Last update 01 Nov 2024

PGRMC1 x σ1 receptor

Last update 01 Nov 2024

Basic Info

Related Targets

PGRMC1σ1 receptor

Drugs associated with PGRMC1 x σ1 receptor

SAS-0132

Target

PGRMC1 x σ1 receptor

Mechanism

PGRMC1 antagonists [+1]

Active Org.

Stanford University [+1]

Originator Org.

Stanford University

Active Indication

Alzheimer Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PGRMC1 x σ1 receptor

100 Translational Medicine associated with PGRMC1 x σ1 receptor

0 Patents (Medical) associated with PGRMC1 x σ1 receptor

Literatures (Medical) associated with PGRMC1 x σ1 receptor

17 Mar 2016·ChemMedChemQ3 · MEDICINE

Norbenzomorphan Framework as a Novel Scaffold for Generating Sigma 2 Receptor/PGRMC1 Subtype‐Selective Ligands

Q3 · MEDICINE

Article

Author: Chan, Jessica Z. ; Hodges, Timothy R. ; Sahn, James J. ; Martin, Stephen F.

AbstractA novel structural class with high affinity and subtype selectivity for the sigma 2 receptor has been discovered. Preliminary structure–affinity relationship data are presented showing that 8‐substituted 1,3,4,5‐tetrahydro‐1,5‐methanobenzazepine (norbenzomorphan) derivatives elicit modest to high selectivity for the sigma 2 over the sigma 1 receptor subtype. Indeed, piperazine analogue 8‐(4‐(3‐ethoxy‐3‐oxopropyl)piperazin‐1‐yl)‐1,3,4,5‐tetrahydro‐1,5‐methanobenzazepine‐2‐carboxylate (SAS‐1121) is 574‐fold selective for the sigma 2 over the sigma 1 receptor, thereby establishing it as one of the more subtype‐selective sigma 2 binding ligands reported to date. Emerging evidence has implicated the sigma 2 receptor in multiple health disorders, so the drug‐like characteristics of many of the selective sigma 2 receptor ligands disclosed herein, coupled with their structural similarity to frameworks found in known drugs, suggest that norbenzomorphan analogues may be promising candidates for further development into drug leads.

01 Nov 2015·EBioMedicineQ1 · MEDICINE

The Sigma-2 Receptor and Progesterone Receptor Membrane Component 1 are Different Binding Sites Derived From Independent Genes

Q1 · MEDICINE

ArticleOA

Author: Mavlyutov, Timur A ; Ruoho, Arnold E ; Mesangeau, Christophe ; McCurdy, Christopher R ; Chu, Ming-Liang ; Yang, Huan ; Guo, Lian-Wang ; Chu, Uyen B ; Schulman, Amanda

The sigma-2 receptor (S2R) is a potential therapeutic target for cancer and neuronal diseases. However, the identity of the S2R has remained a matter of debate. Historically, the S2R has been defined as (1) a binding site with high affinity to 1,3-di-o-tolylguanidine (DTG) and haloperidol but not to the selective sigma-1 receptor ligand (+)-pentazocine, and (2) a protein of 18-21 kDa, as shown by specific photolabeling with [(3)H]-Azido-DTG and [(125)I]-iodoazido-fenpropimorph ([(125)I]-IAF). Recently, the progesterone receptor membrane component 1 (PGRMC1), a 25 kDa protein, was reported to be the S2R (Nature Communications, 2011, 2:380). To confirm this identification, we created PGRMC1 knockout NSC34 cell lines using the CRISPR/Cas9 technology. We found that in NSC34 cells devoid of or overexpressing PGRMC1, the maximum [(3)H]-DTG binding to the S2R (Bmax) as well as the DTG-protectable [(125)I]-IAF photolabeling of the S2R were similar to those of wild-type control cells. Furthermore, the affinities of DTG and haloperidol for PGRMC1 (KI = 472 μM and 350 μM, respectively), as determined in competition with [(3)H]-progesterone, were more than 3 orders of magnitude lower than those reported for the S2R (20-80 nM). These results clarify that PGRMC1 and the S2R are distinct binding sites expressed by different genes.

01 Oct 2015·Biochimica et Biophysica Acta (BBA) - Biomembranes

Potential applications for sigma receptor ligands in cancer diagnosis and therapy

Review

Author: Rybczynska, Anna A ; van Waarde, Aren ; Dierckx, Rudi A J O ; Ishiwata, Kiichi ; Ramakrishnan, Nisha K ; Elsinga, Philip H

Sigma receptors (sigma-1 and sigma-2) represent two independent classes of proteins. Their endogenous ligands may include the hallucinogen N,N-dimethyltryptamine (DMT) and sphingolipid-derived amines which interact with sigma-1 receptors, besides steroid hormones (e.g., progesterone) which bind to both sigma receptor subpopulations. The sigma-1 receptor is a ligand-regulated molecular chaperone with various ion channels and G-protein-coupled membrane receptors as clients. The sigma-2 receptor was identified as the progesterone receptor membrane component 1 (PGRMC1). Although sigma receptors are over-expressed in tumors and up-regulated in rapidly dividing normal tissue, their ligands induce significant cell death only in tumor tissue. Sigma ligands may therefore be used to selectively eradicate tumors. Multiple mechanisms appear to underlie cell killing after administration of sigma ligands, and the signaling pathways are dependent both on the type of ligand and the type of tumor cell. Recent evidence suggests that the sigma-2 receptor is a potential tumor and serum biomarker for human lung cancer and an important target for inhibiting tumor invasion and cancer progression. Current radiochemical efforts are focused on the development of subtype-selective radioligands for positron emission tomography (PET) imaging. Right now, the mostpromising tracers are [18F]fluspidine and [18F]FTC-146 for sigma-1 receptors and [11C]RHM-1 and [18F]ISO-1 for the sigma-2 subtype. Nanoparticles coupled to sigma ligands have shown considerable potential for targeted delivery of antitumor drugs in animal models of cancer, but clinical studies exploring this strategy in cancer patients have not yet been reported. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis