Clozapine N-oxide is the major metabolite of Clozapine and is blood-brain barrier permeable. Clozapine N-oxide is an agonist of DREADDs and activates the DREADD receptors hM3Dq and hM4Di. Clozapine N-oxide is also a dopamine antagonist and selective muscarinic M4 receptor agonist.

hMAO-B-IN-5 is a potent reversible and selective human monoamine oxidase hMAO-B inhibitor (IC50:0.12μM). hMAO-B-IN-5 can cross the blood-brain barrier and can be used in the study of Parkinson's disease. It is a promising compound in the treatment and diagnosis of central nervous system diseases.

DN-1289 is an orally available, blood-brain barrier-crossing, selective and potent inhibitor with an IC50 value of 17 nM for di-leucine zipper kinase (DLK) and 40 nM for leucine zipper-bearing kinase (LZK).DN-1289 significantly inhibited optic nerve crush (ONC)-induced p-c-Jun in a mouse model.

AZD4747 is a selective and potent inhibitor of the mutant GTPase KRASG12C that crosses the blood-brain barrier and has potential antitumor activity for the study of pancreatic and colorectal adenocarcinoma.

Repinotan (BAY x 3702 free base) is an orally active and selective 5-HT1A receptor agonist that crosses the blood-brain barrier (BBB), has neuroprotective activity, antagonizes morphine-induced depression of ventilation in anesthetized rats, and can be used in studies of acute ischemic stroke and traumatic brain injury.

Masupirdine free base (SUVN-502 free base) is an orally available 5-HT6 receptor antagonist that crosses the blood-brain barrier and has a Ki value of 2.04 nM for the human 5-HT6 receptor.Masupirdine free base is potent and selective with multiple targets. Masupirdine free base is highly potent, selective and inhibits multiple targets.Masupirdine free base can be used in the study of neurological disorders such as Alzheimer's disease.

TC-N 22A is a strong, selective, oral active mGlu4 forward allosteric regulator (PAM) that can cross the blood-brain barrier. EC50 expression of TC-N 22A in BHK cells expressing human mGlu4 was 9 nM. TC-N 22A showed very low activity against mGlu 1, 2, 3, 5, and 7 receptors in excitation and forward allosteric models (EC50 >10 μM). TC-N 22A can be used in the study of central nervous system diseases.

LXE408 fumarate is an orally active, non-competitive and kinetoplastid-selective proteasome inhibitor. LXE408 fumarate has an IC50 of 0.04 μM for L. donovani proteasome and an EC50 of 0.04 μM for L. donovani. LXE408 fumarate has a low propensity to cross the blood brain barrier. LXE408 fumarate has the potential for visceral leishmaniasis (VL) research.

(1R,2R)-2-PCCA hydrochloride is a potent, selective, and blood-brain-barrier-crossing GPR88 receptor agonist with an EC50 value of 1140 n in striatal membranes of WT mice.(1R,2R)-2-PCCA hydrochloride can be used to study the central nervous system.

MPT0G211 is a highly selective and orally active HDAC6 inhibitor (IC50=0.291 nM) that has neuroprotective effects and has shown anti-metastatic activity in human breast cancer cells. MPT0G211 has 1,000 times more affinity for HDAC6 than other HDAC subtypes. MPT0G211 can cross the blood-brain barrier and could be used to improve tau phosphorylation and cognitive deficits in Alzheimer's disease models.

SB-277011 hydrochloride (SB-277011A hydrochloride) is a potent, selective, orally active, dopamine D3 receptor (D3R) antagonist that crosses the blood-brain barrier with Ki values of 10.7 nM and 11.2 nM for rodent and human D3R, respectively. 277011 hydrochloride is 80-100 times more selective for D3 receptors than other dopamine receptors, acting on D3 receptors (pKi:8.0), D2 receptors (pKi:6.0), 5-HT1B receptors (pKi<5.2) and 5-HT1D receptors (pKi:5.9).

PF-5274857 (PF-5274857 free base) is an effective and selective hedgehog signaling pathway inhibitor (IC50: 5.8 nM and a Ki: 4.6 nM). PF-5274857 is a potentially attractive clinical candidate for the treatment of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway.PF-5274857 was found to effectively penetrate the blood-brain barrier and inhibit Smo activity in the brain of primary medulloblastoma mice, resulting in improved animal survival rates. PF-5274857 was orally available and metabolically stable in vivo.

