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).
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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)
Bioactivity Comments
Orally administered TPT-004 reduces peripheral serotonin levels in vivo, and impairs tumour growth in a mouse colon carcinoma model [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
L-Tryptophan hydroxylase 1 Hs Inhibitor Inhibition 8.5 pKd - 1
pKd 8.5 (Kd 3.2x10-9 M) [1]
Description: Binding affinity determined by SPR
L-Tryptophan hydroxylase 2 Hs Inhibitor Inhibition 7.8 pIC50 - 1
pIC50 7.8 (IC50 1.6x10-8 M) [1]
L-Tryptophan hydroxylase 1 Hs Inhibitor Inhibition 7.1 pIC50 - 1
pIC50 7.1 (IC50 7.7x10-8 M) [1]