(2R,3S)-E1R (Compound 2c) is an enantiomer of E1R. (2R,3S)-E1R is a sigma-1 receptor positive allosteric modulator (Sig1R PAM) for the treatment of cognition/memory disorders[1].
WLB-89462 (Compound 20c) is a selective σ2 receptor ligand (Ki: 13 nM). WLB-89462 has neuroprotective activity. WLB-89462 improves short-term memory impairment induced by Aβ peptide in rats. WLB-89462 has good ADMET profile (good solubility, no CYP inhibition, good metabolic stability, high permeability, brain penetration, and high oral exposure in rodents)[1].
PD 144418 is a highly affinity, potent and selective sigma 1 (σ1) receptor ligand (Ki values of 0.08 nM and 1377 nM for σ1 and σ2 respectively), devoid of any significant affinity for other receptors, ion channels and enzymes. PD 144418 shows potential antipsychotic activity[1][2].
SA4503(AGY-94806; Cutamesine) is a selective sigma 1 receptor(σ1R) agonist; high affinity for the sigma 1 receptor subtype labeled by (+)-[3H]pentazocine (IC50 = 17.4 +/- 1.9 nM); 100-fold less affinity for the sigma 2 receptor.IC50 value: 17.4 nM [1]Target: σ1R agonistin vitro: SA4503 showed little affinity for 36 other receptors, ion channels and second messenger systems. SA4503 significantly increased the KD value, but did not affect the Bmax value for specific (+)-[3H]pentazocine binding. SA4503 is a potent and selective agonist for the sigma 1 receptor subtype in the brain [1]. At concentrations of 1-10μM, SA4503 reduced SOD1(G93A)-induced cell death in a concentration-dependent manner [3].in vivo: The intravenous administration of SA4503 (0.01-1.28 mg/kg) did not significantly alter the firing rate or pattern of spontaneously active DA neurons in either the SNC or VTA. A single injection of either 0.1 or 0.3 mg/kg i.p. of SA4503 did not alter the number of spontaneously active SNC and VTA DA neurons. In contrast, a single injection of 1 mg/kg i.p. of SA4503 produced a significant decrease and increase in the number of spontaneously active SNC and VTA DA neurons, respectively[2]. SA4503 suppressed the progression of ALS in an SOD1(G93A) ALS mouse model. SA4503 did not affect the onset time of ALS. However, it significantly extended the survival time in the SOD1(G93A) mice compared with a vehicle-treated group [3].
(+)-Igmesine hydrochloride (JO1784) is an orally active and selective σ receptor ligand with neuroprotective and anti-amnesic activities[1].
BD1063 dhydrochloride is a potent and selective sigma 1 receptor antagonist.
Cutamesine dihydrochloride (SA4503 dihydrochloride) is a potent Sigma 1 receptor agonist with an IC50 of 17.4 nM in guinea pig brain membranes.
S1R agonist 1 (Compound 6b) is a selective S1R agonist with Kis of 0.93 nM and 72 nM for S1R and S2R, respectively. S1R agonist 1 exhibits neuroprotection against ROS and NMDA-induced neurotoxicity[1].
SOMCL-668 is a selective and potent sigma-1 receptor allosteric modulator. ?SOMCL-668 shows positive modulation of improvement in social deficits and cognitive impairment induced by the selective sigma-1 agonist PRE084.?SOMCL-668 displays anti-seizure activities and can be used for psychotic illness research[1].
S1R agonist 2 (Compound 8b) is a selective S1R agonist with Kis of 1.1 nM and 88 nM for S1R and S2R, respectively. S1R agonist 2 exhibits neuroprotection against ROS and NMDA-induced neurotoxicity[1].
BMY 14802 is a sigma-1 receptor (σ1R) antagonist, as well as an agonist at serotonin (5-HT) 1A and adrenergic alpha-1 receptors. BMY 14802 inhibits abnormal involuntary movement (AIM) in rat Parkinson's disease (PD) model, with down-regulating the expression of AIM[1][2].
