parkinson’s disease

MPTP hydrochloride is a precursor of MPP+, a dopamine neurotoxin with blood-brain barrier permeability. MPTP hydrochloride is toxic to dopaminergic neurons, which can lead to Parkinson's disease, and is widely used in the construction of animal models of Parkinson's disease.

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

Safranal is the special volatile aroma compound of saffron

ST 1535 is a potent and orally active antagonist of the A2A adenosine receptor, exhibiting antiparkinsonian activity and antitremorigenic effects, with potential for Parkinson’s disease research.

SynuClean-D (SC-D) is an α-synuclein aggregation inhibitor that prevents fibril propagation, disrupts mature amyloid fibrils, and abolishes dopaminergic neuron degeneration in an animal model of Parkinson’s disease.

BD-AcAc 2 (Ketone Ester) is a ketone monoester and can be used as a source of oral nutritional ketones. BD-AcAc 2 can elevate plasma levels of acetoacetate and β-hydroxybutyrate, blood Na+, blood glucose levels and blood creatinine levels after oral administration in mice. BD-AcAc 2 can partly prevent muscle weakness in septic mice. BD-AcAc 2 exhibits potential to improve endurance and exercise performance in animal body. BD-AcAc 2 can also be used to research diabetes or Parkinson’s disease.

Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride) is an neurotransmitter dopamine antagonist.

GYY4137 (GYY 4137 morpholine salt) is a novel water-soluble and slow releasing H2S donor with vasodilator and antihypertensive activity. GYY4137 also exhibits anti-inflammatory and anticancer activity.

1. Sinapine, an alkaloid from seeds of the cruciferous species, can be used as an effective natural compound for chemo-resistance. 2. Sinapine has antioxidant and radio-protective activities.

Oxidopamine hydrobromide (6-OHDA hydrobromide) is a neurotransmitter dopamine antagonist.

ELN484228 is a α-synuclein blocker. α-synuclein is a key protein in Parkinson’s disease.

Ibiglustat (L-Malic acid) (Ibiglustat L-Malic acid) is a selective, brain-penetrant, and allosteric inhibitor of glucosylceramide synthase. Ibiglustat (L-Malic acid) can be used in studies about PD Parkinson’s disease, SRT in Fabry’s and Gaucher’s.

Diphenylpyraline hydrochloride (4-Diphenylmethoxy-1-methylpiperidine hydrochloride) is used in the treatment of Parkinsonism.It is a first-generation antihistamine with anticholinergic effects, functions as a dopamine reuptake inhibitor.

UCM-1306 is a potent and orally active allosteric modulator (PAM) of the human dopamine D1 receptor. It increases the maximal effect of endogenous dopamine (DA) in both human and mouse D1 receptors. UCM-1306 could improve motor symptoms and address key comorbid cognitive impairment associated with long-term Parkinson's disease (PD).

ML-193 (CID 1261822) is a potent and selective GPR55 antagonist (IC50: 221 nM) with over 27-fold selectivity for GPR55 over GPR35, CB1, and CB2. It can ameliorate motor and sensorimotor deficits in Parkinson’s disease (PD) rats.

YTX-465 is an inhibitor of both stearoyl-CoA desaturase(IC50s = 39 nM) and Ole1 (IC50s = 30.4 μM).

JH-II-127 is an oral inhibitor of leucine-rich repeat kinase 2 (LRRK2), targeting WT LRRK2, G2019S LRRK2, and A2016T LRRK2 with IC50 values of 6.6 nM, 2.2 nM, and 47.7 nM, respectively.

HG-10-102-01 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2, IC50 of 20.3 nM).

AMK is an active metabolite of the neurohormone melatonin .1,2,3,4It is formed from melatoninviathe metabolic intermediate AFMK that is then deformylated by catalase or formamidase.5,6AMK scavenges singlet oxygenin vitrowhen used at a concentration of 200 μM.1It inhibits the epinephrine- and arachidonic acid-induced production of prostaglandin E2and PGD2in ovine seminal vesicle microsomes in a concentration- and time-dependent manner, as well as LPS-induced increases in COX-2 levels in RAW 264.7 macrophages when used at a concentration of 500 μM.2,3AMK (20 mg/kg) decreases MPTP-induced increases in lipid peroxidation in the cytosol and mitochondria from substantia nigra and striatum in a mouse model of MPTP-induced Parkinson’s disease.4 1.Schaefer, M., and Hardeland, R.The melatonin metabolite N1-acetyl-5-methoxykynuramine is a potent singlet oxygen scavengerJ. Pineal Res.46(1)49-52(2009) 2.Kelly, R.W., Amato, F., and Seamark, R.F.N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesisBiochem. Biophys. Res. Commun.121(1)372-379(1984) 3.Mayo, J.C., Sainz, R.M., Tan, D.-X., et al.Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophagesJ. Neuroimmunol.165(1-2)139-149(2005) 4.Tapias, V., Escames, G., López, L.C., et al.Melatonin and its brain metabolite N1-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian miceJ. Neurosci. Res.87(13)3002-3010(2009) 5.Tan, D.-X., Manchester, L.C., Reiter, R.J., et al.Melatonin directly scavenges hydrogen peroxide: A potentially new metabolic pathway of melatonin biotransformationFree Radic. Biol. Med.29(11)1177-1185(2000) 6.Hirata, F., Hayaishi, O., Tokuyama, T., et al.In vitro and in vivo formation of two new metabolites of melatoninJ. Biol. Chem.249(4)1311-1313(1974)

NMDA receptor antagonist 2 is a highly potent and orally active NR2B subtype-selective antagonist of the N-methyl-D-aspartate (NMDA) receptor, with an IC50 of 1.0 nM and a Ki value of 0.88 nM. This compound is valuable in scientific investigations of neuropathic pain and Parkinson’s disease.

