Delsoline, a major alkaloid of Delphinium anthriscifolium Hance, has both a curare-like effect and a ganglion-blocking effect and is used to relieve muscle tension or hyperkinesia. D. anthriscifolium Hance has effects of dispelling wind and dampness, activating collaterals, and relieving pains and is used to treat rheumatism, hemiplegia, indigestion, and cough[1].
CTB (Cholera Toxin B subunit) is a potent p300 histone acetyltransferase activator[1]. CTB can effectively induce apoptosis in MCF-7 cells[2].
Orexin receptor antagonist 4 is potent and selective orexin 2 receptor (OX2R) antagonist with an IC50 of 4.27 nM. Orexin receptor antagonist 4 is 61-fold selective for the OX2R over the OX1R (IC50 of 295 nM) (WO2018206959A1; example 1)[1].
GW1929 hydrochloride is an orally active peroxisome proliferator-activated receptor-γ (PPARγ) agonist with a pKi of 8.84 for human PPAR-γ, and pEC50s of 8.56 and 8.27 for human PPAR-γ and murine PPAR-γ, respectively. GW1929 hydrochloride has antidiabetic efficacy and neuroprotective potential. GW1929 hydrochloride suppresses neuronal apoptosis and shows anti-inflammatory potential[1][2][3].
NPEC-caged-LY379268 is a type II mGluR agonist[1].
Spiclomazine hydrochloride (APY-606) is an antipsychotic and antitumor agent. Spiclomazine hydrochloride inhibits KRas. Spiclomazine hydrochloride induces cancer cell apoptosis[1][2].
mGAT3/4-IN-1 (compound 19b) is a potent mGAT3/mGAT4 inhibitor, with pIC50 values of 5.31 and 5.24, respectively. mGAT3/4-IN-1 exhibits a significant tactile allodynia reduction in diabetic neuropathic mice[1].
CY 208-243 is a selective dopamine D1 receptor agonist which exhibits antiparkinsonian activity[1].
Evifacotrep, a short transient receptor potential channel 5 (TRPC5) antagonist (WO2020061162, compound 100), can be used for the research of neurological diseases[1].
Tamsulosin-d4 (hydrochloride) is deuterium labeled Tamsulosin (hydrochloride). Tamsulosin hydrochloride ((R)-(-)-YM12617) is an inhibitor of α1-adrenergic receptor. Tamsulosin hydrochloride is used for the research of prostatic hyperplasia. Tamsulosin hydrochloride attenuates abdominal aortic aneurysm growth in animal models[1].
Metixene (Piperidine) is an anticholinergic and antiparkinsonian agent. Metixene potently inhibits binding of quinuclidinyl benzilate (QNB) with the muscarinic receptor, IC50 and Ki values of 55 nM and 15 nM, respectively. Metixene can be used for the research of parkinsonian[1][2][3].
Royal Jelly acid (Queen Bee Acid) is a fatty acid constituent of royal jelly, promotes the growth and protection of neurons, reduces anxiety-like phenotypes[1].
Aprophen (Aprofene) is an antimuscarinic inhibitor. Aprophen can be used for the research of central nervous system[1].
BMS-986163 is a negative allosteric modulator of GluN2B. The prodrug BMS-986163 rapidly converts to its active parent molecule BMS-986169 (Ki=4 nM, IC50=24 nM).
Zonisamide is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug.Target: Calcium channel inhibitor; Sodium channel inhibitorZonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure. Zonisamide is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug. It has shown activity in various animal models of epilepsy, and although a detailed mode of action awaits clarification it appears to block the propagation/spread of seizure discharges and to suppress the epileptogenic focus [1].Zonisamide 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (-51% versus -16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100-500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35-42%) compared with placebo following zonisamide 400-600 mg/day, enabling 20-27% of patients to attain >or=75% reduction in seizure frequency [2].Clinical indications: Epilepsy; Lewy body dementia; Parkinsons diseaseToxicity: Anorexia; Somnolence; Dizziness; Irritability; Confusional state; Depression; Diplopia; Memory impairment
FAUC 365 is a highly dopamine D3 receptor-selective antagonist with Ki values of 0.5 nM, 340, 2600, and 3600 nM at D3, D4.4, D2short, and D2Long receptors, respectively. FAUC 365 can be used for the research of schizophrenia, and Parkinson's disease[1][2].
S1R agonist 1 (Compound 6b) hydrochloride is a selective S1R agonist with Kis of 0.93 nM and 72 nM for S1R and S2R, respectively. S1R agonist 1 hydrochloride exhibits neuroprotection against ROS and NMDA-induced neurotoxicity[1].
