LUF7690 (Compound 9) is a clickable and covalent affinity-based probe (AfBP) that targets the human A3AR (hA3AR). LUF7690 can be used in the detection and characterization of the hA3AR in different types of granulocytes, among other cell types[1].
(E)-Guanabenz ((E)-Wy-8678) is an orally active central α2-adrenoceptor agonist. (E)-Guanabenz has antihypertensive activity, acts via stimulating central α2-adrenoceptors, and reducing net sympathetic outflow into the periphery. (E)-Guanabenz also directly binds to and inhibits GADD34, and has neuroprotective activity. (E)-Guanabenz can be used for researching hypertension and Parkinson disease[1][2].
Scopolamine is a high affinity (nM) muscarinic antagonist. 5-HT3 receptor-responses are reversibly inhibited by Scopolamine with an IC50 of 2.09 μM.
Alarelin acetate is a synthetic GnRH agonist.
JNJ-31020028 is a selective brain penetrant antagonist of neuropeptide Y2 receptor with high affinity(pIC50=8.07, human; pIC50=8.22 rat); >100-fold selective versus human Y1/Y4/Y5 receptors.IC50 value: 8.07/8.22(human/rat pIC50) [1]Target: Y2 receptor antagonistin vitro: JNJ-31020028 was demonstrated to be an antagonist (pK(B) = 8.04 +/- 0.13) in functional assays [1].in vivo: JNJ-31020028 occupied Y(2) receptor binding sites (approximately 90% at 10 mg/kg) after subcutaneous administration in rats [1]. Neither systemic (0, 15, 30, and 40 mg/kg, subcutaneously [s.c.]) nor intracerebroventricular (0.0, 0.3, and 1.0 nmol/rat) administration of JNJ-31020028 affected alcohol-reinforced lever pressing or relapse to alcohol seeking behavior following stress exposure. JNJ-31020028 (15 mg/kg, s.c.) did reverse the anxiogenic effects of withdrawal from a single bolus dose of alcohol on the elevated plus-maze, confirming the anxiolytic-like properties of NPY Y2 antagonism [2]. Chronic administration of JNJ-31020028 induced a decrease in immobility time in the forced swim test in OBX while had no effect in control animals [3].
Halopemide is a potent phospholipase D (PLD) inhibitor, with IC50s of 220 and 310 nM for human PLD1 and PLD2, respectively. Halopemid is a dopamine receptors antagonist, and acts a psychotropic agent[1][2].
NAN-190 hydrobromide is a serotonin receptor 5-HT antagonist. NAN-190 is a selective antagonist of 5-HT1A.Target: 5-HT in vitro: NAN-190 is a 5-HT1A antagonist. [3] NAN-190 is a selective antagonist of 5-HT1A. [1]in vivo: NAN-190 (0.5 mg/kg, ip), as a 5-HT1A receptor antagonist, is injected concomitantly with the effective dose of fluoxetine. NAN-190 (5-HT1A receptor antagonist) reverses the catalepsy-improving effect of fluoxetine in 6-OHDA lesioned rats. [2]
SR 146131 is a potent, orally available, and selective nonpeptide (cholecystokinin 1) receptor agonist.
F-15599 is a highly selective G-protein biased 5-HT1A receptor agonist, with Ki of 3.4 nM.
Dolasetron Mesylate (MDL-73147) is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy.
