microtubule associated protein tau   Click here for help

GtoPdb Ligand ID: 9275

Compound class: Endogenous peptide in human, mouse or rat
Comment: The MAPT gene transcript undergoes complex, regulated alternative splicing. Different splice variants are expressed in different neurons and at different stages of neuronal maturation. The 757 amino acid isoform 1 contains three tau/MAP repeats which mediate tau interaction with tubulin (isoforms with four tau/MAP repeats are also reported).

MAPT gene polymorphisms are reported to predispose to neurodegenerative diseases including Alzheimer's disease (AD), Pick's disease [3-4,7] and frontotemporal dementia [5-6,11]. These types of conditions are known as tauopathies. The neurofibrillary tangles detected in AD brains are made up of pathologic paired helical filaments composed in large part of a truncated 100-amino-acid fragment of tau protein [10].

So far we have annotated three types of target relationships for tau protein:
1) aggregation antagonists/inhibitors (e.g. leucomethylthioninium)
2) imaging reagents for detection (e.g. flortaucipir (18F))
3) anti-tau monoclonal antibodies (e.g. zagotenemab)

In addition to zagotenemab, other clinical stage mAbs that target tau include gosuranemab (BMS-986168/BIIB092; for progressive supranuclear palsy PSP- development terminated, primary endpoint was not met in Phase 2), semorinemab (RO-7105705; for AD), tilavonemab (ABBV-8E12; for PSP and AD) and bepranemab (UCB0107; originally in development for PSP).
Species: Human
Selectivity at ligand targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
zagotenemab Hs Antibody Binding 9.7 pKd - 1
⤷ pKd 9.7 (Kd 2.2x10-10 M) [1]
Description: Binding affinity for soluble tau aggregate by surface plasmon resonance (SPR).
Other ligands which bind to or alter the activity of this ligand
Key to terms and symbols Click column headers to sort
Ligand Sp. Type Action Value Parameter Concentration range (M) Reference
QC-01-175 Small molecule or natural product Hs None Binding 5.9 pKd - 9
⤷ pKd 5.9 (Kd 1.2x10-6 M) [9]
Description: In vitro binding affinity for wild-type human tau determined using a biolayer interferometry (BLI) assay.
PROTAC T3 Small molecule or natural product Hs None Binding 5.6 pKd -
⤷ pKd 5.6 (Kd 2.78x10-6 M)
flortaucipir (18F) Small molecule or natural product Ligand is labelled Ligand is radioactive Hs None Binding - - - 8
⤷ [8]
leucomethylthioninium Small molecule or natural product Hs Inhibitor Binding - - - 2
⤷ [2]