ArticleJournal of medicinal chemistry2022
Sebetralstat (KVD900): A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema.
Article in Journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- A comprehensive review of small molecule drugs approved by the FDA in 2025: advance and prospect.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Small-Molecule Drugs Approved by the FDA in 2025.Molecules (Basel, Switzerland) · 2026Review
- Nitrogen-containing FDA-approved drugs in 2025: synthesis, significance and therapeutic applications.RSC advances · 2026Review
- Fluorine-containing FDA-approved small-molecule drugs in 2025: significance, synthetic insights, and therapeutic applications.RSC advances · 2026Review
- Halogen-Containing Drugs in 2025: A Record Year for the Therapeutic Use and Synthesis of FDA-Approved Small Molecules.Biomolecules · 2026Review
- Sebetralstat: a paradigm shift in hereditary angioedema management.Annals of medicine and surgery (2012) · 2025Article
- Sebetralstat: First Approval.Drugs · 2025Review
- Advent of oral medications for the treatment of hereditary angioedema.Clinical and translational allergy · 2024Review
- Unveiling therapeutic frontiers: DON/DRP-104 as innovative Plasma kallikrein inhibitors against carcinoma-associated hereditary angioedema shocks - a comprehensive molecular dynamics exploration.Cell biochemistry and biophysics · 2024Article
- Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein.ACS medicinal chemistry letters · 2024Article
- Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond.Frontiers in physiology · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary angioedema (HAE) is a rare genetic disorder in which patients experience sudden onset of swelling in various locations of the body. HAE is associated with uncontrolled plasma kallikrein (PKa) enzyme activity and generation of the potent inflammatory mediator, bradykinin, resulting in episodic attacks of angioedema. Herein, we disclose the discovery and optimization of novel small molecule PKa inhibitors. Starting from molecules containing highly basic P1 groups, which typically bind to an aspartic acid residue (Asp189) in the serine protease S1 pocket, we identified novel P1 binding groups likely to have greater potential for oral-drug-like properties. The optimization of P4 and the central core together with the particularly favorable properties of 3-fluoro-4-methoxypyridine P1 led to the development of sebetralstat, a potent, selective, orally bioavailable PKa inhibitor in phase 3 for on-demand treatment of HAE attacks.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.