Anhydrosafflor yellow B ((2S,3S)-6,7-dihydroxy-5-[(2E)-3-(4-hydroxyphenyl)prop-2-enoyl]-2-[(1S,2R,3R)-1,2,3,4-tetrahydroxybutyl]-3-{2,3,4-trihydroxy-5-[(2E)-3-(4-hydroxyphenyl)prop-2-enoyl]-6-oxo-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]cyclohexa-1,4-dien-1), isolated from Carthamus tinctorius, inhibits ADP-induced platelet aggregation, exhibits significant anti-oxidative effects in vitro, and possesses certain activity against H2O2-induced cytotoxicity.

Valiglurax (VU2957), also known as VU0652957 and VU2957, is a potent, selective, CNS penetrant, and orally bioavailable mGlu4 PAM. VU2957 possessed attractive in vitro and in vivo pharmacological and DMPK properties across species. VU2957 was evaluated as a preclinical development candidate for the treatment of Parkinson’s disease.

WAY-358981 is an active molecule. (R)-Amino(2,3-dihydro-1-benzofuran-3-yl)acetic acid, known as D-(-)-(1,3-Dioxolan-2-yl)phenicylamine hydrochloride (1:1), is a selective dopamine D3 receptor antagonist often used in the studies of conditions such as substance use disorder, schizophrenia, and Parkinson’s disease [PubChem].

(Rac)-BL-918 is the racemate of BL-918, a potent activator of UNC-51-like kinase 1 (ULK1) with an EC50 of 24.14 nM, inducing cytoprotective autophagy for Parkinson’s disease treatment [1].

GOAT-IN-1 is an inhibitor of ghrelin O-acyltransferase (GOAT) that may be useful for the prophylaxis or treatment of diabetes, hyperlipidemia, non-alcoholic fatty liver, Alzheimer's disease, Parkinson's disease, cerebrovascular dementia, and cerebral infarction.

VU0410150, a pyrrylarylsulfone containing compound, has been found to be a mGluR4-positive allosteric modulator and has been evaluated as a potential drug for the treatment of Parkinson’s disease.

α-Synuclein inhibitor 8 effectively impedes α-Synuclein aggregation and disaggregation with an IC50 of 2.5 µM, demonstrating substantial reduction in neuronal inclusion formation, which contributes to reparative effects in damaged neurons and symptomatic improvement in Parkinson’s disease (PD)-like models. The compound also exhibits high antioxidant activity and low cytotoxicity [1].

α-Conotoxin PIA TFA, targeting nicotinic acetylcholine receptor (nAChR) subtypes with α6 and α3 subunits, acts as an antagonist. This compound shows promise for research into Parkinson’s disease and schizophrenia [1].

MAO-IN-4 (Compound 2l), a monoamine oxidase (MAO) inhibitor, demonstrates IC50 values of 0.07 μM for MAO-A and 0.75 μM for MAO-B. This compound is utilized in studying depression and Parkinson’s disease (PD) [1].

6-(1-Hydroxyethyl)-5,6-dihydrochelerythrine, an alkaloid, significantly alters the characteristics of early endosomes, mitochondria, and autophagosomes in Parkinson's Disease patient-derived olfactory cells [1].

α-Synuclein 4554W, previously identified through intracellular library screening, is an inhibitor of α-Synuclein (aSyn) aggregation and its associated toxicity. This compound, comprising GIVNGVKA sequences, effectively reduces fibril formation in aSyn mutants associated with Parkinson’s disease [1].

Sinapine hydroxide, an alkaloid derived from the seeds of cruciferous plants, demonstrates a variety of beneficial properties including anti-inflammatory, anti-oxidant, anti-tumor, anti-angiogenic, and radio-protective effects. Additionally, it acts as an inhibitor of acetylcholinesterase (AChE), making it valuable for researching neurodegenerative conditions such as Alzheimer’s disease, ataxia, myasthenia gravis, and Parkinson’s disease[4].

HUP-55 is a prolyl endopeptidase inhibitor with an IC50 of 5 nM, shown to mitigate α-synuclein dimerization in Neuro2a cells, stimulate autophagy in HEK293 cells, and lower hydrogen peroxide-evoked reactive oxygen species (ROS) production in SH-SY5Y cells at a 10 µM concentration. Additionally, administration of HUP-55 at a dosage of 10 mg/kg reduces ipsilateral paw use and diminishes striatal oligomeric α-synuclein concentrations in a Parkinson’s disease mouse model, which is induced through adenoviral vector-mediated overexpression of α-synuclein (AAV-αSyn).

