Umbellulone is an active constituent of the leaves of Umbellularia californica. Umbellulone stimulates the TRPA1 channel in a subset of peptidergic, nociceptive neurons, activating the trigeminovascular system via this mechanism[1].
Desvenlafaxine-d10 is deuterium labeled Desvenlafaxine. Desvenlafaxine, the succinate salt form of the isolated major active metabolite of Venlafaxine (HY-B0196), is an orally active and BBB penetrated 5-HT and norepinephrine reuptake inhibitor, with IC50 values of 47.3 nM and 531.3 nM for hSERT and hNET, respectively. Desvenlafaxine shows weak binding affinity (62% inhibition at 100 μM) at the human dopamine (DA) transporter[1][2].
6,2',4'-Trimethoxyflavone is a potent aryl hydrocarbon receptor (AHR) antagonist. 6,2',4'-Trimethoxyflavone represses AHR-mediated gene induction[1].
BRL-15572 2Hcl is a 5-HT1D receptor antagonist with pKi of 7.9, also shows a considerable affinity at 5-HT1A and 5-HT2B receptors, exhibiting 60-fold selectivity over 5-HT1B receptor. IC50 Value: 7.9(pKi)Target: 5-HT1D Receptorin vitro: BRL-15572 displays high affinity and selectivity for h5-HT1D receptors. BRL-15572 has 60-fold higher affinity for h5-HT1D than 5-HT1B receptors. BRL-15572 binds to h5-HT1B and h5-HT1D receptors with pKB of less than 6 and 7.1, respectively. BRL-15572 stimulates [35S]GTP γ S binding in both cell lines, with potencies that correlated with their receptor binding affinities in both h5-HT1B and h5-HT1D receptor expressing cell lines. BRL-15572 reveals receptor binding affinities for 5-HT1A, 5-HT1B, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6 and 5-HT7 with pKi of 7.7, 6.1, 5.2, 6.0, 6.6, 7.4, 6.2, 5.9 and 6.3, respectively. In the h5-HT1D cell line, both BRL-15572 (1 μM) shifts the 5-HT concentration response curve with pKB of 7.1, respectively. BRL-15572 does have moderately high affinity at human 5-HT1A and 5-HT2B receptors.in vivo: In diabetic pithed rats, administration of the selective 5-HT1D receptor antagonist BRL-15572 (2 mg/kg) does not modify the decreased HR induced by vagal electrical stimulation. The effects of L-694,247 (50 μg/kg), a selective agonist for non-rodent 5-HT1B and 5-HT1D receptors, on the vagally induced bradycardia are not apparent after pretreatment with BRL-15572.
Dibucaine Hydrochloride is a local anesthetic of the amide type now generally used for surface anesthesia.Target: Sodium ChannelDibucaine is an amide local anesthetic. Dibucaine reduced the degradation of BSA-gold complex in the reservosomes, which was not caused either by an inhibition of the whole proteolytic activity of the parasite or by a reduction on the expression levels of cruzipain [1].Dibucaine, a quaternary ammonium compound, inhibited SChE to a minimum within 2 min in a reversible manner. The inhibition was very potent. It had an IC(50) of 5.3 microM with BuTch or 3.8 microM with AcTch. The inhibition was competitive with respect to BuTch with a K(i) of 1.3 microM and a linear-mixed type (competitive/noncompetitive) with respect to AcTch with inhibition constants, K(i) and K(I) of 0.66 and 2.5 microM, respectively. Dibucaine possesses a butoxy side chain that is similar to the butryl group of BuTch and longer by an ethylene group from AcTch [2].
Anisotropine methobromide is an orally active anticholinergic muscarinic antagonist. Anisotropine methobromide can inhibit gastric acid secretion and is used as an adjunct to peptic ulcers[1].
Lithium chloride hydrate, an orally active mood stabilizer, is a potent virus inhibitor and effective immunomodulatory agent. Lithium chloride hydrate has antidepressant activity by inhibiting GSK3β and promoting neurogenesis. Lithium chloride hydrate alleviates cognition dysfunction and the symptoms of acute mania and depression. Lithium chloride hydrate can also be used for research of virus infection and Alzheimer's disease[1][2][3].
