TPT-004   Click here for help

GtoPdb Ligand ID: 12993

Synonyms: compound 32 [Specker et al., 2023] | TPT004
PDB Ligand
Compound class: Synthetic organic
Comment: TPT-004 is a tryptophan hydroxylase (TPH) inhibitor [1]. When bound to the enzyme it occupies a domain across the pterin (cosubstrate) and tryptophan (substrate) binding sites. The compound is highly hydrophilic and is unable to cross the blood-brain barrier. TPT-004 is designed to inhibit TPH1 in the periphery whilst sparing the TPH2 isoform in the brain, to selectively target elevated serotonin levels in the periphery that are associated with pathological conditions (carcinoid syndrome, pulmonary arterial hypertension).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 115.14
Molecular weight 400.46
XLogP 0.52
No. Lipinski's rules broken 0
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Canonical SMILES CCN1C2=C(C(=O)NC1=O)N(CC3COC3)C(=N2)CC4=CN5C=C(C)SC5=N4
Isomeric SMILES CCN1C2=C(N(CC3COC3)C(CC4=CN5C=C(C)SC5=N4)=N2)C(=O)NC1=O
InChI InChI=1S/C18H20N6O3S/c1-3-23-15-14(16(25)21-17(23)26)24(6-11-8-27-9-11)13(20-15)4-12-7-22-5-10(2)28-18(22)19-12/h5,7,11H,3-4,6,8-9H2,1-2H3,(H,21,25,26)
1. Specker E, Wesolowski R, Schutz A, Matthes S, Mallow K, Wasinska-Kalwa M, Winkleer L, Oder A, Alenina N, Pleimes D et al.. (2023)
Structure-Based Design of Xanthine-Imidazopyridines and -Imidazothiazoles as Highly Potent and In Vivo Efficacious Tryptophan Hydroxylase Inhibitors.
J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.3c01454