BD-1047 dihydrobromide is a selective functional antagonist of sigma receptors, shows antipsychotic activity in animal models predictive of efficacy in schizophrenia. IC50 value: Target: sigma receptorin vitro: Moreover, Progesterone and BD 1047 (a sigma 1 receptor antagonist) counteracted the antidepressant-like effect induced by co-administration of Pramipexole and Sertraline (but not Pramipexole and Fluoxetine). [2] This increased pNR1 expression is significantly reduced by pretreatment with the specific Sig-1 R antagonist, BD-1047. In another set of experiments Sig-1 R agonists further potentiated NMDA-induced pain behaviour and pNR1 immunoreactivity and this is also reversed with BD-1047. [3]in vivo: BD 1047 does not decrease amphetamine-induced hyperactivity in mice in a statistically significant manner. BD 1047 does not modify the hyperactivity induced by NMDA receptor antagonists. BD 1047 shows a moderate activity in models used in this study suggesting that its usefulness as an antipsychtic drug is doubtful. [1]
BMY-14802 hydrochloride (BMY-14802-1) is a selective and orally active sigma receptor antagonist with an IC50 of 112 nM. BMY-14802 hydrochloride is also a 5-HT1A and adrenergic α1 receptors agonist. BMY-14802 hydrochloride has antipsychotic effects[1][2][3].
IPAG is a potent sigma-1 receptor antagonist with a pKi of 4.3[1]. IPAG induces apoptosis[2].
SR-31747 is a sigma ligand with immunosuppressive and anti-inflammatory properties. SR-31747 blocks cell proliferation by inhibiting sterol isomerase[1][2].
Blonanserin dihydrochloride is a potent and orally active 5-HT2A and dopamine D2 receptor antagonist, with Ki values of 0.812 and 0.142 nM, respectively. Blonanserin dihydrochloride is usually acts as an atypical antipsychotic agent, and can be used for the research of extrapyramidal symptoms, excessive sedation, or hypotension[1][2].
Sigma-2 receptor antagonist 1 is a sigma-2 (σ-2) receptor antagonist.
Sigma-LIGAND-1 is a selective sigma receptor ligand, has receptor IC50s of 16 nM at the DTG site, 19 nM at the PPP site, and a Ki of 4000 nM at the dopamine D2 receptor.
Siramesine(Lu 28-179) Hcl is a selective sigma-2 receptor agonist, which has been shown to trigger cell death of cancer cells and to exhibit a potent anticancer activity in vivo. IC50 value:Target: sigma-2 receptor; lysosome-destabilizing agentsiramesine can induce rapid cell death in a number of cell lines at concentrations above 20 μM. In HaCaT cells, cell death was accompanied by caspase activation, rapid loss of mitochondrial membrane potential (MMP), cytochrome c release, cardiolipin peroxidation and typical apoptotic morphology, whereas in U-87MG cells most apoptotic hallmarks were not notable, although MMP was rapidly lost [1]. Siramesine, a sigma-2 receptor agonist originally developed as an anti-depressant, can induce cell death in transformed cells through a mechanism involving lysosomal destabilization [2].in vivo: SA4503 or siramesine given jointly with MEM (as well as with AMA) decreased the immobility time in rats. The effect of SA4503 and AMA co-administration was antagonized by progesterone, a sigma1 receptor antagonistic neurosteroid. Combined treatment with siramesine and AMA was modified by neither progesterone nor BD1047 (a novel sigma antagonist with preferential affinity for sigma1 sites) [3]
4-PPBP maleate is a potent σ 1 receptor ligand and agonist. 4-PPBP maleate is a non-competitive, selective NR1a/2B NMDA receptors (expressed in Xenopus oocytes) antagonist. 4-PPBP maleate provides neuroprotection[1][2][3].
