Sigma 2 Receptor
Sigma-2 receptor (σ2R), identified as TMEM97, is an endoplasmic-reticulum transmembrane protein linked to cancer biology, NPC1 interaction, and sterol-related regulation[1]. Mechanistically, TMEM97 cooperates with PGRMC1 and LDLR to form a ternary complex that increases LDL internalization, placing σ2R research in cholesterol trafficking and membrane-transport studies[2]. In Alzheimer-related models, the TMEM97-PGRMC1-LDLR complex mediates cellular uptake of Aβ42 and its aggregates, supporting its use in amyloid-uptake experiments[3]. In tumor models, σ2R expression tracks proliferative status in solid tumors, making it useful for proliferation-focused oncology research[4]. Compared with σ1R, σ2R/TMEM97 requires subtype-selective ligand validation, because classical DTG binding can overlap with σ1R assays[5]. For experimental design, TMEM97 or PGRMC1 knockout did not change sigma-2 ligand-induced cytotoxic EC50 values in HeLa cells, so cytotoxicity should not be assigned automatically to either protein[5]. For imaging applications,[^18F]ISO-1 PET uptake has been evaluated as a marker of breast-cancer proliferation, linking σ2R ligands to translational tumor-imaging studies[6]. Recent cellular studies further show that sigma-2 receptor ligand binding modulates the association between TSPO and TMEM97, expanding mechanistic assays beyond PGRMC1-centered models[7].
References:
- [1]. Alon A, et al. Identification of the gene that codes for the σ2 receptor. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7160-7165. [Content Brief]
- [2]. Riad A, et al. Sigma-2 Receptor/TMEM97 and PGRMC-1 Increase the Rate of Internalization of LDL by LDL Receptor through the Formation of a Ternary Complex. Sci Rep. 2018 Nov 15;8(1):16845. [Content Brief]
- [3]. Riad A, et al. The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates. Mol Neurobiol. 2020 Sep;57(9):3803-3813. [Content Brief]
- [4]. Wheeler KT, et al. Sigma-2 receptors as a biomarker of proliferation in solid tumours. Br J Cancer. 2000 Mar;82(6):1223-32. [Content Brief]
- [5]. Zeng C, et al. TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death. Cell Death Discov. 2019 Jan 28;5:58. [Content Brief]
- [6]. McDonald ES, et al. Breast Cancer 18F-ISO-1 Uptake as a Marker of Proliferation Status. J Nucl Med. 2020 May;61(5):665-670. [Content Brief]
- [7]. Thejer BM, et al. Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97. Int J Mol Sci. 2023 Mar 28;24(7):6381. [Content Brief]
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Sigma 2 Receptor Related Products (34)
Related Products (34)
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Sigma-2 Receptor ligand 1
0 ImagesCat. No.: HY-174155Sigma-2 Receptor ligand 1 (Compound 7i) is a highly selective Sigma-2 receptor ligand with a Ki value of 40 nM. Sigma-2 Receptor ligand 1 is promising for research of Alzheimer's disease.
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BS148
0 ImagesCat. No.: HY-121033CAS No.: 2162116-09-6BS148 is a selective sigma-2 receptor (S2R) agonist with a Ki 20 nM. BS148 shows >80-fold selective for S2R than S1R. BS148 activates the endoplasmic reticulum stress response through the upregulation of protein kinase R-like ER kinase (PERK), activating transcription factor 4 (ATF4) genes, and C/EBP homologous protein (CHOP). BS148 induces apoptosis in melanoma cell. BS148 downregulates genes related to the cholesterol pathway and activates the MAPK signaling pathway. BS148 can be used for the study of melanoma.
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CM764
0 ImagesCat. No.: HY-117420CAS No.: 1350296-29-5CM764 is an activator for sigma receptor with Ki of 86.6 and 3.5 nM for sigma-1 receptor and sigma-2 receptor. CM764 increases cytoplasmic calcium, NAD+/NADH, and ATP levels, and decreases the concentration of ROS.
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CB-64D
0 ImagesCat. No.: HY-120360CAS No.: 157752-20-0CB-64D is the agonist for sigma receptor 2 and sigma receptor 1 with Ki of 16.5 and 3063 nM. CB-64D induces apoptosis in cancer cell SK-N-SH.
