bbb

Spermine (N3BBB), a click chemistry reagent with an azide group, facilitates diverse biochemical studies [1].

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.

FITC-Dextran (MW 2,000,000) is a fluorescent dye-based compound that can be used for short cycle durations to outline blood vessels.FITC-Dextran (MW 2,000,000) is involved in the quantification of BBB leakage, and can be used in conjunction with a confocal microscope to visualize blood-brain-barrier leakage.

BuChE-IN-TM-10 (TM-10) is a potent inhibitor of butyrylcholinesterase (BuChE), exhibiting an IC50 of 8.9 nM. It effectively inhibits and disaggregates self-induced Aβ aggregation, displays significant antioxidant activity, and demonstrates substantial penetration through the blood-brain barrier (BBB). TM-10 holds promise as a potential treatment for Alzheimer’s disease.

Baclofen hydrochloride (4-amino-3-(4-chlorophenyl)butanoic acid hydron chloride) is a GAMMA-AMINOBUTYRIC ACID derivative that is a specific GABA-B RECEPTORS agonist. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.

4-Hydroxyantipyrine is formed during oxidative deamination of aminopyrine.

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.

Nitrobenzylthioinosine (NBMPR) is an inhibitor of ENT1 transporter that binds to ENT1 transporter with high affinity.

Pramipexole dihydrochloride hydrate (Mirapex) is the hydrochloride salt of pramipexole, a benzothiazole derivative. As a nonergot dopamine agonist, pramipexole binds to D2 and D3 dopamine receptors in the striatum and substantia nigra of the brain.

Carbetocin is an obstetric drug used to control postpartum hemorrhage and bleeding after giving birth.

Perhexiline is an orally active inhibitor of CPT1 and CPT2 that reduces fatty acid metabolism. Perhexiline can cross the blood-brain barrier (BBB) and exhibits anti-tumor activity. Perhexiline induces mitochondrial dysfunction and apoptosis in hepatocytes. Therefore, Perhexiline can be used in cancer and cardiovascular disease research [1] [2] [5].

J-147 is an experimental drug with reported effects against both Alzheimer's disease and ageing in mouse models of accelerated aging. It is a curcumin derivative and a potent neurogenic and neuroprotective drug candidate initially developed for the treatment of neurodegenerative conditions associated with aging that impacts many pathways implicated in the pathogenesis of diabetic neuropathy.

MAGL-IN-4 (His121 ARG57) is one of the monoacylglycerol lipase (MAGL) inhibitors in central nervous system-related diseases.

AS057278 (3-Methylpyrazole-5-carboxylic acid) is an D-amino acid oxidase (DAAO) inhibitor.

4',4''-Dihydroxyanigorootin is a natural product from Musa cv. Thepanom (BBB).

P7C3-A20 is a derivative of P7C3 that has proneurogenic and neuroprotective activity.

4-Hydroperoxyifosfamide is an anticancer agent capable of penetrating the blood-brain barrier (BBB) [1].

Gadobutrol is a medicinal product used in diagnostic magnetic resonance imaging (MRI) in adults and children. It provides contrast enhancement during cranial, spinal, breast, or other investigations. In the central nervous system, Gadobutrol works by high

Substance P (3-11), an SP fragment peptide capable of crossing the blood-brain barrier (BBB), induces contraction in guinea pig ileum and facilitates chemotaxis in human monocytes [1] [2] [5].

OY-201 is a promising anti-ischemic stroke agent capable of crossing the blood-brain barrier (BBB). It demonstrates significant safety and neuroprotective activity in in vitro and in vivo models [1].

hAChE-IN-5 (compound 49) is a dual inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBuChE), exhibiting inhibitory potency with IC50 values of 0.17 μM for both enzymes. Additionally, it demonstrates potent glycogen synthase kinase 3 beta (GSK3β) inhibition with an IC50 of 0.21 μM. The compound is an effective inhibitor of tau protein and Aβ1-42 peptide self-aggregation. It can virtually bind the peripheral anionic site (PAS), preventing amyloid-beta (Aβ)-induced neurotoxicity. hAChE-IN-5's ability to cross the blood-brain barrier (BBB) underpins its utility in the development of multitargeted anti-Alzheimer’s agents [1].

