Tau Protein Inhibitor

Lonafarnib (Sch66336) is an orally active, blood-brain barrier penetrant farnesyltransferase (FPTase) inhibitor. Lonafarnib increases the phosphorylation levels of Akt, CaMKII and CREB, upregulates BDNF expression in the hippocampus, elevates the content of α7nAChR on cell membranes, and blocks the isoprenylation of H-Ras. Lonafarnib repairs synapses and reverses spatial memory deficits in Aβ1-42 model mice. Lonafarnib inhibits RSV fusion and replication, and alleviates virus-induced lung injury. Lonafarnib activates the lysosomal and autophagic pathways, and reduces the phosphorylation and aggregation of tau. Lonafarnib acts synergistically with Sorafenib (HY-10201) to promote apoptosis, and inhibits the proliferation and invasion of melanoma cells. Lonafarnib inhibits the farnesylation of progerin, repairs nuclear membrane defects, and activates the cGAS-STING-STAT1 signaling pathway. Lonafarnib can be used in research related to diseases including Alzheimer's disease, viral infections, melanoma, and progeria.

Anandamide is an endocannabinoid. Anandamide modulates both neuronal and immune functions through two protein-coupled cannabinoid receptors (CB1 and CB2). Anandamide can activate numerous other receptors like PPARS, TRPV1, and GPR18/GPR55. Anandamide also has potential anti-fungal and anti-inflammatory activities. Anandamide can be used for the research of Alzheimer’s disease (AD) and ulcerative colitis.

Surfen dihydrochloride is a potent heparan sulfate antagonist. Surfen inhibits FGF2 binding and signal transduction. Surfen binds to glycosaminoglycans and reduces tau hyperphosphorylation. Surfen dihydrochloride inhibits the activity of recombinant uronyl 2-O-sulfotransferase with an IC₅₀ of approximately 2 μM. Surfen dihydrochloride inhibits HSV-1 viral infection. Surfen dihydrochloride inhibits neural differentiation, delays remyelination, and alleviates EAE.

Bepranemab is a humanized IgG4 monoclonal antibody that binds to the central region of tau protein. Bepranemab inhibits the seeding, aggregation of pathological tau protein and the spread of tau pathology to distal brain regions. Bepranemab is applicable to research related to Alzheimer's disease.

Schisantherin B (Gomisin-B) is a lignan compound and one of the active components of Schisandra chinensis. Schisantherin B activates the PI3K/AKT signaling pathway, restores the activity of GSK3β, and reduces the hyperphosphorylation of tau protein in hippocampal and cerebral cortical tissues. Schisantherin B upregulates the level of GLT-1, decreases the expression of pro-inflammatory cytokines TNF-α/IL-1β/IL-6, upregulates the expression of IL-10, and inhibits cell apoptosis. Schisantherin B is applicable to the research of spinal cord injury, Alzheimer's disease and depression.

Ganglioside GQ1b (​Tetrasialoganglioside GQ1b) (bovine) sodium is a central and peripheral nervous system ganglioside and an immunostimulator. Ganglioside GQ1b (bovine) sodium modulates NMDA receptor signaling via ERK1/2, PKA, CREB, NR2A, NR2B, and GSK3β, and increases BDNF expression. Ganglioside GQ1b (bovine) sodium reduces Aβ pathology, tau phosphorylation, and APP levels. Ganglioside GQ1b (bovine) sodium can be used for the research of Alzheimer’s disease.

Leucomethylene blue (TRx0237) mesylate, an orally active second-generation tau protein aggregation inhibitor (K_i of 0.12 μM), could be used for the study of Alzheimer's Disease. Leucomethylene blue mesylate is a common reduced form of Methylene Blue, Methylene Blue is a member of the thiazine class of dyes.

Tomaralimab (OPN-305) is a humanized anti-TLR2 IgG4 monoclonal antibody. Tomaralimab inhibits TLR2, MyD88, NLRP3, and reduces pro-inflammatory cytokine (IL-1β, IL-6, IL-8) production. Tomaralimab reduces tau pathology. Tomaralimab improves cognition, atopic dermatitis. Tomaralimab has anticancer effects on pancreatic ductal adenocarcinoma. Tomaralimab is being studied in myelodysplastic syndrome (MDS), atopic dermatitis, pancreatic ductal adenocarcinoma, Alzheimer's disease, and myocardial ischemia/reperfusion injury.