ABT-639 hydrochloride is a novel, peripherally acting, selective T-type Ca2+ channel blocker.
TC-I 2014 (compound 5) is a potent Benzimidazole-containing transient receptor potential melastatin 8 (TRPM8) antagonist, with IC50 values of 0.8 nM, 3.0 nM and 4.4 nM for canine, human and rat channels respectively. TC-I 2014 exhibits antiallodynic properties in pain models[1].
Crebinostat is a potent histone deacetylase (HDAC) inhibitor with IC50 values of 0.7 nM, 1.0 nM, 2.0 nM and 9.3 nM for HDAC1, HDAC2, HDAC3 and HDAC6, respectively. Crebinostat potently induces acetylation of both histone H3 and histone H4 as well as enhances the expression of the cAMP response element-binding protein (CREB) target gene Egr1. Crebinostat increases the density of synapsin-1 punctae along dendrites in cultured neurons. Crebinostat can modulate chromatin-mediated neuroplasticity and exhibits enhanced memory in mice[1].
Aripiprazole (OPC-14597) monohydrate, an atypical antipsychotic, is a potent and high-affinity dopamine D2 receptor partial agonist. Aripiprazole monohydrate is an inverse agonist at 5-HT2B and 5-HT2A receptors and displays partial agonist actions at 5-HT1A, 5-HT2C, D3, and D4 receptors. Aripiprazole monohydrate can be used for the research of schizophrenia and COVID19[1][2][3][4].
LM22A-4 is a specific agonist of tyrosine kinase receptor B, used for neurological disease research.
TIPP is a potent and selective δ-opioid antagonist with a Ki value of 1.22 nM[1].
KV2 channel inhibitor-1 is a selective KV2 channel inhibitor with IC50s of 0.2 μM and 0.41 μM for KV2.1 and KV2.2, respectively. KV2 channel inhibitor-1 possesses good selectivity over KV1.2 (IC50>10 μM). KV2 channel inhibitor-1 is >10-fold selective over NaV channels and other KV channels and displays weak activity on CaV channels[1].
GNE-9278 is a highly selective positive allosteric modulator of NMDAR that acts at the GluN1 transmembrane domain (TMD). GNE-9278 acts on activated NMDARs to increase peak current and agonist affinity[1].
UBP710 is a selective NMDA receptor modulator. UBP710 displays greater activity in potentiating GluN2B-containing receptors than those containing GluN2A[1].
SB408124 Hcl is a non-peptide antagonist for OX1 receptor with Ki of 57 nM and 27 nM in both whole cell and membrane, respectively; exhibits 50-fold selectivity over OX2 receptor.IC50 Value: 57 nM(Ki)Target: OX1 Receptorin vitro: SB-408124 binds hypocretin type 1 receptor (HcrtR1) with pKi values of 7.57. Calcium mobilization studies shows that SB-408124 is a functional antagonist of the OX1 receptor with a affinity of approximately 50-fold selectivity over the OX2 receptor. A recent study indicates that pretreatment of primary cultures of rat astrocytes with SB-401824 before Orexin A administration significantly reduced the stimulatory action of Orexin A on both basal and forskolin-acivated cAMP production.in vivo: SB-408124 (30 μg/10 μL, administered intracerebroventricularly) decreases Orexin-A induced water intake in Wistar rats. Intracerebroventricularly administered Orexin-A (30 μg/10 μL) blocks the vasopressin (VP) level increase induced by either histamine or 2.5% NaCl administration, and this blocking effect is moderated by pretreatment with SB-408124. Intracerebroventricular pretreatment with SB-408124 (50 mM, 5 μL/h) prevents Bicuculline (BIC)-induced increases in endogenous glucose production (EGP).