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AB21
0 ImagesCat. No.: HY-149854CAS No.: 3026677-23-3AB21 is a potent and selective S1R antagonist with Kis of 13, 102 nM for S1R and S2R. AB21 has the effect of reducing mechanical hypersensitivity.
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MS-377
0 ImagesCat. No.: HY-120155CAS No.: 206862-30-8MS-377 is a selective and orally active sigma-1 receptor ligand (Ki=73 nM) with weak affinity for sigma-2 receptor (Ki=6900 nM) and no affinity for any other receptors including dopamine, serotonin, PCP site, glutamate, γ-aminobutylic acid, adenosine, adrenergic receptors, etc. (Ki: >10 μM). MS-377 indirectly modulates the NMDA receptor ion-channel complex. MS-377 is a antipsychotic agent. MS-377 inhibits PCP-induced behaviors by inhibition of the increase in dopamine and serotonin release in the rat medial prefrontal cortex. MS-377 can be used for research of schizophrenia.
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KOR agonist 7
0 ImagesCat. No.: HY-178945KOR agonist 7 (Compound 29) is a highly selective κ-opioid receptor (KOR) agonist with a Ki of 138 nM. KOR agonist 7 shows no activity at μ- and δ-opioid receptors or σ1 receptor, and exhibits extremely low affinity for σ2 receptor (Ki = 2.8 μM). KOR agonist 7 significantly reduces the secretion of pro-inflammatory cytokines such as IL-6, TNF-α, and IFN-γ, while increasing the production of the anti-inflammatory cytokine IL-10. KOR agonist 7 downregulates the expression of the pro-inflammatory M1 macrophage marker CD80 and upregulates the anti-inflammatory M2 macrophage marker CD163. KOR agonist 7 holds potential for applications in analgesia and immune modulation.
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SW116 free base
0 ImagesCat. No.: HY-120421CAS No.: 1036759-00-8SW116 free base is a selective fluorescent ligand for sigma-2 receptor with a Ki of 14 nM. SW116 free base exhibits in methanol a maximal excitation wavelength of 333 nM, and a maximal emission wavelength of 506 nM. SW116 free base can be internalized into MDA-MB-435 cells, and reach 50% maximum fluorescent intensity in 24 minutes. SW116 free base can be as a fluorescent probe used in cancer research.
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KSCM-1
0 ImagesCat. No.: HY-118279CAS No.: 1415247-17-4KSCM-1 is a selective sigma-1 receptor ligand with a Ki of 27.5 nM. KSCM-1 shows more selective for sigma-1 over sigma-2, and shows no significant affinity at non-sigma receptors.
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Convolamine hydrochloride
0 ImagesCat. No.: HY-N15339ACAS No.: 5896-59-3Convolamine hydrochloride is a tropane alkaloid and a potent Sigma-1 receptor positive allosteric modulator with an IC50 value of 289 nM. Convolamine hydrochloride can be extracted from Convolvulus plauricalis. Convolamine hydrochloride exhibits cognitive-improving and neuroprotective properties. Convolamine hydrochloride can be used in research related to Wolfram syndrome and Alzheimer's disease.
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RTI-371
0 ImagesCat. No.: HY-129215CAS No.: 652978-45-5RTI-371 is a highly selective atypical dopamine transporter (DAT) inhibitor that crosses the blood-brain barrier. RTI-371 exhibits potent inhibitory activity in cell lines transfected with human DAT (IC50 = 8.7 nM) and shows high binding affinity for rat DAT with a Ki value of 7.81 nM. RTI-371 also acts as a positive allosteric modulator of the human cannabinoid 1 receptor (hCB1 receptor), enhancing the activity of cannabinoid receptor agonists in a concentration-dependent manner. RTI-371 can be used for the research of Parkinson's disease.
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σ1 Receptor antagonist 4
0 ImagesCat. No.: HY-108513CAS No.: 362512-81-0σ1 Receptor antagonist 4 (compound TC1) is a selective sigma1 (σ1) receptor antagonist with a Ki of 10 nM. σ1 Receptor antagonist 4 is weakly active at σ2 receptor (Ki of 370 nM) and has no activity at dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters.
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