Neurological Disease

Zederone is a sesquiterpene. Zederone inhibits ovarian cancer cell proliferation through mTOR/p70s6K signalling pathway. Zederone inhibits CYP activities with IC₅₀s of 2.9 μM (CYP2B6), 9.2 μM (CYP2C9), 11,2 μM (CYP2C19) and >30 μM (CYP1A2 and CYP2D6). Zederone is hepatotoxic with LD₅₀ value at 24 hours in mice of approximately 223 mg/kg and cytotoxic against the KG1a cell line. Zederone shows antibacterial activity against a number of multi-drug resistant and Methicillin (HY-121544)-resistant Staphylococcus aureus strain. Zederone shows cognition improving capacity and assists in the modulation of gut bacterial dysbiosis.

Pregnenolone acetate (compound #43), a nonmetabolized Pregnenolone (HY-B0151) analog, can promote neurite extension and induce a change in growth cone morphology in primary cultures of cerebellar granule neurons. Pregnenolone acetate, a neurosteroid, increases microtubule polymerization. Pregnenolone acetate has the potential for neurodevelopmental diseases research.

Tiapride hydrochloride is a selective and orally active D₂ and D₃ dopamine receptors antagonist with IC₅₀ values of 110-320 nM and 180 nM, respectively. Tiapride hydrochloride shows anti-dyskinetic activity and anxiolytic activity. Tiapride hydrochloride is a neuroleptic agent.

Rubiadin is an orally active free radical scavenger that inhibits the activation of the NF-κB pathway. Rubiadin inhibits osteoclast formation, bone resorption, lipid peroxidation, HBV DNA replication and cancer cell proliferation; reduces pro-inflammatory cytokine levels; induces cancer cell apoptosis; and possesses antifungal, antimalarial, antibacterial and anticonvulsant activities. Rubiadin can be used in the research of osteoporosis, acute inflammation, chronic inflammation, carbon tetrachloride-induced liver injury, Alzheimer's disease, breast cancer, iron overload disorders, hepatitis B virus infection, colon cancer, liver cancer, T-lymphocytic leukemia, cervical cancer, diabetic nephropathy, epileptic seizures, fungal infections, malaria and bacterial infections.

SB-216641A (SB-216641 hydrochloride) is a selective antagonist of 5-HT_1B/D receptor. SB-216641A shows high affinity and selectivity for h5-HT_1B receptors over h5-HT_1D receptors. SB-216641A inhibits the function of SKF-99101H.

Decanoic acid-d₅ is the deuterium labeled Decanoic acid. Decanoic acid, a component of medium chain triclycerides, is a brain-penetrant and non-competitive inhibitor of AMPA receptor. Decanoic acid has antiseizure effects.

Nepafenac (AHR 9434; AL 6515), a nonsteroidal anti-inflammatory agent, is a topically administered COX-2 inhibitor with an IC₅₀ of 0.12 μM. Nepafenac exhibits only weak COX-1 inhibitory activity (IC₅₀ = 64.3 μM). Nepafenac possesses unique prodrug properties, which enable it to rapidly convert into the active metabolite Amfenac (HY-17479) in the ocular tissues, thereby achieving high concentrations in the retina and choroid. Nepafenac reduces inflammation and pain by inhibiting the activity of cyclooxygenase (COX) enzymes and thereby decreasing the production of prostaglandin PGE_₂. Nepafenac can delay the metastasis of uveal melanoma (UM) in rabbit eyes. Nepafenac is mainly used for pain management and inflammation control after ophthalmic surgeries.

CPCCOEt is a low affinity, selective, non-competitive and reversible antagonist of metabotropic glutamate receptor 1b (mGluR1b).

NCGC 607 is a noninhibitory small-molecule chaperone of glucocerebrosidase (GCase). NCGC 607 can increase GCase activity, reduce α-synuclein levels, and decrease glycolipid levels. NCGC 607 can be used in the research of Gaucher disease and Parkinson's disease.

Roxindole hydrochloride (EMD 38362), an indot-alkyl-pipenidine, is a potent agonist at dopamine autoreceptors, with an affinity for the D2-like subtype in the low nanomolar range. Roxindole can be used for the research of positive and negative schizophrenic symptoms. Roxindole is a 5-HT_1A agonist and 5-HT uptake inhibitor with high affinity for 5-HT_1A (IC₅₀=0.9 nM). Antipsychotic and antidepressant activities.