SR 57227 hydrochloride(SR 57227A ) is a potent, orally active and selective 5-HT3 receptor agonist. It with ability to cross the blood brain barrier. It has affinities (IC50) varying between 2.8 and 250 nM for 5-HT3 receptor binding sites in rat cortical membranes and on whole NG 108-15 cells or their membranes. Anti-depressant effects.

JDB175, a selective BTK inhibitor with oral bioavailability, demonstrates excellent penetration through the blood-brain barrier. It exhibits potent activity against central nervous system lymphoma in a mouse model, with no apparent toxicity. JDB175 effectively suppresses human lymphoma cell proliferation by inhibiting the BTK signaling pathway, induces cell cycle arrest, and promotes apoptosis[1].

Relamorelin (RM-131) acetate is a pentapeptide ghrelin analog that acts as a selective agonist for the ghrelin/growth hormone secretagogue receptor (GHSR). It exhibits a high affinity for the GHS-1a receptor, with a Ki value of 0.42 nM. Notably, Relamorelin acetate can cross the blood-brain barrier and target the central nervous system. This compound effectively increases growth hormone levels and promotes faster gastric emptying. Due to these properties, Relamorelin acetate holds promise for its potential applications in research related to cachexia, gastroparesis, and gastric/intestinal dysmobility disorders [4] [5].

Dihydroquinoline-pyrazoline DQP-997-74 (compound 2i) is a selective N-methyl-d-aspartate receptor (NMDAR) inhibitor that preferentially targets GluN2C/D subunits, with IC50 values of 0.069 μM and 0.035 μM, respectively, and possesses blood-brain barrier permeability. It enhances its inhibitory potency in a time-dependent manner when combined with the agonist glutamate, reducing epileptogenic events in a murine model of tuberous sclerosis complex (TSC)-induced epilepsy. DQP-997-74 is potentially applicable for the study of NMDAR-related neurological diseases [1].

hMAO-B-IN-4 is a selective, reversible and blood–brain barrier (BBB) penetrable inhibitor of human monoamine oxidase-B (hMAO-B, IC50=0.067 μM, Ki= 0.03 μM, hMAO-A, IC50= 33.82 μM).

ML218 is an orally active, selective, potent, and blood-brain barrier-crossing inhibitor of T-type Ca2+ channels (Cav3.1, Cav3.2, Cav3.3) (IC50 for Cav3.2 and Cav3.3 is 310 nM and 270 nM, respectively).ML218 inhibits the burst activity of neurons in the subthalamic nucleus (STN).

RLX-33 is a potent and selective antagonist of relaxin family peptide 3 (RXFP3) that crosses the blood-brain barrier and also blocks relaxin 3-induced ERK1/2 phosphorylation. RLX-33 can block the increase in food intake induced by the RXFP3 selective agonist R3/I5 in rats.RLX-33 can be used to study the metabolic syndrome.

NCT 501 hydrochloride is a potent and selective ALDH1A1 inhibitor (IC50 = 40 nM). Exhibits >1000-fold selectivity for ALDH1A1 over ALDH3A1, ALDH1B1, ALDH2, HPGD and HSD17β4. Also selective over a panel of 168 GPCRs. Blood-brain barrier permeable.

Frakefamide is unable to penetrate the blood-brain-barrier and enter the central nervous system. Frakefamide TFA is a potent analgesic that acts as a peripheral active μ-selective receptor agonist.

WSD0922-FU is a blood-brain-barrier (BBB) penetrable selective inhibitor of epidermal growth factor receptor (EGFR) and various EGFR mutations, including but not limited to the EGFR variant III (EGFRvIII) mutant form, with potential antineoplastic activity. WSD0922-FU is able to penetrate the BBB and specifically targets, binds to and inhibits EGFR and specific EGFR mutations, which prevents EGFR/EGFR mutant-mediated signaling and leads to cell death in EGFR/EGFR mutant-expressing tumor cells. Compared to other EGFR inhibitors that are not able to penetrate the BBB, WSD0922-FU may have therapeutic benefits in brain tumors, such as glioblastoma (GBM) and metastatic CNS tumors.

JZP-MA-11 is a positron emission tomography (PET) ligand that specifically targets the endocannabinoid α/β-hydrolase domain 6 (ABHD6) enzyme. It exhibits selective inhibition of ABHD6, achieving an IC50 value of 126 nM and is capable of crossing the blood-brain barrier (BBB). The compound, labeled with [18F], demonstrates promising potential for preclinical evaluation in both mice and nonhuman primates (NHP) as a tool for investigating brain ABHD6 activity [1].

