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.

BI-4732 is a potent, highly BBB-permeable EGFR inhibitor that is active against multiple EGFR mutations (E19del, L858R, and T790M), including C797S.

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

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.

Rivastigmine (Exelon) is a Cholinesterase Inhibitor, used for therapy of Alzheimer disease.

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.

4-Hydroxyantipyrine is formed during oxidative deamination of aminopyrine.

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.

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) with an IC50 of 8.9 nM. It effectively inhibits and disaggregates self-induced Aβ aggregation, exhibits significant antioxidant activity, and demonstrates substantial penetration through the blood-brain barrier (BBB), holding 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.

Repinotan (BAY x 3702 free base) is an orally active, selective 5-HT1A receptor agonist that crosses the blood-brain barrier (BBB), exhibits neuroprotective activity, counteracts morphine-induced depression of ventilation in anesthetized rats, and may 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.

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].

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

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.

A 1070722 is a potent and selective GSK-3 inhibitor, exhibiting high affinity for both GSK-3α (Ki = 0.6 nM) and GSK-3β (Ki = 0.6 nM). It can penetrate the blood-brain barrier (BBB) and accumulate in brain regions, indicating potential use as a PET radiotracer for quantifying GSK-3 in the brain.

high affinity agonist of the translocator protein

P7C3-A20, a derivative of P7C3, exhibits both proneurogenic and neuroprotective activities (brackets).

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

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

FAUC 213 is a selective full antagonist of the dopamine D4 receptor.

pCPA methyl ester hydrochloride (4-Chloro-DL-phenylalanine methyl ester hydrochloride) is an inhibitor of tryptophan hydroxylase inhibitor and 5-HT synthesis. pCPA methyl ester hydrochloride is permeable across the blood-brain barrier and reduces 5-HT central availability.

LY2886721, a BACE inhibitor, is used for the therapy of Alzheimer's Disease.

Aleplasinin (PAZ 417) is a selective and orally active inhibitor of Plasminogen activator inhibitor-1(PAI-1) and a key negative regulator of the fibrinolytic system. Aleplasinin can be used in Alzheimer's disease studies.

ARN-21934 is a potent, highly selective, blood-brain barrier (BBB) penetrant inhibitor for human topoisomerase II α over β. It inhibits DNA relaxation with an IC50 of 2 μM, compared to 120 μM for Etoposide. ARN-21934 exhibits favorable in vivo pharmacokinetic properties and shows promise in anticancer research, displaying affinity for topoIIα with an IC50 of 2 μM and for topoIIβ with an IC50 of 120 μM. It demonstrates activity against human cancer cell lines including melanoma (A375: 12.6 μM, G-361: 8.1 μM), breast (MCF7: 15.8 μM), endometrial (HeLa: 38.2 μM), lung (A549: 17.1 μM), and prostate (DU145: 11.5 μM) cancer cells. Following a single intraperitoneal injection of 10 mg kg, ARN-21934 achieves a peak plasma concentration of 0.68 μg mL in 15 minutes, with a half-life of 149 minutes, and remains detectable in plasma and the brain for up to 360 minutes. [1] Jose Antonio Ortega, et al. Novel, Potent, and Druglike Tetrahydroquinazoline Inhibitor That Is Highly Selective for Human Topoisomerase II α over β. J Med Chem. 2020 Nov 12;63(21):12873-12886.

Tirabrutinib (GS-4059) (ONO-4059) is an orally active Bruton’s Tyrosine Kinase (Btk) inhibitor (can cross the blood-brain barrier (BBB)), with an IC50 of 6.8 nM. Tirabrutinib irreversibly and covalently binds to Btk and inhibits aberrant B cell receptor signaling. Tirabrutinib can be used in studies of autoimmune diseases and hematological malignancies.

CRANAD-28 is a blood-brain barrier (BBB) penetrating two-photon imaging probe capable of visualizing amyloid plaques and labeling plaques and cerebral amyloid angiopathy.

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

Tubulin inhibitor 41 (Compd D19) is a promising lead compound for glioblastoma treatment, known for its ability to penetrate the blood-brain barrier (BBB). It functions as a tubulin inhibitor, inducing G2 M phase arrest, leading to cell apoptosis, and inhibiting the migration of U87 cells [1].

Compound 11n (hMAO-B-IN-7) is a potent inhibitor of human monoamine oxidase-B (hMAO-B) that can cross the blood-brain barrier (BBB). It demonstrates an IC 50 value of 0.79±0.05 μM and is useful in research related to Alzheimer's disease (AD) and Parkinson's disease (PD) [1].

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 effectively reduces excessive AChE and BuChE levels associated with Alzheimer's disease (AD) and holds potential for anti-Alzheimer's research [1].

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

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.

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

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].

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.

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].

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 with an IC50 value of 126 nM and can cross the blood-brain barrier (BBB). The compound, labeled with [18F], shows promising potential for preclinical evaluation in mice and nonhuman primates (NHP) as a tool for investigating brain ABHD6 activity [1].

NMDA receptor antagonist 4 (IIc) is an uncompetitive, voltage-dependent, orally active NMDAR blocker with an IC50 of 1.93 μM. It shows 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.

Rabies Virus Glycoprotein (TFA), a 29-amino acid-derived cell-penetrating peptide from the Rabies Virus Glycoprotein, can cross the blood-brain barrier (BBB) and enter brain cells.

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

(+)-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.

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).

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].

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.