Noscapine is an orally administrable drug used worldwide for cough suppression, primarily mediated by its σ-receptor agonist activity, and possess anticancer activity.Target: σ-receptorin vitro: Noscapine is a phthalideisoquinoline alkaloid from opium, is a recently discovered anticancer drug and is currently under investigation in phase-I/II clinical trials for the treatment of leukemia and lymphoma. Noscapine causes few or no side effects and has been widely used as a cough suppressant in developing countries. Noscapine has been demonstrated to interact with microtubules. Interestingly, unlike many other microtubule-targeting agents such as Paclitaxel and Nocodazole, Noscapine does not obviously affect the total amount of microtubule polymers in cells; instead, it significantly increases the time microtubules spend in the pause state. The alteration of microtubule dynamics then activates the spindle checkpoint and arrests cell cycle progression at mitosis, leading to apoptotic cell death.
Rimcazole (BW 234U) dihydrochloride is a carbazole derivative that acts in part as a sigma (σ) receptor antagonist. Rimcazole dihydrochloride also binds with moderate affinity to the dopamine transporter and inhibit dopamine uptake. Rimcazole dihydrochloride can attenuate cocaine-induced locomotor activity and sensitization. Rimcazole dihydrochloride also can be used for the research of cancer[1][2][3][4].
Panamesine (EMD 57445) is a sigma receptor ligand, which has a high affinity (IC50 6 nM) and selectivity for sigma binding sites. Panamesine is a potential atypical neuroleptic agent[1].
σ1 Receptor antagonist-1 is a highly potent and selective sigma 1 receptor antagonist (pKi=10.28). σ1 Receptor antagonist-1 inhibits cell growth, arrests cell cycle at G0/G1 phase and induces apoptosis of MCF-7/ADR cells[1].
KB-5492 free base is a potent and selective inhibitor of sigma receptor, inhibits specific [3H]1,3-di(2-tolyl)guanidine (DTG) binding to the sigma receptor with an IC50 of 3.15 μM. KB-5492 free base is an anti-ulcer agent[1][2].
Siramesine(Lu 28-179) is a selective sigma-2 receptor agonist, which has been shown to trigger cell death of cancer cells and to exhibit a potent anticancer activity in vivo. IC50 value:Target: sigma-2 receptor; lysosome-destabilizing agentsiramesine can induce rapid cell death in a number of cell lines at concentrations above 20 μM. In HaCaT cells, cell death was accompanied by caspase activation, rapid loss of mitochondrial membrane potential (MMP), cytochrome c release, cardiolipin peroxidation and typical apoptotic morphology, whereas in U-87MG cells most apoptotic hallmarks were not notable, although MMP was rapidly lost [1]. Siramesine, a sigma-2 receptor agonist originally developed as an anti-depressant, can induce cell death in transformed cells through a mechanism involving lysosomal destabilization [2].in vivo: SA4503 or siramesine given jointly with MEM (as well as with AMA) decreased the immobility time in rats. The effect of SA4503 and AMA co-administration was antagonized by progesterone, a sigma1 receptor antagonistic neurosteroid. Combined treatment with siramesine and AMA was modified by neither progesterone nor BD1047 (a novel sigma antagonist with preferential affinity for sigma1 sites) [3]
PD 144418 oxalate is a highly affinity, potent and selective sigma 1 (σ1) receptor ligand (Ki values of 0.08 nM and 1377 nM for σ1 and σ2 respectively). PD 144418 oxalate devoids of any significant affinity for other receptors, ion channels and enzymes. PD 144418 oxalate shows potential antipsychotic activity[1][2].
OPC-14523 hydrochloride is an orally active sigma and 5-HT1A receptor agonist, with high affinity for sigma receptors (σ1/2 IC50=47/56 nM), the 5-HT1A receptor (IC50=2.3 nM), and the 5-HT transporter (IC50=80 nM). OPC-14523 hydrochloride shows antidepressant-like activity[1][2].
OPC-14523 free base is an orally active sigma and 5-HT1A receptor agonist, with high affinity for sigma receptors (σ1/2 IC50=47/56 nM), the 5-HT1A receptor (IC50=2.3 nM), and the 5-HT transporter (IC50=80 nM). OPC-14523 free base shows antidepressant-like activity[1][2].
AVex-73 hydrochloride is a Sigma-1 Receptor agonist with an IC50 of 860 nM.