rodatristat   Click here for help

GtoPdb Ligand ID: 10647

Synonyms: compound 15a [PMID: 28041831] | KAR-5417 | KAR5417
PDB Ligand
Compound class: Synthetic organic
Comment: Rodatristat (KAR5417) inhibits both isoforms of L-Tryptophan hydroxylase (TPH) [2]. The TPH enzymes are responsible for biosynthesis of 5-HT. TPH1 is expressed by intestinal enterochromaffin cells where most peripheral 5-HT is formed, and THP2 is exclusively expressed in the CNS and generates 5-HT in the brain. Rodatristat acts as a serotonin synthesis inhibitor. As rodatristat cannot cross the blood-brain-barrier its activity is restricted to inhibition of peripherally expressed TPH1 and it should not produce the undesirable psychiatric side-effects that are known to result from any reduction in central 5-HT level.
Inhibition of serotonin synthesis is being actively pursued as a mechanistic approach for application to the treatment of the expansive range of diseases that have been associated with a dysfunctional peripheral serotonin system (carcinoid syndrome, gastro-intestinal diseases, fibrotic diseases, NAFLD, atherothrombotic diseases, pulmonary arterial hypertension and some cancers and immune diseases [1,3]).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 113.6
Molecular weight 561.18
XLogP 4.93
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES Nc1nc(cc(n1)N1CCC2(CC1)CN[C@@H](C2)C(=O)O)O[C@@H](C(F)(F)F)c1ccc(cc1c1ccccc1)Cl
Isomeric SMILES Nc1nc(cc(n1)N1CCC2(CC1)CN[C@@H](C2)C(=O)O)O[C@@H](C(F)(F)F)c1ccc(cc1c1ccccc1)Cl
InChI InChI=1S/C27H27ClF3N5O3/c28-17-6-7-18(19(12-17)16-4-2-1-3-5-16)23(27(29,30)31)39-22-13-21(34-25(32)35-22)36-10-8-26(9-11-36)14-20(24(37)38)33-15-26/h1-7,12-13,20,23,33H,8-11,14-15H2,(H,37,38)(H2,32,34,35)/t20-,23+/m0/s1
InChI Key ZNSPHKJFQDEABI-NZQKXSOJSA-N
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Summary of Clinical Use Click here for help
As rodatristat is administered as its prodrug rodatristat ethyl, clinical trials use the research codes of the prodrug (either KAR5585 or RVT-1201). We have curated clinical trial information against both rodatristat and rodatristat ethyl for user benefit. Clinical evauation of rodatristat in patients with pulmonary arterial hypertension (PAH) has advanced to Phase 2.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03924154 A Study of RVT-1201 in Patients With Pulmonary Arterial Hypertension (ELEVATE 1) Phase 2 Interventional Altavant Sciences GmbH