MK-2894 sodium salt is a highly potent and selective second generation EP4 antagonist.IC50 value:Target: EP4MK-2894 exhibits favorable pharmacokinetic profile in a number of preclinical species and potent anti-inflammatory activity in several animal models of pain/inflammation. MK-2894 also shows favorable GI tolerability profile in rats when compared to traditional NSAID indomethacin.
MK-3207 is a potent and orally bioavailable CGRP receptor antagonist (IC50= 0.12 nM; Ki value= 0.024 nM); highly selective versus human AM1, AM2, CTR, and AMY3.IC50 Value: 0.024 nM (Ki, Human CGRP) [1]In common with other CGRP receptor antagonists, MK-3207 displays lower affinity for human CGRP receptors from other species, including canine and rodent.in vitro: MK-3207 is a potent antagonist of the human and rhesus monkey CGRP receptors (K(i) = 0.024 nM). in vivo: MK-3207 produced a concentration-dependent inhibition of dermal vasodilation, with plasma concentrations of 0.8 and 7 nM required to block 50 and 90% of the blood flow increase, respectively. The tritiated analog [3H]MK-3207 was used to study the binding characteristics on the human CGRP receptor. [3H]MK-3207 displayed reversible and saturable binding (K(D) = 0.06 nM), and the off-rate was determined to be 0.012 min(-1), with a t(1/2) value of 59 min [1]. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5?mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100?mg) were continued into the second stage [2].Clinical trial: MK-3207 for the treatment of acute migraines. Phase 2b
Picraline is a natural alkaloid that targets opioid receptors with binding affinities with Ki values of 132 μM, 2.38 μM and 98.8 μM for μOR, κOR and δOR, respectively[1].
Donitriptan hydrochloride (F-11356) is a potent, high efficacy agonist at 5-HT1B/1D receptors with pKis of 9.4 and 9.3, respectively[1].
Beclometasone dipropionate is a potent glucocorticoid agonist; it is a prodrug of the free form, beclometasone. IC50 Value: 0.2 nM (Inhibiting thymidine incorporation) [1]Target: glucocorticoid receptorin vitro: Cortisol and beclomethasone dipropionate were more potent than salbutamol in inhibiting thymidine incorporation with IC50 values of 5 nM and 0.2 nM respectively. Cortisol 100 nM led to a 16.6 +/- 6.5% reduction and beclomethasone dipropionate 3 nM led to a 17.8 +/- 5.8% reduction in cell number [1]. in vivo: Controlled trials involving 497 adults and children demonstrated similar clinical efficacy between nebulized BDP and either nebulized fluticasone propionate or nebulized budesonide. Meta-analyses show that BDP, like other inhaled corticosteroids, has no major influence on patient height, urinary cortisol concentration, or bone metabolism [2]. Beclometasone dipropionate (BDP) 800 microgday(-1) suspension for nebulization and budesonide (BUD) 750 microg day(-1) given by nebulization in a twice-daily regimen, and when used in addition to the usual maintenance therapy, resulted in comparable clinical efficacy across all parameters [3]. Clinical trial: Efficacy and Tolerability of Beclometasone/Formoterol Single Inhaler in Patients With Moderate to Severe Persistent Asthma. Phase 3
Fesoterodine is an orally active, nonsubtype selective, competitive muscarinic receptor (mAChR) antagonist with pKi values of 8.0, 7.7, 7.4, 7.3, 7.5 for M1, M2, M3, M4, M5 receptors, respectively. Fesoterodine is used for the overactive bladder (OAB)[1][2].
Dolasetron(MDL-73147) is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy.
Norisoboldine hydrochloride is an orally active natural aryl hydrocarbon receptor (AhR) agonist. Norisoboldine hydrochloride, as a major isoquinoline alkaloid present in Radix Linderae, can be used for the research of Rheumatoid arthritis and Ulcerative colitis[1][2].
(R,R)-Palonosetron Hydrochloride is the active enantiomer of Palonosetron.
Prasugrel Maleic acid is a platelet inhibitor with IC50 value of 1.8 μM.Target: P2Y12 receptorPrasugrel Maleic acid is a novel platelet inhibitor used for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who are to be managed with PCI [2].Prasugrel Maleic acid reduces the aggregation ("clumping") of platelets by irreversibly binding to P2Y12 receptors. In rat platelets, prasugrel Maleic acid AM inhibited in vitro platelet aggregation induced by ADP (10 μm) with an IC50 value of 1.8 Μm [2]. Clinical indications: Acute coronary syndrome; Ischemic heart disease; Sickle cell anemia; Stroke; Vascular occlusive diseaseFDA Approved Date: February 2009Toxicity: Hypertension; Headache; Hypercholesterolemia/hyperlipidemia; Nausea; Epistaxis
Tetrahydromagnolol (Magnolignan), a main metabolite of Magnolol, is a potent and selective cannabinoid CB2 receptor agonist with an EC50 of 170 nM and a Ki of 416 nM. Tetrahydromagnolol possesses 20-fold more selective for CB2 receptor than CB1 receptor. Tetrahydromagnolol is also a weak GPR55 receptor antagonist[1].