3-Acetyldeoxynivalenol is a trichothecene mycotoxin deoxynivalenol acetylated derivative and a blood-brain barrier (BBB) permeable mycotoxin.

WAY-649123 is an active molecule that exhibits (in vitro) antagonistic properties against (alpha-1A adrenergic receptors), with a (pKi) of 8.9. It also demonstrates a 70-fold selectivity over (alpha-1B) and 100-fold selectivity over (alpha-1D) subtypes. This compound has been shown to cross the blood-brain barrier (BBB) effectively in preclinical trials. Furthermore, WAY-649123 exhibits a high level of oral bioavailability and a favorable pharmacokinetic profile, making it a potential candidate for clinical development targeting conditions associated with (alpha-1A) receptors.

Phoenixin-14 TFA (PNX-14) is a blood-brain barrier (BBB)-penetrable neuropeptide with anxiolytic, cardioprotective, and neuroprotective properties. It modulates pituitary gonadotrophin release by enhancing gonadotropin-releasing hormone (GnRH) receptor mRNA expression and promotes insulin secretion. Additionally, PNX-14 TFA offers protection against ischemia/reperfusion (IR) injury in mice and combats oxidative stress by diminishing reactive oxygen species (ROS) and elevating glutathione (GSH) levels [1] [2] [3].

Angiopep-Bim BH3 hydrochloride, a peptode that penetrates the blood-brain barrier (BBB), may serve as a tool to study the permeability of central nervous system (CNS) therapeutics [1].

2-Methoxystypandrone displays an immunomodulatory effect in a cellular model, it blocks inflammatory responses by impairing NF-κB signaling to limit the inflammation and oxidative stress for preservation of BBB integrity. 2-Methoxystypandrone concomitant

high affinity agonist of the translocator protein

Rabies Virus Glycoprotein (TFA) is a kind of by the Rabies Virus Glycoprotein 29 - amino acid derived cell penetrating peptides, it can pass the blood brain barrier (BBB) into the brain cells.

AChE/BuChE/MAO-B-IN-2 (compound 4b) is a potent inhibitor of AChE, BuChE, and hu MAO-B, with respective IC50 values of 5.3 μM, 12.4 μM, and 1.9±0.08 μM, indicating good in vitro blood-brain barrier (BBB) permeability. It is effective in reducing excessive AChE and BuChE levels associated with Alzheimer's disease (AD) and holds potential for use in anti-Alzheimer's research [1].

NT1-014B, a potent NT1-lipidoid encapsulated amphotericin B (AmB), integrates NT-lipidoids into blood-brain barrier (BBB)-impermeable lipid nanoparticles (LNPs), enabling them to cross the BBB. This compound enhances brain delivery via intravenous injection [1].

QM-FN-SO3 is a blood-brain barrier (BBB)-penetrable, near-infrared (NIR) probe with aggregation-induced emission (AIE) activity, specifically designed for the detection of Aβ plaques. It exhibits ultra-high signal-to-noise (S/N) ratio, binding affinity, and high-performance NIR emission, making it suitable for in vivo detection of Aβ plaques [1].

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated inhibitor of HDAC6 (IC50= 0.025 μM). HDAC6-IN-5 inhibits Aβ 1-42 self-aggregation and AChE, with IC 50s of 3.0 and 0.72 μM. HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

Ioversol (MP-328) is a nonionic iodinated contrast agent.

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.

sEH/AChE-IN-3 (15) serves as a dual inhibitor targeting both soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE), demonstrating potent activity and the ability to cross the blood-brain barrier (BBB). It exhibits IC50 values of 0.4 nM for human sEH (hsEH), 1.94 nM for human AChE (hAChE), 615 nM for human butyrylcholinesterase (hBChE), 4.3 nM for mouse sEH (msEH), and 2.61 nM for mouse AChE (mAChE), indicating its efficacy across these enzymes.

