berotralstat   Click here for help

GtoPdb Ligand ID: 11347

Synonyms: BCX-7353 | BCX7353 | Orladeyo®
Approved drug PDB Ligand
berotralstat is an approved drug (FDA (2020), EMA (2021))
Compound class: Synthetic organic
Comment: Berotralstat (BCX7353) is an orally bioavailable inhibitor of plasma kallikrein, a proteinase that is encoded by the KLKB1 gene in humans [4]. Plasma kallikrein cleaves Lys-Arg and Arg-Ser bonds in (human) kininogen to release bradykinin. Inhibition of this activity is exploited to reduce bradykinin levels in human disease where abnormally elevated bradykinin induces pathologic vascular permeability and swelling, as seen in patients with hereditary angioedema (HAE; caused by loss of C1 inhibitor SERPING1 expression).
The 'flat' structure of berotralstat with no specified stereochemistry is claimed as compound 52h in Biocryst Pharmaceuticals' patent WO2015134998A1 [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 108.24
Molecular weight 562.21
XLogP 4.86
No. Lipinski's rules broken 0
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Canonical SMILES NCc1cccc(c1)n1nc(cc1C(=O)Nc1cc(ccc1F)[C@@H](c1cccc(c1)C#N)NCC1CC1)C(F)(F)F
Isomeric SMILES NCc1cccc(c1)n1nc(cc1C(=O)Nc1cc(ccc1F)[C@@H](c1cccc(c1)C#N)NCC1CC1)C(F)(F)F
InChI InChI=1S/C30H26F4N6O/c31-24-10-9-22(28(37-17-18-7-8-18)21-5-1-3-19(11-21)15-35)13-25(24)38-29(41)26-14-27(30(32,33)34)39-40(26)23-6-2-4-20(12-23)16-36/h1-6,9-14,18,28,37H,7-8,16-17,36H2,(H,38,41)/t28-/m1/s1
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Summary of Clinical Use Click here for help
Berotralstat (BCX7353) was the first oral, once-daily drug to be approved as a prophylactic to prevent hereditary angioedema (HAE) attacks [5]. EMA orphan designation for HAE was granted in June 2018 [2]. In November 2020 the UK's MHRA authorised early access to berotralstat, to allow HAE patients to receive the drug prior to full regulatory approval. Full EMA approval was issued in April 2021.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03873116 Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan Phase 3 Interventional BioCryst Pharmaceuticals 6
NCT03485911 Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE Phase 3 Interventional BioCryst Pharmaceuticals 6-7
NCT02870972 Efficacy and Safety of BCX7353 to Prevent Angioedema Attacks in Subjects With Hereditary Angioedema Phase 2 Interventional BioCryst Pharmaceuticals 1