WF-47-JS03 is a selective and potent inhibitor of RET kinase that crosses the blood-brain barrier and is more than 500-fold more selective for the kinase insertion domain receptor (KDR).WF-47-JS03 acts on Ba/F3 cells transfected with KIF5B-RET (IC50: 1.7 nM) and LC-2/ad lung cancer cells transfected with CCDC6-RET (IC50: 5.3 nM). cells (IC50: 5.3 nM).

JNK3 Inhibitor-8 is a potent, selective, and orally active inhibitor that can cross the blood-brain barrier, targeting JNK3 with IC50 values of 21 nM for JNK3, 2203 nM for JNK2, and >10000 nM for JNK1. This compound demonstrates significant neuroprotective effects and holds promise for Alzheimer’s disease (AD) research [1].

Frakefamide TFA is a potent analgesic functioning as a μ-selective receptor agonist with peripheral activity. Notably, Frakefamide cannot cross the blood-brain barrier to enter the central nervous system [1] [2].

JNK3 Inhibitor-3 (compound 15g) is a selective, blood-brain barrier permeable, and orally active inhibitor of c-Jun N-terminal kinase 3 (JNK3) with IC50 values of 147.8 nM, 44.0 nM, and 4.1 nM against JNK1, JNK2, and JNK3, respectively. This compound has been shown to significantly enhance memory in mouse models of dementia and is utilized in Alzheimer’s disease research [1].

Frakefamide is a potent analgesic that functions as a peripheral active μ-selective receptor agonist. It cannot penetrate the blood-brain barrier to enter the central nervous system.

TP-050 is a potent, selective NMDAR agonist that is orally active, showing EC50 values of 0.51 µM for GluN2A and 9.6 µM for GluN2D. This compound can cross the blood-brain barrier (BBB), enhancing hippocampal long-term (LTP) potentiation and neuronal signal transmission.

MS48107 is a potent, selective positive allosteric modulator of G protein-coupled receptor 68 (GPR68), demonstrating specificity for GPR68 over closely related proton GPCRs, neurotransmitter transporters, and hERG ion channels. It effectively crosses the blood-brain barrier (BBB) in mice.

Mu opioid receptor antagonist 3 (compound 26) is a potent and selective mu opioid receptor (MOR) antagonist that penetrates the blood-brain barrier (Ki: 0.24 nM, EC50: 0.54 nM). Mu opioid receptor antagonist 2 can be used to study opioid use disorder (OUD).

HDAC6-IN-13 (Compound 35m) is a potent and highly selective orally active inhibitor of HDAC6, with an IC50 of 0.019 μM. It also demonstrates inhibitory activity against HDAC1, HDAC2, and HDAC3, with IC50 values of 1.53 μM, 2.06 μM, and 1.03 μM, respectively. HDAC6-IN-13 exhibits substantial blood-brain barrier permeability and displays anti-inflammatory properties [1].

SKF89976A is a potent GABA uptake inhibitor, which is selective for GAT-1 (IC50 values are 0.13, 550, 944 and 7210 μM for hGAT-1, rGAT-2, hGAT-3 and hBGT-1 respectively). SKF89976A inhibits transport current competitively (Ki = 7 μM) and transmitter-gated current non-competitively (Ki = 0.03 nM). It is able to pass the blood-brain barrier after systemic administration and is active in vivo.

A 1070722 is a potent and selective GSK-3 inhibitor, with a Ki of 0.6 nM for both GSK-3α and GSK-3β. It can penetrate the blood-brain barrier (BBB) and accumulates in brain regions, thus potential for PET radiotracer for the quantification of GSK-3 in bra

VRT-043198, the drug metabolite of VX-765 (Belnacasan), is a potent, selective, and blood-brain barrier permeable inhibitor of the interleukin-converting enzyme/caspase-1 subfamily caspases, displaying Ki values of 0.8 nM for ICE/caspase-1 and 0.6 nM for caspase-4, respectively.

Darigabat (PF-06372865) is an orally active and selective GABAA receptor modulator that crosses the blood-brain barrier and exhibits anxiolytic activity, with Ki values of 2.9 nM, 21 nM, and 134 nM for α2, α1 PAM, and α2 PAM, respectively.Darigabat is used in the study of anxiety disorders and epilepsy.