Agomelatine hydrochloride is a antidepressant, which is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor. IC50 value: 6.2 (pKi, 5-HT2c); 6.6 (pKi, 5-HT2b)Target: 5-HT 2c receptor Agomelatine hydrochloride is an antidepressant drug. It is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor. Activation of 5-HT2C receptors by serotonin inhibits dopamine and norepinephrine release. Antagonism of 5-HT2C results in an enhancement of DA and NE release and activity of frontocortical dopaminergic and adrenergic pathways [1]. A total of 42 rats were divided into 7 groups as each composed of 6 rats: (1) intact, (2) 40 mg/kg agomelatine, (3) 140 mg/kg N-acetylcysteine (NAC), (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 20 mg/kgagomelatine, and (7) 2 g/kg paracetamol + 40 mg/kg agomelatine groups. Paracetamol-induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically. There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and 8-iso-prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol. Administration of agomelatine and NAC separately reversed these changes significantly [2].Clinical indications: Depression; Obsessive compulsive disorderFDA Approved Date: October 2011Toxicity: Hyperhidrosis; Abdominal pain; Nausea; Vomiting; Diarrhoea; Constipation; Back pain; Fatigue
SB 258719 is a selective 5-HT7 receptor antagonist with a pKi of 7.5.
Tyrphostin 8 is a tyrosine kinase, with an IC50 of 560 μM for EGFR kinase. Tyrphostin 8 is also a GTPase inhibitor. Tyrphostin 8 can inhibit the protein serine/threonine phosphatase calcineurin (IC50=21 μM)[1][2][3].
U91356 is a dopamine receptor agonist.
Relacorilant is a potent, selective and orally bioavailable glucocorticoid receptor antagonist, with a Ki of 7.2 nM in HepG2 TAT assay, and also shows Kis of 12, 81.2, 210 nM for rat, human and monkey glucocorticoid receptor in cell-based assay, respectively; Relacorilant has entered phase 2 clinical study in patients with Cushing’s syndrome.
L162441 is an Angiotensin type 1 receptor antagonist.
TRAP-6 amide TFA is a PAR-1 thrombin receptor agonist peptide[1].
4-IBP is a selective σ1 agonist with a high level of affinity for the σ1 receptor (Ki = 1.7 nM) and a moderate affinity for the σ2 receptor (Ki = 25.2 nM) .IC50 value: 1.7 nM (Ki)Target: σ1in vitro: 4-IBP is a σ1 receptor agonist, decreases the migration of human cancer cells, including glioblastoma cells. 4-IBP is used to investigate whether targeting theσ1 receptor could modify in vitro the migration rates of human cancer cells and increase the sensitivity of metastasizing human A549 NSCLC cells and infiltrating human glioblastoma cells to cytotoxic insults of either proapoptotic or proautophagic drugs.[1]in vivo: 4-IBP increases the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.[1]
Olodanrigan (EMA401) sodium is a highly selective, orally active, peripherally restricted angiotensin II type 2 receptor (AT2R) antagonist. Olodanrigan sodium is under development as a neuropathic pain therapeutic agent. Olodanrigan sodium analgesic action appears to involve inhibition of augmented AngII/AT2R induced p38 and p42/p44 MAPK activation, and hence inhibition of DRG neuron hyperexcitability and sprouting of DRG neurons[1][2][3][4].
Cevimeline (Evoxac) is a parasympathomimetic and muscarinic agonist, with particular effect on M3 receptors; used in the treatment of dry mouth associated with sjogren's syndrome.IC50 value:Target: M3 receptor
PD 168368 is a potent, competitive, and selective neuromedin B receptor (NMB-R) antagonist with the Ki of 15–45 nM[1]. PD 168368 is neuromedin B receptor (NMBR; IC50=96 nM) / gastrin-releasing peptide receptor (GRPR IC50=3500 nM) antagonist[2]. PD 168368 also is a mixed FPR1/FPR2/FPR3 agonist with EC50s of 0.57, 0.24, and 2.7 nM, respectively[3].
SCH 336 is a potent, selective, inverse and orally active CB2 agonist. SCH 336 inhibits BaF3/CB2 migration. SCH 336 significantly inhibits the migration of leukocytes in vivo. SCH 336 blocks ovalbumin-induced lung eosinophilia in mice[1].
L-368,899 is an orally active and selective OT (oxytocin ) receptor antagonist, with IC50s of 8.9 and 26 nM for uterus of rat and human, respectively. L-368,899 can cross the blood-brain barrier (BBB). L-368,899 inhibits oxytocin-stimulated uterine contractions in rats and can be used in study of preterm labor[1][2][3].
