Target Information
| Target General Information | Top | |||||
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| Target ID |
T45593
(Former ID: TTDI01945)
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| Target Name |
Microtubule-associated protein tau (MAPT)
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| Synonyms |
tau; Paired helical filamenttau; Paired helical filament-tau; Neurofibrillary tangle protein; MTBT1; MAPTL
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| Gene Name |
MAPT
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
| 2 | Alzheimer disease [ICD-11: 8A20] | |||||
| 3 | Mild neurocognitive disorder [ICD-11: 6D71] | |||||
| Function |
The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.
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| UniProt ID | ||||||
| Sequence |
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPG
SETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAG HVTQEPESGKVVQEGFLREPGPPGLSHQLMSGMPGAPLLPEGPREATRQPSGTGPEDTEG GRHAPELLKHQLLGDLHQEGPPLKGAGGKERPGSKEEVDEDRDVDESSPQDSPPSKASPA QDGRPPQTAAREATSIPGFPAEGAIPLPVDFLSKVSTEIPASEPDGPSVGRAKGQDAPLE FTFHVEITPNVQKEQAHSEEHLGRAAFPGAPGEGPEARGPSLGEDTKEADLPEPSEKQPA AAPRGKPVSRVPQLKARMVSKSKDGTGSDDKKAKTSTRSSAKTLKNRPCLSPKHPTPGSS DPLIQPSSPAVCPEPPSSPKYVSSVTSRTGSSGAKEMKLKGADGKTKIATPRGAAPPGQK GQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREP KKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLD LSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEK LDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDT SPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T93LMN | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 9 Clinical Trial Drugs | + | ||||
| 1 | Davunetide | Drug Info | Phase 3 | Cognitive impairment | [1] | |
| 2 | LMT-X | Drug Info | Phase 3 | Acute myeloid leukaemia | [2] | |
| 3 | TRx0237 | Drug Info | Phase 3 | Alzheimer disease | [3] | |
| 4 | BIIB092 | Drug Info | Phase 2 | Progressive supranuclear palsy | [4] | |
| 5 | PBT-2 | Drug Info | Phase 2 | Alzheimer disease | [5] | |
| 6 | RG6100 | Drug Info | Phase 2 | Alzheimer disease | [6] | |
| 7 | Tau-binding PET tracer | Drug Info | Phase 2 | Alzheimer disease | [7] | |
| 8 | LY3303560 | Drug Info | Phase 1 | Alzheimer disease | [8] | |
| 9 | PTI-80 | Drug Info | Phase 1 | Alzheimer disease | [9] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 6 Modulator drugs | + | ||||
| 1 | Davunetide | Drug Info | [1] | |||
| 2 | PBT-2 | Drug Info | [13], [1] | |||
| 3 | Tau-binding PET tracer | Drug Info | [1] | |||
| 4 | AL-408 | Drug Info | [1] | |||
| 5 | BLV-0703 | Drug Info | [1] | |||
| 6 | NI-105 | Drug Info | [1] | |||
| Inhibitor | [+] 5 Inhibitor drugs | + | ||||
| 1 | LMT-X | Drug Info | [1], [8], [10], [11] | |||
| 2 | TRx0237 | Drug Info | [12] | |||
| 3 | BIIB092 | Drug Info | [11] | |||
| 4 | RG6100 | Drug Info | [11], [8] | |||
| 5 | PTI-80 | Drug Info | [14], [1] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | MAPK signaling pathway | |||||
| 2 | Alzheimer's disease | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | IL2 Signaling Pathway | |||||
| 2 | EGFR1 Signaling Pathway | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | LPA receptor mediated events | |||||
| 2 | Reelin signaling pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Caspase-mediated cleavage of cytoskeletal proteins | |||||
| WikiPathways | [+] 11 WikiPathways | + | ||||
| 1 | Notch Signaling Pathway | |||||
| 2 | IL-2 Signaling Pathway | |||||
| 3 | MAPK Signaling Pathway | |||||
| 4 | Copper homeostasis | |||||
| 5 | Kit receptor signaling pathway | |||||
| 6 | BDNF signaling pathway | |||||
| 7 | Integrated Pancreatic Cancer Pathway | |||||
| 8 | Alzheimers Disease | |||||
| 9 | Regulation of Microtubule Cytoskeleton | |||||
| 10 | Apoptotic execution phase | |||||
| 11 | IL-5 Signaling Pathway | |||||
| References | Top | |||||
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| REF 1 | Microtubules (tau) as an emerging therapeutic target: NAP (davunetide). Curr Pharm Des. 2011;17(31):3413-7. | |||||
| REF 2 | ClinicalTrials.gov (NCT01689246) Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT01689246) Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT03068468) Study of BIIB092 in Participants With Progressive Supranuclear Palsy (PASSPORT). U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01590888) Effect of PBT2 in Patients With Early to Mid Stage Huntington Disease. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT03289143) A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild Alzheimer's Disease. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT02414347) F 18 T807 Tau PET Imaging of Alzheimer's Disease. U.S. National Institutes of Health. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028705) | |||||
| REF 10 | Clinical pipeline report, company report or official report of TauRx. | |||||
| REF 11 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 12 | Mechanisms of Anticholinesterase Interference with Tau Aggregation Inhibitor Activity in a Tau-Transgenic Mouse Model. Curr Alzheimer Res. 2020;17(3):285-296. | |||||
| REF 13 | PBT2 rapidly improves cognition in Alzheimer's Disease: additional phase II analyses. J Alzheimers Dis. 2010;20(2):509-16. | |||||
| REF 14 | Biopharmaceutical Research Companies Are Developing More Than 430 Medicines for Top Chronic Diseases Affecting Older Americans. Pharmaceutical Research and Manufacturers of America report. 2014. | |||||
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