LEI-401 is a selective and potent NAPE-PLD inhibitor that crosses the blood-brain barrier (IC50: 27 nM).LEI-401 reduces the level of n-acylethanolamines (NAEs) in the brain of free-ranging mice and modulates their emotional behaviour.

SR59230A hydrochloride is a potent, selective, and blood-brain barrier penetrating antagonist of β3-adrenergic receptor(IC50s of 40, 408, and 648 nM for β3, β1, and β2 receptors, respectively).

DZD1516, a potent and selective HER2 inhibitor (IC50 = 0.56 nM), demonstrates good blood-brain barrier permeability and exhibits antitumor activity in both central nervous system (CNS) and subcutaneous xenograft mouse models [1].

CHDI 00484077, a potent and selective class IIa histone deacetylase (HDAC) inhibitor, demonstrates significant efficacy with IC50 values ranging from 10-30 nM in vivo and specific activity at 0.01 nM and 0.04 nM in HEK293 and Jurkat cells, respectively. It exhibits a 150-fold selectivity for class IIa over class I/IIb HDACs in cellular environments, indicating a high degree of specificity. Additionally, CHDI 00484077 is orally bioavailable and capable of crossing the blood-brain barrier (CNS penetrant).

MPT0G211 mesylate is a powerful and selective HDAC6 inhibitor (IC50 = 0.291 nM), with high oral bioavailability. It exhibits remarkable selectivity for HDAC6 over other HDAC isoforms (>1000-fold selectivity). Additionally, MPT0G211 mesylate can effectively cross the blood-brain barrier. In preclinical studies using an Alzheimer's disease model, MPT0G211 mesylate has shown promising results in reducing tau phosphorylation and cognitive deficits. Furthermore, this compound exhibits anti-metastatic and neuroprotective effects, making it a potential candidate for anticancer interventions. [1] [2] [3].

Orvepitant maleate is an effective, selective, and well-tolerated neurokinin-1 receptor (NK-1) antagonist (pKi: 10.2 for human neurokinin-1 receptor). Orvepitant maleate has the potential for depressive disorder and chronic refractory cough (CRC) treatmen

CB1-IN-2 (Compound 4g) is a potent and selective inhibitor of the CB1 receptor, exhibiting an IC50 value of 0.644 μM. This compound possesses the ability to penetrate the blood-brain barrier and has the potential to induce central nervous system (CNS) side effects similar to Rimonabant [1].

Fenoldopam hydrochloride is a selective D1-like dopamine receptor partial agonist. It acts as a vasodilator in vivo and does not readily cross the blood-brain barrier. Fenoldopam HCl is also an α2-adrenoceptor antagonist in vitro.

Nepicastat (SYN117) is a selective, potent, and orally active dopamine-beta-hydroxylase inhibitor which can cross the blood-brain barrier (BBB). Nepicastat (SYN117) produces concentration-dependent inhibition of bovine and human dopamine-beta-hydroxylase with IC50s of 8.5 nM and 9 nM [1] [2] [3].

Withaphysalin D, isolated from water lilies, is a selective antagonist for the N-methyl-D-aspartate receptor (NMDAR) containing GluN2B with neuroprotective properties. This compound is capable of crossing the blood-brain barrier [1].

BuChE-IN-7 is a selective inhibitor targeting human butyrylcholinesterase (hBuChE) and equine butyrylcholinesterase (eqBuChE), demonstrating IC50 values of 40 nM and 80 nM, respectively. Demonstrating the ability to penetrate the blood-brain barrier, BuChE-IN-7 enhances cognitive functions and specifically augments situational and phobic memory, exhibiting a preference for novelty.

SRI-29132 is potent; highly permeant of the blood-brain barrier; and selective for LRRK2 kinase activity, therefore effective in attenuating pro-inflammatory responses in macrophages and in rescuing neurite retraction phenotypes in neurons.

SL327 is a selective inhibitor for MEK1/2 with IC50 of 0.18 μM/0.22 μM; able to transport through the blood-brain barrier.

Monoamine Oxidase B inhibitor 2 is a potent, reversible, orally active and selective inhibitor of monoamine oxidase B (MAO-B) (IC50 = 1.33 nM) which can across the blood-brain barrier (BBB). Monoamine Oxidase B inhibitor 2 shows antioxidant and anti-neuroinflammatory activities which can be used in the study of Parkinson’s disease [1].