BMS-193885 (L-Lactic acid) is a potent, selective, and brain-penetrant neuropeptide Y1 receptor antagonist. BMS-193885 has a Ki value of 3.3 nM for the neuropeptide Y1 receptor, competitively acts on the neuropeptide Y binding site, and can reduce food intake and body weight through central Y1 inhibition[1].
Befetupitant is a high-affinity, nonpeptide, competitive tachykinin 1 receptor (NK1R) antagonist.
Triflupromazine hydrochloride is an antipsychotic medication, which are Dopamine D1/D2 receptor antagonists.
CP-809101 Hcl is a potent and selective 5-HT2C receptor agonist with pEC50 of 9.96/7.19/6.81 for human 5-HT2C/5-HT2B/5-HT2A receptors respectively. IC50 Value: 9.96(pEC50 for 5-HT2C); 7.19(pEC50 for 5-HT2B); 6.81(pEC50 for 5-HT2A)Target: 5-HT2C ReceptorCP-809101 is a potent, functionally selective 5-HT2C agonist that displays approximately 100% efficacy in vitro. The aim of the present studies was to assess the efficacy of a selective 5-HT2C agonist in animal models predictive of antipsychotic-like efficacy and side-effect liability. Similar to currently available antipsychotic drugs, CP-809101 dose-dependently inhibited conditioned avoidance responding (CAR, ED50 = 4.8 mg/kg, sc). CP-809101 antagonized both PCP- and d-amphetamine-induced hyperactivity with ED50 values of 2.4 and 2.9 mg/kg (sc), respectively and also reversed an apomorphine induced-deficit in prepulse inhibition. At doses up to 56 mg/kg, CP-809101 did not produce catalepsy. Thus, the present results demonstrate that the 5-HT2C agonist, CP-809101, has a pharmacological profile similar to that of the atypical antipsychotics with low extrapyramidal symptom liability. CP-809101 was inactive in two animal models of antidepressant-like activity, the forced swim test and learned helplessness.
OT-R antagonist 1 is a new potent and selective nonpeptide low molecular weight OT-R antagonist. OT-R antagonist 1 inhibits oxytocin-evoked intracellular Ca2+ mobilization (IC50 = 8 nM).IC50 value: 8 nMTarget: oxytocin receptorin vitro: OT-R antagonist 1 inhibitis IP3-Synthesis, rat OT-R (IC50=0.03 uM). [4] OT-R antagonist 1 inhibits phosphodiesterase IV with IC50 = 6.1 μM, a value about 300-fold higher than the affinity for OT-R. OT-R antagonist 1 shows a very clean selectivity profile with specific interaction with OT-R. OT-R antagonist 1 competitively inhibits binding of [3H]oxytocin and the peptide antagonist 125I-ornithine vasotocin analog to human and rat oxytocin receptor expressed in human embryonic kidney 293-EBNA or Chinese hamster ovary cells with nanomolar potency. Selectivity against vasopressin receptor subtypes is >6-fold for V1a and >350-fold for V2 and V1b. [1]in vivo: Oxytocininduced contraction of isolated rat uterine strips is blocked by OT-R antagonist 1 (pA2 = 7.82). In anesthetized nonpregnant rats, single administration of OT-R antagonist 1 by i.v. or oral routes causes dose-dependent inhibition of contractions elicited by repeated injections of oxytocin with ED50 = 3.5 mg/kg i.v. and 89 mg/kg p.o., respectively. OT-R antagonist 1 significantly inhibits spontaneous uterine contractions in pregnant rats near term when administered intravenously or orally. [1]
Nomifensine is a norepinephrine-dopamine reuptake inhibitor, increases the amount of synaptic norepinephrine and dopamine available to receptors by blocking the dopamine and norepinephrine reuptake transporters.
LY288513, a selective non-peptide CCK-B receptor antagonist with an IC50 value of 16 nM. LY288513 possesses both anxiolytic and antipsychotic potential[1][2][3].