Neurological Disease

DMNPE-4 AM-caged-calcium, photolabile analogues of EGTA, is an extremely effective Ca²⁺ selective cage, with a K_d for Ca²⁺ of 48 nM and 19 nM at pH 7.2 and pH 7.4, respectively. DMNPE-4 AM-caged-calcium has a lower affinity for Ca²⁺ (K_d=~2 nM) after photolysis.

U-89843A (PNU-89843) hydrochloride is a GABAA receptors positive allosteric modulator (PAM). U-89843A hydrochloride enhances GABA-induced Cl^- currents in the α1β2γ2, α3β2γ2 and α6β2γ2 subtypes. U-89843A hydrochloride shows antioxidant and sedative effects.

SJ44236 is a BET PROTAC degrader with activity against BRD2, BRD3 and BRD4 (DC₅₀ = 127 pM). SJ44236 induces ubiquitination and proteasomal degradation by forming a ternary complex with BET proteins and CRBN-DDB1. SJ44236 downregulates c-Myc, upregulates p53 and reduces cancer cell viability. SJ44236 can be used for the research of leukemia and medulloblastoma.

MDL 29913, a cyclic pseudopeptide, is a competitive NK₂ tachykinin receptor selective antagonist, with a pA₂ of 8.66.

(-)-P7C3-S243 is an orally active, blood-brain barrier permeable neuroprotective agent. (-)-P7C3-S243 binds to μ-opioid Receptor and TSPO. (-)-P7C3-S243 inhibits the premature apoptosis death of newborn hippocampal neurons, protects mature nigral dopaminergic neurons, promotes neuronal survival and prevents cognitive impairment. (-)-P7C3-S243 ameliorates depression-like behaviors in rat models. (-)-P7C3-S243 is applicable to research related to Parkinson's disease and Alzheimer's disease.

Propoxur-d₃ is the deuterated form of Propoxur (HY-B0916). Propoxur is a reversible, competitive, orally active AChE inhibitor that can cross the blood-brain barrier. Propoxur inhibits AChE activity to induce neurotoxicity, while promoting MMP-2 expression and enhancing tumor cell migration and invasion by inducing intracellular ROS generation and activating the ERK/Nrf2 signaling pathway. On the one hand, Propoxur inhibits AChE, leading to acetylcholine accumulation and causing neurological dysfunction; on the other hand, it promotes Nrf2 nuclear translocation through ROS-dependent ERK1/2 phosphorylation, and upregulates MMP-2 and other invasion-related proteins. Propoxur is also a carbamate insecticide used to combat turf, forestry, and household pests.

GR231118 TFA, an analogue of the C-terminus of neuropeptide Y, is a potent , competitive and relative seletive antagonist at human neuropeptide YY receptor with a pK_i of 10.4. GR231118 a potent agonist at the human neuropeptide YY4 receptor (pEC₅₀=8.6; pK_i=9.6) and a weak agonist at the human and rat neuropeptide Y Y2 and Y5 receptors. GR231118 also has high affinity for the mouse neuropeptide YY6 receptor (pK_i= 8.8).

SH-11037 is a potent inhibitor of soluble epoxide hydrolase (sEH) and docks to the substrate binding cleft in the sEH hydrolase domain. SH-11037 dose-dependently suppresses angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. SH-11037 reduces choroidal neovascularisation lesion volume in the laser-induced CNV mouse model. SH-11037 synergises with anti-VEGF treatments in vitro and in vivo. SH-11037 induces G2/M phase blockade and retains retinal endothelial cell viability at active concentrations without overt toxicity. SH-11037 can be used for the research of retinal neovascularization and ocular neovascularization.

Ro 17-1812 is a benzodiazepine receptor partial agonist with anticonvulsant effect.

Fenyramidol is an Aminopyridine derivative. Fenyramidol can be used as a moderately potent, non-narcotic muscle relaxant with concomitant analgesic activity.

Lomerizine is an antagonist of L- and T-type voltagegated calcium channels.

Pozanicline (ABT-089) selectively activate neuronal nicotinic acetylcholine receptor (nAChR) subtypes, is a novel cholinergic agent that is a partial agonist at α4β2* nAChRs (K_i=16 nM) and shows high selectivity for α6β2* and α4α5β2 nAChR subtypes, the binding affinity (K_i, rat) for Pozanicline to [³H] cytisine sites is 16.7 nM. Pozanicline reverses nicotine withdrawal-induced cognitive deficits, may be an effective component of novel therapeutic strategies for nicotine addiction.

PG-911 is a full MC5R agonist (EC₅₀ = 0.031 nM for hMC5R). PG-911 is also a full antagonist at the hMC3R and the hMC4R (K_b: 0.38 nM and 0.17 nM, respectively). PG-911 can be used in the research of neurological disorders.

α-Synuclein inhibitor 5 (compound 4aa) is a potent and BBB-penetrated inhibitor of α-Synuclein (α-Syn) aggregation, with an IC₅₀ of 1.22 μM and inhibition ratio at 30 μM of 94.3%.

PF-1010 is a CD73 inhibitor with an IC₅₀ ranging from 101 to 1000 nM. PF-1010 blocks the interaction between CD73 protein and its substrate, and inhibits the enzymatic activity of CD73. PF-1010 is applicable to the research of cancer, infectious diseases, autoimmune diseases and neurodegenerative diseases.

Oxeladin is an orally active and brain-penetrant cough suppressant as well as a selective sigma 1 receptor agonist (K_i = 25 nM). Oxeladin can be used for pulmonary diseases and stroke research.

ECPLA, a lysergamide lysergic acid diethylamidean (LSD) analog, is a potent 5-HT2A agonist (EC₅₀ of 14.6 nM) for Gq-mediated calcium flux. ECPLA has high affinity for most serotonin receptors, α2-adrenoceptors, and D2-like dopamine receptors.

TAAR1 agonist 1 (compound 6E) is a potent TAAR1 agonist with a potent TAAR1-Gs/Gq dual-pathway activation property. TAAR1 agonist 1 significantly alleviates MK-801-induced schizophrenia-like cognitive phenotypes.

3,4-Methylenedioxy PV8 hydrochloride is a pyrrolidine-containing synthetic drug derivative.

Dendrobine-N-oxide is a dendrobine-type sesquiterpene alkaloid. It is isolated from Dendrobium nobile. Dendrobine-N-oxide inhibits neuroinflammation, reduces β-Amyloid accumulation, enhances the expression of neurotrophic factors, suppresses the hyperphosphorylation of Tau protein, and exerts anti-neuronal Apoptosis effects. Dendrobine-N-oxide shows no anticancer activity against colon cancer and pancreatic adenocarcinoma. It is used in research on neurodegenerative diseases.