Levistolide A is an apoptosis inducer and a PEDV virus inhibitor. Levistolide A can induce apoptosis in colon cancer cells and suppress the replication of porcine epidemic diarrhea virus (PEDV) by promoting ROS generation. Levistolide A activates peroxisome proliferator-activated receptor γ (PPARγ) in N2a/APP695swe cells and reduces excessive phosphorylation of tau through the GSK3α/β pathway, improving symptoms in Alzheimer’s mice. Levistolide A improves kidney damage in 5/6 nephrectomy (Nx) mice by inhibiting the RAS,TGF-β1/Smad, and MAPK pathways.

CS640 (Compound 19) is a chemical probe and a calmodulin-dependent kinase inhibitor. CS640 inhibits CaMK1D, CaMK1B, CaMK1A, CaMK1G, MEK5, RIPK4, mLK3 and PIP5K1, with IC₅₀ values of 8, 3, 1, 1, 25 nM, 5.69, 2.75 and 11.2 μM, respectively. CS640 blocks Aβ-induced hyperphosphorylation of tau protein at the Thr181 site, but fails to protect primary mouse cortical neurons from Aβ-induced toxic damage. CS640 is applicable to research related to Alzheimer's disease.

TTBK1-IN-1 is a potent, selective and brain-penetrant tau tubulin kinase 1 (TTBK1) inhibitor with an IC₅₀ of 2.7 nM. TTBK1-IN-1 can be used for the research of alzheimer’s disease and related tauopathies. TTBK1-IN-1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Semorinemab (RG 6100) is an anti-Tau humanized IgG4 monoclonal antibody, targets the N-terminal portion of the Tau protein (amino acid residues 6-23). Semorinemab binds with human Tau with a K_d value of 3.8 nM. Semorinemab can be used for the research of Alzheimer's Disease.

Etalanetug (E2814) is a humanized high-affinity IgG1 antibody that targets tau protein and can cross the blood-brain barrier. Etalanetug inhibits the spread of pathological tau protein through high-affinity binding to the microtubule-binding region (MTBR). Etalanetug can be used in research related to Alzheimer's disease.

Diranersen (IONIS-MAPTRx) is an antisense oligonucleotide that targets the human MAPT gene to inhibit the production of tau protein. Diranersen can be used in research related to Alzheimer's disease and tauopathies.

Posdinemab (JNJ-63733657) is a humanized IgG1/κ monoclonal antibody that selectively targets phosphorylated tau (pT217). Posdinemab specifically binds to the pT217+tau epitope rich in the proline domain, blocks tau protein aggregation and seed propagation, and promotes the clearance of extracellular tau species. Posdinemab reduces the levels of free and total p217+tau in cerebrospinal fluid, thereby inhibiting the pathological propagation of tau protein and the formation of neurofibrillary tangles. Posdinemab can be used for the study of progressive supranuclear palsy syndrome and Alzheimer's disease (AD), especially for prodromal or mild AD disease.

Zagotenemab (LY3303560) is a humanized anti-tau antibody that selectively binds and neutralises tau deposits in the brain. Zagotenemab can be used in Alzheimer's disease research.

Verbenalin is an orally active terpenoid glycoside that can be extracted from the medicinal plant Verbena officinalis. Verbenalin has anti-inflammatory, antiviral, and neuroprotective effects. Verbenalin has a strong binding affinity to the nsp-12 protein of the SARS-CoV-2 virus. Verbenalin can be used in the research of inflammatory and nervous system diseases such as hepatitis and Alzheimer's disease.

Diranersen (IONIS-MAPTRx) sodium is an antisense oligonucleotide that targets the human MAPT gene to inhibit the production of tau protein. Diranersen sodium can be used in research related to Alzheimer's disease and tauopathies.

REM127 is an orally active, blood-brain barrier-penetrant septin 6/7 molecular glue degrader. REM127 binds to SEPT6 with high affinity and promotes the assembly of SEPT2/6/7 cortical filaments, thereby normalizing cytoplasmic calcium levels, cerebrospinal fluid hyperphosphorylated tau protein levels, synaptic function and cognitive function. REM127 can be used in research related to Alzheimer's disease.

Tilavonemab (ABBV-8E12) is a humanized anti-tau monoclonal antibody that binds to amino acids 25-30 near the N-terminus of the tau protein. Tilavonemab can block the ability of human and mouse neurons to uptake tau aggregates. Tilavonemab can be used for research on Alzheimer’s disease and other tauopathies.