Sigma receptor
Sigma receptors (σRs) have been recently referred in cancer pathophysiology. Three types of the opiate receptors were suggested and named by the corresponding greek symbol: μ for morphine, κ for ketazocine, and σ for (±)-SKF-10,047. Originally, two types of sigma receptors (σRs) were identified, sigma 1 receptor (σ1R), which was first cloned in 1996, and sigma 2 receptor (σ2R), which has not been cloned yet. One more type has been suggested, sigma 3 (σ3R), but it has not been defined adequately. σ1R is a polypeptide of molecular weight (MW) 29 kDa that comprises 223 amino acids and is not similar to known receptors, except for a 66.4% homology with a yeast C8-C7 sterol isomerase, they are important for the modulation of cation channels (K+, Na+ and Ca2+). σ1Rs are intracellular receptors that can translocate inside cells and act as chaperone proteins. Chaperone proteins are responsible for the correct folding of other proteins, during their synthesis or function. σ1Rs regulate Ca2+ signaling via the inositol triphosphate [IP3] receptor and, in particular, they ensure the Ca2+ signaling from endoplasmic reticulum (ER) into mitochondrion. Moreover, σ1Rs modulate K+ channels in pituitary and brain cells through G protein coupling or protein-protein interactions.
The cell shrinkage, which is necessary for programmed cell death (apoptosis), is mediated through K+ loss. Moreover, σ1R is assumed to be involved in tumor genesis, as the corresponding receptor gene is a target of the oncogene c-Myc. The σ2 protein was initially characterized as the progesterone receptor membrane component 1 (PGRMC1). In contrast to σ1Rs that dynamically translocate, σ2Rs are located in the lipid raft and are coupled with the PGRMC1 complex, EGFR, mTOR, caspases, and various ion channels. σ1R and σ2R have recently been involved in apoptosis (programmed cell death). σ1R and σ2R are highly expressed in cancer cells and up-regulated prior to mitosis, suggesting important cellular functions in cancer. σ1R antagonists deactivate the receptor activity, which is anti-apoptotic and neuroprotective and σ2R agonists stimulate the receptor activity and sensitizes cancer cells for apoptosis. Although there is considerable evidence of antiproliferative and cytotoxic activity for σ1R antagonists, σ2R agonists and mixed σ1R/σ2R ligands, the mechanism of action is still elusive.
References
1.Georgiadis MO,et al. Molecules. 2017;22(9):1408.
The cell shrinkage, which is necessary for programmed cell death (apoptosis), is mediated through K+ loss. Moreover, σ1R is assumed to be involved in tumor genesis, as the corresponding receptor gene is a target of the oncogene c-Myc. The σ2 protein was initially characterized as the progesterone receptor membrane component 1 (PGRMC1). In contrast to σ1Rs that dynamically translocate, σ2Rs are located in the lipid raft and are coupled with the PGRMC1 complex, EGFR, mTOR, caspases, and various ion channels. σ1R and σ2R have recently been involved in apoptosis (programmed cell death). σ1R and σ2R are highly expressed in cancer cells and up-regulated prior to mitosis, suggesting important cellular functions in cancer. σ1R antagonists deactivate the receptor activity, which is anti-apoptotic and neuroprotective and σ2R agonists stimulate the receptor activity and sensitizes cancer cells for apoptosis. Although there is considerable evidence of antiproliferative and cytotoxic activity for σ1R antagonists, σ2R agonists and mixed σ1R/σ2R ligands, the mechanism of action is still elusive.
References
1.Georgiadis MO,et al. Molecules. 2017;22(9):1408.
Autophagy
Sigma receptor
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KSK67
产品货号 : M36971
cas no: 2566715-93-1
KSK67 是一种高亲和力双重 sigma-2 和 组胺 H3 受体拮抗剂,对 H3 受体、sigma-1、sigma-2 受体的 Ki 分别为 3.2, 1531, 101 nM。KSK67 可用于伤害性疼痛和神经性疼痛的研究。 -
S1R agonist 2
产品货号 : M36422
cas no: 150085-21-5
S1R agonist 2 (Compound 8b) 是一种选择性 S1R 激动剂,对 S1R 和 S2R 的 Ki 分别为 1.1 nM 和 88 nM。S1R agonist 2 对 ROS 和 NMDA 诱导的神经毒性具有神经保护作用。 -
BMY-14802
产品货号 : M35949
cas no: 105565-56-8
BMY 14802 是一种 sigma-1 受体 (σ1R) 的拮抗剂,也是血清素 1A 受体 (5-HT 1A Receptor) 和肾上腺素能受体 alpha-1 (α-1 adrenergic receptor) 的激动剂。 BMY 14802 在大鼠帕金森病 (PD) 模型中可抑制异常不自主运动 (AIM),并下调 AIM 的表达。 -
KB-5492 free base
产品货号 : M35637
cas no: 113594-64-2
KB-5492 free base 是一种有效的和选择性的 sigma 受体抑制剂,抑制 [3H]1,3-di(2-tolyl)guanidine (DTG) 与 sigma 受体结合,IC50 值为 3.15 μM。KB-5492 free base 是一种抗溃疡剂。 -
Opipramol
产品货号 : M35552
cas no: 315-72-0
Opipramol (Ensidon) 是一种非典型的三环类抗抑郁试剂 (TCA)。Opipramol 主要用作 sigma (σ) 受体激动剂,可以有效地与 sigma 识别位点相互作用,Ki 值为 50 nM。Opipramol 可用于广泛性焦虑症(GAD)的研究。