NB-3 is a nicotinamide adenine dinucleotide (NAD) hydrolase SARM1 inhibitor. NB-3 intercepts NAD hydrolysis and undergoes covalent conjugation with the reaction product adenosine diphosphate ribose (ADPR). The resulting small-molecule ADPR adducts are highly potent and confer compelling neuroprotection in neurological injury.

(-)-Syringaresinol is an orally active isomer of syringaresinol (HY-N8307) found in Annona Montana. (-)-Syringaresinol exhibits antioxidant, anti-inflammatory, and anticancer activities. (-)-Syringaresinol can alleviate ulcerative colitis via the PI3K-Akt/MAPK/Wnt signaling pathway. (-)-Syringaresinol inhibits HL-60 cell proliferation by arresting the G1 phase and inducing apoptosis. (-)-Syringaresinol inhibits LPS (HY-D1056)-induced microglial activation by downregulating the NF-κB p65 signaling pathway and its interaction with ERβ, exerting anti-neuroinflammatory effects.

[Sar9,Met(O2)11]-Substance P is a tachykinin NK₁ receptor selective agonist.

Cannflavin B is a flavonoid compound that can be isolated from Cannabis sativa L. Cannflavin B is inhibitors of PGE₂ release (IC₅₀: 0.7 μM), mPGES-1 (IC₅₀: 3.7 μM), and 5-lipoxygenase. Cannflavin B has multiple activities such as anti-inflammatory, antioxidant, anti-glycation, anti-ferroptosis, anti-tumor, and anti-Leishmania (IC₅₀: 14 μM). Cannflavin B can also inhibit the TrkB-BDNF signaling pathway.

Spinacine ((S)-Spinacine) is a GABA uptake inhibitor. Spinacine enhances synaptic GABA effects via inhibition of gamma-aminobutyric acid uptake in cerebral cortex slices. Spinacine inhibits reflex responses of ventral roots in isolated spinal cord. Spinacine inhibits motor activity and reduces approaches to water dispensers in conflict situations. Spinacine raises pain sensitivity threshold via subarachnoidal injection.

Tetrahydropalmatine (DL-Tetrahydropalmatine) hydrochloride possesses analgesic effects. Tetrahydropalmatine hydrochloride acts through inhibition of amygdaloid release of dopamine to inhibit an epileptic attack in rats.

Noscapine ((S,R)-Noscapine) hydrochloride is an orally active phthalideisoquinoline alkaloid with potent antitussive. Noscapine hydrochloride exerts its antitussive effects by activating sigma opioid receptors and is a non-competitive Bradykinin inhibitor. Noscapine hydrochloride disrupts microtubule dynamics, induces mitotic arrest and apoptosis. Noscapine hydrochloride possesses anticancer, neuroprotective, anti-inflammatory activities, and can crosse the blood-brain barrier.

Obtusin, isolated from Cassia obtusifolia Linn seed, is a highly selective and competitive human monoamine oxidase-A (hMAO-A) inhibitor with an IC₅₀ of 11.12 μM and a K_i of 6.15 μM. Obtusin plays a preventive role in neurodegenerative diseases, especially anxiety and depression.

Atabecestat (JNJ-54861911) is a potent brain-penetrant and orally active β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor, achieves robust and high CSF Aβ reduction. Atabecestat s tolerated and displays a sustained pharmacokinetic (PK) and pharmacodynamic (PD) characteristics. Atabecestat has the potential for Alzheimer's Disease treatment.

Marein has the neuroprotective effect due to a reduction of damage to mitochondria function and activation of the AMPK signal pathway. Marein improves insulin resistance induced by high glucose in HepG2 cells through CaMKK/AMPK/GLUT1 to promote glucose uptake, through IRS/Akt/GSK-3β to increase glycogen synthesis, and through Akt/FoxO1 to decrease gluconeogenesis. Marein is a HDAC inhibitor with an IC₅₀ of 100 μM. Marein has beneficial antioxidative, antihypertensive, antihyperlipidemic and antidiabetic effects.