VU0155094 is a potent, selective pan-Group III mGlu positive allosteric modulator with IC50 of 3.43/1.5/0.93 uM for mGlu8/7/4, respectively; displays >30-fold selectivity over groups I and II mGlus (mGlu1/2/3/5/6).
L-Alpha glycerylphosphorylcholine (alpha-GPC, choline alfoscerate) is a natural choline compound found in the brain and in milk. It is also a parasympathomimetic acetylcholine precursor which may have potential for the treatment of Alzheimer's disease and dementia.IC50 value:Target: Anti-ADAlpha-GPC rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of the acetylcholine neurotransmitter. It is a non-prescription drug in most countries due to its Generally Recognised As Safe (GRAS) status [1]. Studies have investigated its efficacy for cognitive disorders including stroke and Alzheimer’s disease. An Italian multicentre clinical trial on 2,044 patients suffering from recent stroke were supplied alpha-GPC in doses of 1,000 mg/day for 28 days and 400 mg three times per day for the five ensuing months. The trial confirmed the therapeutic role of alpha-GPC on the cognitive recovery of patients based on four measurement scales, three of which reached statistical significance [2].
Oxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties.Target: mAChROxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination (urge incontinence), by decreasing muscle spasms of the bladder. Oxybutynin competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor. It also has direct spasmolytic effects on bladder smooth muscle as a calcium antagonist and local anesthetic, but at concentrations far above those used clinically. Oxybutynin is available orally in generic formulation or as the brand-names Ditropan, Lyrinel XL, or Ditrospam, as a transdermal patch under the brand name Oxytrol, and as a topical gel under the brand name Gelnique. Oxybutynin is also a possible treatment of hyperhidrosis (hyper-active sweating) [1-3].
Hexasodium phytate (Phytic acid hexasodium) is a phosphorus storage compound of seeds and cereal grains. Hexasodium phytate has a strong ability to chelate multivalent metal ions, specially zinc, calcium, iron and as with protein residue. Hexasodium phytate inhibits the enzymatic superoxide source xanthine oxidase (XO), and has antioxidative, neuroprotective, anti-inflammatory effects.
(Gly22)-amyloid beta-protein(1-40) (Arctic variant Ab40ARC (E22G)) is a peptide. (Gly22)-amyloid beta-protein(1-40) can be used for the research of Alzheimer's disease[1].
Glucagon (19-29), human is a potent and efficient inhibitor of insulin secretion.
AM1241 is a potent, typical[2] and selective CB2 receptor agonist, with a Ki of 3.4 nM in a mouse spleen, and the Ki for CB1 receptor in rat brain is 280 nM, 82-fold selectivity for the CB2 receptor in rodent tissue[1]. AM1241 relieves migraine, stroke, and neuropathic pain，also has a potent effect on Parkinson's disease[2]. AM1241 prevents oxidative damage and activates STAT3 through the phosphorylation of Akt and Erk1/2[3].
Almorexant Hcl (ACT078573) is a potent and competitive dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM for OX1 and OX2, respectively.
Cirsiliol is a potent and selective 5-lipoxygenase inhibitor and a competitive low affinity benzodiazepine receptor ligand.
GOAT-IN-1 is an inhibitor of ghrelin O-acyltransferase (GOAT), which could be useful for the prophylaxis or treatment of obesity, diabetes, hyperlipidemia, metabolic, non-alcoholic fatty liver, steatohepatitis, sarcopenia, appetite control, alcohol/narcotic dependence, Alzheimer’s disease, Parkinson’s disease, cerebrovascular dementia, cerebral apoplexy, cerebral infarction, cardic disease, some kind of tumors.
Epiboxidine hydrochloride is a potent and selective neural nAChR agonist with Kis of 0.46 nM and 1.2 nM for rat and human α4β2 nAChRs, respectively. Epiboxidine hydrochloride is a methylisoxazole analog of the alkaloid Epibatidine, and is also an analog of another nAChR agonist, ABT 418[1].
Antioxidant agent-2 (comp 3c), an BBB-penetrated antioxidant agent and a selective metal ions chelator, presents good neuroprotective effect and hepatoprotective effect for the study of Alzheimer’s disease[1].
SPD-473 citrate is a serotonin/dopamine/norepinephrine reuptake inhibitior.
Brexpiprazole (OPC-34712) hydrochloride, an atypical orally active antipsychotic drug, is a partial agonist of human 5-HT1A and dopamine D2L receptor with Kis of 0.12 nM and 0.3 nM, respectively. Brexpiprazole hydrochloride is also a 5-HT2A receptor antagonist with a Ki of 0.47 nM. Brexpiprazole hydrochloride also shows potent antagonist activity at human noradrenergic α1B (Ki=0.17 nM) and α2C receptors (Ki=0.59 nM)[1][2].
Ziprasidone (CP-88059) mesylate trihydrate is an orally active combined 5-HT and dopamine receptor antagonist[1]. Ziprasidone mesylate trihydrate has affinities for Rat D2 (Ki=4.8 nM), 5-HT2A (Ki=0.42 nM) and 5-HT1A (Ki=3.4 nM)[1].
