Neurological Disease

MDR-1339 (DWK-1339) is an orally active and blood-brain-barrier-permeable Aβ-aggregation inhibitor, used in the research of Alzheimer's disease.

Latrepirdine dihydrochloride is a neuroactive compound with antagonist activity at histaminergic, α-adrenergic, and serotonergic receptors. Latrepirdine stimulates amyloid precursor protein (APP) catabolism and amyloid-β (Aβ) secretion.

MT-110 (BPN-0027490) is a non-muscle myosin NMIIB-selective inhibitor with high brain penetration and favorable safety profile. MT-110 specifically disrupts NMIIB-dependent actin dynamics in dendritic spines, while it exerts no significant adverse effects on cardiac myosin II and cardiac functions (such as cardiac output and heart rate) at tested concentrations. A single administration of MT-110 produces long-lasting (sustained for several weeks) blockade of methamphetamine motivation associated with environmental cues. MT-110 exhibits extremely high specificity, with no interference with cocaine motivation, hippocampus-dependent memory, fear memory, or locomotor and anxiety-like behaviors. MT-110 serves as a valuable tool compound for investigating the mechanisms of methamphetamine use disorder.

Etedesiran is a component of the AOC drug Delpacibart etedesiran (HY-177565), formed by the reaction of an siRNA that induces cleavage of mRNA encoding myotonic dystrophy protein kinase (MTPK or DMPK) with SMCC linker (HY-42360). Etedesiran carries a maleimide group at its terminus, which can react with cysteine or lysine and is used for the synthesis of AOC drugs. Etedesiran is applicable to research related to myotonic dystrophy type 1.

PRX-08066 is a selective and orally active 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist with a K_i of 3.4 nM. PRX-08066 inhibits the MAPK pathway, 5-HT release and fibrotic factor (TGFβ1, CTGF and FGF2) expression. PRX-08066 inhibits the proliferation of KRJ-I cells and induces apoptosis (caspase-3 activation). PRX-08066 inhibits pulmonary vascular remodeling. PRX-08066 can be used of pulmonary Arterial Hypertension (PAH) and neuroendocrine tumor (NET).

WM-662 is a WDR5-MYC interaction inhibitor, with an IC₅₀ of 18 μM. WM-662 has potential for the research of cancer, aging, and neurodegenerative disorders.

TAN-452 is an orally active, selective peripherally acting δ-opioid receptor (DOR) antagonist with a K_i of 0.47 nM and a K_b of 0.21 nM. TAN-452 is an antagonist for μ-opioid receptor (MOR; K_i=36.56 nM and K_b=9.43 nM) and κ-opioid receptor (KOR; K_i=5.31 nM and K_b=7.18 nM). TAN-452, a derivative of Naltrindole, demonstrates low brain penetrability and attenuates morphine-induced side effects without affecting pain control.

SB-334867 free base (SB334867A free base) is an excellent, selective and blood–brain barrier permeable orexin-1 (OX1) receptor antagonist, shows selectivity over OX2 (pK_b=7.4), 100-fold over 5-HT_2B, 5-HT_2C with pK_i values of 5.4 and 5.3, respectively. SB-334867 reduces ethanol consumption and inhibits the acquisition of morphine-induced sensitization to locomotor activity in vivo.

PF-06751979 is a potent, brain penetrant, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor with an IC₅₀ of 7.3 nM in BACE1 binding assay.

SRX246 is a potent, BBB-penetrant, highly selective vasopressin 1a (V1a) receptor antagonist (K_i=0.3 nM for human V1a). SRX246 has no interaction at V1b and V2 receptors. SRX246 also displays negligible binding at 64 others receptors classes, including 35 G-proteincoupled receptors. SRX246 can be used for treatment of stress-related disorders.

Ulefnersen sodium (ION363) is an Antisense Oligonucleotide (ASO) directed against the 6th intron of the fused-in sarcoma (FUS) transcript to silence FUS in a non-allele-specific manner. Ulefnersen sodium can reduce postnatal levels of FUS protein in the brain and spinal cord in disease-relevant mouse model of ALS-FUS , delaying motor neuron degeneration. Ulefnersen sodium can be used in the research of Amyotrophic Lateral Sclerosis (ALS) .

PQCA is a highly selective and potent muscarinic M1 receptor positive allosteric modulator. PQCA has an EC₅₀ value of 49 nM and 135 nM on rhesus and human M1 receptor, respectively. PQCA is inactive for other muscarinic receptors. PQCA has potential to reduce the cognitive deficits associated with Alzheimer's disease.

Zagociguat (CY-6463) is an orally active and BBB-permeable soluble guanylate cyclase (sGC) stimulator. Zagociguat can increase cGMP levels, regulate blood pressure, improve neuronal function, reduce inflammatory responses, and exert neuroprotective and cognitive-improving effects. Zagociguat can be used in the research of neurodegenerative diseases.

BMS-986187 is an δ-opioid receptor-selective positive allosteric modulator (PAM) with an EC₅₀ of 0.03 μM and a pK_B of 6.02 (～1 μM). BMS-986187 has no observable PAM activity at the μ-receptor (EC₅₀=3 μM).

Zaloglanstat (ISC-27864; GRC-27864) is a selective, orally active microsomal mPGES-1 inhibitor. Zaloglanstat has an IC₅₀ of 5 nM for human mPGES-1 without significant inhibitory effect on COX-1/2 (IC₅₀ >10 μM). Zaloglanstat blocks the conversion of arachidonic acid metabolite prostaglandin PGH₂ to prostaglandin PGE₂, thereby inhibiting inflammation-related PGE₂ overproduction and reducing inflammatory responses and pain. Zaloglanstat inhibits IL-1β-induced PGE₂ release in A549 cells and human synovial fibroblasts in vitro. Zaloglanstat inhibits PGE2 release in pig and dog whole blood with IC₅₀s of 161 nM and 154 nM, respectively. Zaloglanstat can be used in the study of asthma, osteoarthritis, and neurodegenerative diseases.

Daxdilimab (MEDI7734; VIB7734) is a monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7) that depletes plasmacytoid dendritic cells and reduces IFN1 production by binding to the plasmacytoid dendritic cell-specific surface molecule ILT7 and recruiting effector natural killer cells. Daxdilimab (MEDI7734; VIB7734) can be used for research on systemic lupus erythematosus, systemic sclerosis, and polymyositis.

Adrogolide hydrochloride (ABT-431 hydrochloride) is a chemically stable prodrug that can convert to the dopamine D1 receptor agonist A-86929. Adrogolide hydrochloride ameliorates the MPTP (HY-15608)-induced Parkinson's Disease in marmoset model, reduces the dyskinesias tendency. Adrogolide hydrochloride reverses Risperidone (HY-11018)-induced cognitive deficits in monkey.

Phenibut (β-Phenyl-GABA) is a GABA-B agonist. Phenibut acts as a GABA-mimetic, primarily at GABAB receptors. Phenibut has anxiolytic and nootropic (cognition enhancing) effects.

Phenytoin-d₁₀ is the deuterium labeled Phenytoin. Phenytoin (5,5-Diphenylhydantoin) is a potent Voltage-gated Na+ channels (VGSCs) blocker. Phenytoin has antiepileptic activity and reduces breast tumour growth and metastasis in mice.

SCS (Salicylidene salicylhydrazide) is a potent, allosteric and selective inhibitor of β1-containing GABA_A receptors with an IC₅₀ of 32 nM against α2β1γ1θ by VIPR measurement. SCS is also a chelator of metal ions.