Sinapine Thiocyanate, is a derivative of Sinapine (S486605), an alkaloidal amine found in black mustard seeds. It is the choline ester of Sinapic Acid (S486800). It is also a phenolic-chloine conjugates, acting as anti-oxidants and acetylcholinesterase inhibitors, that can be used for the treatment of Alzheimer's disease (AD).

BL-918 is a potent activator of UNC-51-like kinase 1 (ULK1) with an EC50 of 24.14 nM.

Dyrk1A-IN-3 (Compound 8b) is a highly selective inhibitor of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) with a high binding affinity (IC50 of 76 nM). Dyrk1A-IN-3 can be used in neurodegenerative disorders research, such as Alzheimer’s Disease, Huntington’s Disease, and Parkinson’s Disease [1].

Glucocerebrosidase-IN-1 (compound 11a) hydrochloride is a potent and selective glucocerebrosidase (GCase) inhibitor with IC50 of 29.3 μM and Ki of 18.5 μM, used in the research of Gaucher disease (GD) and Parkinson’s disease (PD) [1].

Glucocerebrosidase-IN-1 (compound 11a) is a potent and selective GCase (glucocerebrosidase) inhibitor, with an IC50 of 29.3 μM and a Ki of 18.5 μM. Due to GCase involvement in pathological disorders consequent to enzyme deficiency, Glucocerebrosidase-IN-1 can be used for research of Gaucher disease (GD) and Parkinson's disease (PD)[1].

MAO-B-IN-15 is a selective MAO-B inhibitor (IC50 = 13.5 μM) that forms π-π interactions with the Tyr 326 residue, and it can be utilized in Parkinson’s disease research[1].

Monoamine Oxidase B inhibitor 2 is a potent, reversible, orally active, and selective inhibitor of monoamine oxidase B (MAO-B) with an IC50 of 1.33 nM, capable of crossing the blood-brain barrier (BBB). It exhibits antioxidant and anti-neuroinflammatory activities and is useful in the study of Parkinson’s disease [1].

Neoechinulin C, an alkaloid in the echinulin class of indolediketopiperazine, shields neuronal cells from paraquat-induced damage in a Parkinson’s disease model [1].

Oxybuprocaine hydrochloride (Oxybuprocaine HCl), a local anesthetic, is used especially in otolaryngology and ophthalmology.

4A7C-301, a Nurr1 agonist, exhibits potent neuroprotective effects in vitro and markedly mitigates neuropathological abnormalities while enhancing motor and olfactory functions in male mouse models with AAV2-mediated α-synuclein overexpression. This compound is applicable in Parkinson’s disease research [1].

hMAO-B MB-COMT-IN-2 is a dual inhibitor of MAO-B MB-COMT with IC50s of 4.27 μM and 2.69 μM for hMAO-B and MB-COMT, respectively. hMAO-B MB-COMT-IN-2 protects cells from oxidative damage and can be used in neurodegeneration disease research, such as Parkinson’s Disease (PD) [1].

Dityrosine, an oxidation product of protein formed through the intermolecular cross-linking of tyrosyl radicals from the reactive oxygen species (ROS) and tyrosine interaction, is associated with decreased hippocampal expression of NMDA receptor subunits Nr1, Nr2a, and Nr2b when administered intragastrically at 320 µg/kg per day, leading to memory impairments in mice as evidenced by their performance in a novel object recognition test. Additionally, it raises fasting blood glucose levels while reducing plasma insulin levels and the pancreatic expression of insulin synthesis-related genes Ins2, Pdx1, and MafA. Increased dityrosine levels have been positively linked to a range of diseases, including autism spectrum disorder, cataracts, Alzheimer’s disease, Parkinson’s disease, atherosclerosis, and cystic fibrosis.

PBT434 methanesulfonate is an orally active, potent α-synuclein aggregation inhibitor with the ability to cross the blood-brain barrier. Acting as an iron chelator, it modulates transcellular iron trafficking, inhibits iron-mediated redox activity, and prevents iron-mediated aggregation of α-synuclein. PBT434 methanesulfonate also safeguards against the loss of substantia nigra pars compacta neurons (SNpc), showing promise for Parkinson’s disease (PD) research.

MLi-2 is a structurally novel, highly potent, and selective LRRK2 kinase inhibitor with central nervous system activity. MLi-2 exhibits exceptional potency in a purified LRRK2 kinase assay in vitro (IC50 = 0.76 nM), a cellular assay monitoring dephosphorylation of LRRK2 pSer935 LRRK2 (IC50 = 1.4 nM), and a radioligand competition binding assay (IC50 = 3.4 nM).

XL01126, a potent degrader of LRRK2, exhibits DC50 values of 14 nM (G2019S LRRK2) and 32 nM (WT LRRK2), respectively. It has the ability to cross the blood-brain barrier, making it a viable degrader probe for Parkinson’s disease research. This compound is instrumental in exploring the non-catalytic and scaffolding functions of LRRK2 [1].