κM-Conotoxin RIIIK is a potassium channel antagonist. κM-Conotoxin RIIIKcan block voltage-activated potassium ion channels [1].
Talnetant Hcl(SB 223412 Hcl) is a potent and selective NK3 receptor antagonist(ki=1.4 nM, hNK-3-CHO); 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 uM.IC50 Value: 1.4 nM (hNK-3-CHO binding Ki) [1]Target: NK3 receptorin vitro: In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits) [1]. Talnetant has high affinity for recombinant human NK3 receptors (pKi 8.7) and demonstrates selectivity over other neurokinin receptors (pKi NK2 = 6.6 and NK1<4). In native tissue-binding studies, talnetant displayed high affinity for the guinea pig NK3 receptor (pKi 8.5) [3].in vivo: Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days [2]. Talnetant (3-30 mg/kg i.p.) significantly attenuated senktide-induced 'wet dog shake' behaviors in the guinea pig in a dose-dependent manner. Microdialysis studies demonstrated that acute administration of talnetant (30 mg/kg i.p.) produced significant increases in extracellular dopamine and norepinephrine in the medial prefrontal cortex and attenuated haloperidol-induced increases in nucleus accumbens dopamine levels in the freely moving guinea pigs [3].Toxicity: Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo [2].Clinical trial: Study Of Talnetant Versus Placebo And Risperidone In Schizophrenia. Phase 2
ABC44 is a potent serine hydrolase inhibitor with IC50s of 0.1 μM and 6.5 μM for palmitoyl protein thioesterase 1 (PPT1) in situ and in vitro, respectively. ABC44 can be used for researching infantile neuronal ceroid lipofuscinosis[1].
THK-523 has demonstrated its high affinity and selectivity for tau pathology both in vitro and in vivo. 18F-THK523 is a potent tau imaging radiotracer. 18F-THK523 is a potent in vivo tau imaging ligand for Alzheimer's disease[1].
JNJ10191584 (VUF6002) is an orally active and selective histamine H4 receptor antagonist with a Ki value of 26 nM. JNJ10191584 shows 540-fold selectivity to H4 receptor over H3 receptor with a Ki value of 14.1 μM. JNJ10191584 inhibits chemotaxis of eosinophils and mast cells with IC50 values of 530 nM and 138 nM, respectively[1][2].
Miroestrol is a highly active phytoestrogen. Miroestrol can produce mammogenic effect. Miroestrol exhibits bone loss prevention and neuroprotective in ovariectomized mice. Miroestrol also can reduce cancer risk[1][2][3][4].
SNX-482, a peptidyl toxin of the spider Hysterocrates gigas, is a potent, high affinity, selective and voltage-dependent R-type CaV2.3 channel blocker with an IC50 of 30 nM. SNX-482 has antinociceptive effect[1][2][3].
Mirtazapine D3 (Org3770 D3; 6-Azamianserin D3) is a deuterium labeled Mirtazapine. Mirtazapine is a 5-HT receptor inhibitor. Mirtazapine is a potent and orally active noradrenergic and specific serotonergic antidepressant (NaSSA) agent by blocking 5-HT2 and 5-HT3 receptors[1].
A small molecule autophagy enhancer that specificly inhibits myotubularin-related phosphatase MTMR14; at concentrations of 2, 10, and 100 uM, AUTEN-67 inhibits MTMR14 by nearly 3%, 25%, and 70%, respectively; shows no activity for CDC25B , other phosphatase, PTPN1; significantly increases autophagic flux in cell lines and in vivo models, promotes longevity and protects neurons from undergoing stress-induced cell death; also restores nesting behavior in a murine model of Alzheimer disease, without apparent side effects.
Methylergometrine maleate (Methylergonovine maleate) is an ergot alkaloid and an active metabolite of Methysergide with vasoconstrictive and uterotonic activity. Methylergometrine maleate is a potent, selective and orally active 5-HT receptors antagonist with a pA2 value of 9.6. Methylergometrine maleate has antimigraine and dopaminergic activity. Methylergometrine maleate can used for the prevention and control of postpartum hemorrhage[1][2][3].
Furobufen, an anti-inflammatory agent, produces antiarthritic, antipyretic effects. Furobufen has an analgesic effect in inflamed tissue[1].
Dehydroaripiprazole (OPC-14857) is an active metabolite of Aripiprazole. Aripiprazole is an antipsychotic agent and is metabolized by CYP3A4 and CYP2D6 forming mainly Dehydroaripiprazole. Dehydroaripiprazole has with antipsychotic activity equivalent to Aripiprazole[1][2][3].
MARK-IN-1 is a potent microtubule affinity regulating kinase (MARK) inhibitor with an IC50 of <0.25 nM.
U-54494A is a benzamide derivative related to κ-opioid receptor agonists, U-54494A has an anticonvulsant activity[1].
GSK1059865 is a potent orexin 1 receptor antagonist.