V-0219 is a small molecule positive allosteric modulator (PAM) of GLP-1R with Emax of 60% in the cAMP assay.V-0219 potentiated insulin secretion in INS-1 β-cells with EC50 of 0.25 nM, the best response was observed at 0.1 nM, when a fixed concentration of 0.2 nM of GLP-1 was added to the dose-response curve of 9, the maximal response observed reached a plateau at 0.1 nM, with an EC50 value of 0.008 nM.V-0219 shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents.
KRAS inhibitor-20 is a small molecular inhibitor of KRasG12C, the oncogenic mutant. KRAS inhibitor-20 inhibits KRasG12C with the IC50 value <10 nM[1].
Nolpitantium (SR140333) is a potent, selective, competitive, non-peptide tachykinin NK1 receptor antagonist. Nolpitantium blocks the activation of rat thalamic neurons after nociceptive stimulation[1].
MCHR1 antagonist 3 is a potent the melanin-concentrating hormone receptor-1 (MCHR1) antagonist. MCHR1 antagonist 3 is used to regulate energy metabolism[1].
KSK94 is a high-affinity histamine H3 receptor antagonist, with Kis of 7.9, 2958, 75.2 nM for H3 receptor, sigma-1, sigma-2 receptor respectively. KSK94 can be used for research of nociceptive and neuropathic pain[1].
Drinabant (AVE1625) is an orally active CB1 receptor antagonist. Drinabant (AVE1625) inhibits the agonist-stimulated calcium signal with IC50 values of 25 nM and 10 nM for the hCB1-R and rCB1-R, respectively, and is ineffective for the hCB2-R[1].
σ1 Receptor/μ Opioid receptor modulator 1 (Compound 44) is a potent σ1 receptor antagonist and μ opioid receptor agonist with Kis of 1.86 nM and 2.1 nM, respectively.σ1 Receptor/μ Opioid receptor modulator 1 exhibits potent analgesic activity. σ1 Receptor/μ Opioid receptor modulator 1 can be used for the research of neuropathic pain[1].
JNJ-5207852 dihydrochloride is a selective and potent histamine H3 receptor (H3R) antagonist, with pKis of 8.9, 9.24 for rat and human H3R, respectively.
Odapipam (NNC 756) is a selective, high affinity and benzazepine dopamine D1 receptor antagonist with a Kd of 0.18 nM. Odapipam is also a superior positron emission tomography (PET) radiotracer[1][2].
CASIN is a selective GTPase Cdc42 inhibitor with IC50 of 2 uM. In vitro: Treatment with CASIN (5 uM) reduced the elevated level of active Cdc42 observed in aged primitive hematopoietic cells to the level observed in young cells In vivo: Reverses the aging-related and polarity phenotype of aged HSCs to that of young HSCs.
Quetiapine D4 fumarate is the deuterium labeled Quetiapine, which is an atypical antipsychotic.
Mosliciguat is a guanylate cyclase activator[1].
Cenicriviroc is a dual CCR2/CCR5 antagonist, also inhibits both HIV-1 and HIV-2, and displays potent anti-inflammatory and antiinfective activity.
AGN 192836 is a potent and selective α2 adrenergic agonist with EC50s of 8.7, 41 and 6.6 nM for α2A, α2B and α2C receptor, respectively.
Pindolol-d7 (LB-46-d7) is the deuterium labeled Pindolol. Pindolol (LB-46) is a nonselective β-blocker with partial beta-adrenergic receptor agonist activity, also functions as a 5-HT1A receptor weak partial antagonist (Ki=33 nM)[1][2].
Dihydrexidine hydrochloride (DAR-0100 hydrochloride) is a high potent, selective and full efficacy D1-like dopamine receptor (D1/D5) agonist, with an IC50 of 10 nM for D1 receptor. Dihydrexidine hydrochloride exhibits potent antiparkinsonian activity[1][2][3][4].
Dopamine D3 receptor ligand-4 (compound 6) is a potent and selective dopamine D3 receptor ligand, with a Ki of 0.5 nM. Dopamine D3 receptor ligand-4 shows high level of selectivity for D3 over D2 (Ki=7.43 nM). Dopamine D3 receptor ligand-4 can be used for the research of Cocaine use disorder[1].
F 14679 is a prototypical 5-HT1A agonist with a pKi of 10.23. F 14679 induces large Ca2+ responses[1].
Losartan-d9 is the deuterium labeled Losartan[1]. Losartan is an angiotensin II receptor antagonist, competing with the binding of angiotensin II to AT1 receptors with IC50 of 20 nM.