Bilobalide is a biologically active terpenic trilactone present in Ginkgo biloba. An increasing number of studies have demonstrated its neuroprotective effects.IC50 Value: 3.33 (pIC50 Value) [1]Target: neuroprotectivein vitro: Inhibition by BB and GB was abolished in mutant receptors containing T6'S and S12'A substitutions, but their potencies were enhanced (42- and 125-fold, respectively) in S2'A mutant receptors [1]. BB enhanced the secretion of α-secretase-cleaved soluble amyloid precursor protein (sAPPα, a by-product of non-amyloidogenic processing of APP) and decreased the β amyloid protein (Aβ, a by-product of amyloidogenic processing of APP) via PI3K-dependent pathway [2].in vivo: Oral administration of bilobalide (10-30 mg/kg) significantly inhibited thermal hyperalgesia in response to carrageenan, capsaicin and paw incision, independent of dose, with an efficacy similar to that of diclofenac. In the carrageenan model, mechanical hypersensitivity and paw oedema were also significantly reduced after treatment with bilobalide (10-30 mg/kg) [3]. BB(4 and 8 mg/kg) significantly protected VD rats against cognitive deficits in the Morris water maze. Biochemical assessment showed that BB (4 and 8 mg/kg) increased superoxide dismutase (SOD) activity and glutathione (GSH) content, and decreased nitric oxide synthase (NOS) activity and malondialdehyde (MDA) content [4].Clinical trial: N/A
SSR504734 is an orally active, selective and reversible inhibitor of human, rat, and mouse GlyT1 (IC50=18, 15, and 38 nM, respectively). SSR504734 shows anti-schizophrenia, anti-anxiety and anti-depression activities[1].
Vigabatrin(γ-Vinyl-GABA; Sabril) is a structural analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) that irreversibly inhibits the catabolism of GABA by GABA transaminase.IC50 value:Target: GABA transaminaseClinical studies have shown that vigabatrin is superior to placebo in decreasing the frequency of infantile spasms. In tuberous sclerosis, vigabatrin may be considered the first-line treatment for IS. The mode of action is increasing concentrations of the inhibitory neurotransmitter GABA in the brain.A significant increase in seizure threshold was observed following systemic (i.p.) administration of high (600 or 1200 mg/kg) doses of vigabatrin. Bilateral microinjection of vigabatrin (10 μg) into either the anterior or posterior SNr also increased seizure threshold, but less markedly than systemic treatment.
11-Oxo etiocholanolone (11-Ketoetiocholanolone) is a metabolite of Etiocholanolone. Etiocholanolone is the excreted metabolite of testosterone and has anticonvulsant activity[1][2].
Pizotifen malate is a potent 5-HT2 receptor antagonist, with a high affinity for 5-HT1C binding site.
β-Amyloid (35-25) is areverse version of β-Amyloid (25-35) (HY-P0128).
BN201 promotes neuronal differentiation, the differentiation of precursor cells to mature oligodendrocytes (EC50 of 6.3 μM) in vitro, and the myelination of new axons (EC50 of 16.6 μM). BN201 is able to cross the blood-brain barrier by active transport and activate pathways (IGF-1 pathway) associated with the response to stress and neuron survival. BN201 has potently neuroprotective effects[1].
Modaline Sulfate is a MAO inhibitor, used in the treatment of depression.
NEO 376 is a selective modulator of 5-HT1 receptor, GABA receptor and dopamine receptor, with anti-psychotic actively.
Myomodulin is a neuropeptide present in molluscs, insects, and gastropods.
6‴-Feruloylspinosin is a flavonoid isolated from seeds of Ziziphus jujuba. 6‴-Feruloylspinosin can across the blood-brain barrier and enhance the expression of GABAAα1, GABAAα5, and GABABR1 mRNA in rat hippocampal neurons[1].
BChE-IN-8 (compound 20) is an orally active, potent and BBB-penetrated BChE (butyrylcholinesterase) inhibitor, with IC50 values of 0.15 nM (eqBChE, equine serum BChE) and 45.2 nM (hBChE), respectively. High stability of BChE-IN-8 contributes to significantly improved blood concentration and tissue exposure. BChE-IN-8 can exert neuro-protecting and cognition improving properties through multiple modulations, including cholinergic system, Aβ aggregation, neuropeptide levels. BChE-IN-8 can be used for Alzheimer's disease (AD) research[1].
DCB (3,3′-dichlorobenzaldazine) is an neutral allosteric modulator of themetabotropic glutamate receptor metabotropic glutamate receptor subtype 5 (mGluR5) . DCB blocks the positive allosteric regulation of mGluRs (mGluR5) with the help of 3,3′-difluorobenzaldazine (DFB). DCB shows the negative modulatory effect of 3,3′-dimethoxybenzaldazine (DMeOB)[1].