Zilganersen sodium is a glial fibrillary acidic protein (GFAP) inhibitor. Zilganersen sodium can be used in Alexander disease (AxD) research[1][2].
Procaine Hydrochloride is a local anesthetic drug of the amino ester group.Target: OthersProcaine is a local anesthetic of the ester type that has a slow onset and a short duration of action.Procaine (0.01-100 microM) inhibited the 5-HT3 receptor-mediated inward current in the whole-cell patch clamp recording. Procaine appears to produce a competitive inhibition on 5-HT3 receptors with a KD of 1.7 microM [1]. Procaine is a DNA-demethylating agent that produces a 40% reduction in 5-methylcytosine DNA content as determined by high-performance capillary electrophoresis or total DNA enzyme digestion. Procaine can also demethylate densely hypermethylated CpG islands. Procaine also has growth-inhibitory effects in these cancer cells, causing mitotic arrest [2]. Procaine functions as an excitant of limbic system cells, and that procaine alters synaptic transmission in some, but not all, output pathways from the amygdale [3].
β-Lipotropin (61-69) is a potent opioid agonist[1][2].
Atipamezole hydrochloride is a synthetic α2-adrenoceptor antagonist with a Ki of 1.6 nM.
HG-10-102-01 is a potent and selective inhibitor of wild-type LRRK2(IC50=23.3 nM) and the G2019S mutant(IC50=3.2 nM)IC50 Value: 23.3 nM (WT LRRK2); 3.2 nM (LRRK2 G2019S) [1]Target: LRRK2HG-10-102-01 maintains the ability to potently inhibit the biochemical activity of wild-type and G2019S mutant LRRK2. HG-10-102-01 exhibited biochemical IC50s of 20.3 and 3.2 nM against wild-type LRRK2 and LRRK2[G2019S], respectively. At a concentration of 10 μM, HG-10-102-01 only inhibited the kinase activities of MLK1 and MNK2 to greater than 80% of the DMSO control. Dose-response analysis revealed inhibition of MLK1 with an IC50 2.1 μM and MNK2 with an IC50 0.6 μM. KinomeScan analysis against a near comprehensive panel of 451 kinases at a concentration of 1 μM resulted in no interactions detected with kinases other than G2019S LRRK2 with the exception of one mutant form of c-Kit (L576P) demonstrating the outstanding selectivity of this inhibitor.HG-10-102-01 significantly inhibited phosphorylation of wildtype LRRK2 and LRRK2[G2019S] mutant at Ser910 and Ser935 at 0.3-1.0 μM in cell culture, which is approximately the same potency as LRRK2-IN-1 (1). HG-10-102-01 is relatively insensitive to the A2016T mutation which suggests that this mutant will not be useful to validate whether the pharmacological effects of the compound are LRRK2-dependent.HG-10-102-01 can inhibit phosphorylation of Ser910 and Ser935 of LRRK2 in brain and peripheral tissues following intraperitoneal doses of 50 mg/kg. Further optimization of this chemo-type especially in regards to in vivo half-life will be reported in due course [1].
Ulefnersen is a RNA-binding protein fused-in sarcoma (FUS) synthesis reducer[1]. Ulefnersen can be used in Amyotrophic Lateral Sclerosis (ALS) research[2].
Apronal (Allylisopropylacetylurea, Apronalide) is a hypnotic and sedative drug that has been withdrawn in several countries due to side effects.
Pramocaine hydrochloride is a topical anesthetic, and used as an antipruritic.
MW-150 dihydrochloride dihydrate (MW01-18-150SRM dihydrochloride dihydrate) is a selective inhibitor of p38αMAPK isoform with a ki of 101 nM[1].
Exendin (5-39) is a potent glucagon-like peptide 1 (GLP-1) receptor antagonist. Exendin (5-39) improves memory impairment in β-amyloid protein-treated rats[1].
γ-Acetylenic GABA hydrochloride is a GABA transaminase inhibitor.
Dihydromunduletone is a rotenoid derivative that selectively inhibits GPR56 (IC50=21 uM) and GPR114/ADGRG5, but not GPR110 or Class A GPCRs; maximally inhibits GPR56 at 50 uM, also dramatically inhibits GPR114 7TM–stimulated Gs activity; also inhibit the growth of the zebrafish intersegmental vessels.
SSR 146977 is a potent and selective antagonist of the tachykinin NK3 receptor. SSR 146977 inhibits the binding of radioactive neurokinin B to NK3 receptors in Chinese hamster ovary cells, with a Ki of 0.26 nM[1].