltkdd sqoamrkwbg (cwqekckczk ) View more