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.

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].

NU223612 is a potent PROTAC (PROTACs) specifically targeting and degrading indoleamine 2,3-dioxygenase 1 (IDO1) (Indoleamine 2,3-Dioxygenase (IDO)) via CRBN-mediated proteasomal degradation, demonstrating a binding affinity (Kd) of 640 nM for IDO1 and 290 nM for CRBN. Importantly, NU223612 is capable of crossing the blood-brain barrier (BBB) [1].

HDAC6-IN-6 (compound 6a) is a potent inhibitor of HDAC6 that can penetrate BBB with an IC50 value of 0.025 μM. HDAC6-IN-6 has potent inhibitory activity against AChE and Aβ 1-42 self-aggregation with IC50 values of 0.72 and 3.0 μM. HDAC6-IN-6 can enhance the outgrowth of neurite without significant neurotoxicity [1].

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.

NT1-O12B, an endogenous neurotransmitter-derived lipidoid (NT-lipidoid), serves as a highly efficient carrier for enhancing the transportation of various blood-brain barrier (BBB)-impermeable cargos to the brain. Incorporating NT1-O12B into BBB-impermeable lipid nanoparticles (LNPs) enables these LNPs to effectively traverse the BBB. In addition to enabling cargo passage through the BBB, NT-lipidoid formulations facilitate efficient delivery of the cargo into neuronal cells for purposes such as functional gene silencing or gene recombination[1].

NMDA receptor antagonist 4 (IIc) is an uncompetitive, voltage-dependent, orally active NMDAR blocker, with an IC 50 of 1.93 μM. NMDA receptor antagonist 4 shows a positive predicted blood-brain-barrier (BBB) permeability, and can be used in Alzheimer's disease research[1].

Neuroinflammatory-IN-2 (compound 7i) is a potent anti-neuroinflammatory agent, capable of acting on MAO-B (IC50: 10.30 μM). Neuroinflammatory-IN-2 inhibits 96.33% of Aβ1-42 aggregation at 25 μM. Neuroinflammatory-IN-2 exhibits neuroprotective activity in H2O2-induced PC-12 cell injury. Neuroinflammatory-IN-2 can be used to study Alzheimer's disease.

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

Azeliragon (TTP488) is an antagonist at the Receptor for Advanced Glycation End products; is evaluated as a potential treatment for patients with mild-to-moderate Alzheimer_acute_s disease (AD).

(+)-Bicuculline methiodide is a γ-aminobutyric acid type A (GABAA) receptor blocker that crosses the rat blood-brain barrier (BBB) and blocks epileptogens, which can be used to study neurological disorders such as epilepsy. (+)-Bicuculline methiodide reduces liver injury in septic rats.

Cnidilin (Knidilin) is found in association with Angelica dahurica roots, has high BBB permeability and has pharmacokinetic potential in the treatment of CNS disorders.

Baclofen (Lioresal) is a synthetic chlorophenyl-butanoic acid derivative used to treat spasms due to spinal cord damage and multiple sclerosis, muscle-relaxing Baclofen acts as a gamma-aminobutyric acid (GABA) agonist specific for GABA-B receptors. It acts at spinal and supraspinal sites, reducing excitatory transmission.

Biphalin TFA is an opioid peptide analog that penetrates the blood-brain barrier (BBB) and encompasses two active enkephalin pharmacophores. It exhibits high affinity for opioid receptors and demonstrates analgesic effects in acute, neuropathic, and chronic animal pain models. Additionally, Biphalin TFA possesses antiviral, antiproliferative, anti-inflammatory, and neuroprotective properties [1].

TfR-T12 TFA, a transferrin receptor (TfR)-binding peptide capable of crossing the blood-brain barrier (BBB), exhibits nanomolar (nM) binding affinity [1] [2].

Cabazitaxel (taxoid XRP6258) is a taxane and antineoplastic agent which is currently used in the therapy of castration-resistant metastatic prostate cancer after failure of docetaxel.