sebetralstat   Click here for help

GtoPdb Ligand ID: 11947

Synonyms: compound 14w [PMID: 36251573] | KVD-900 | KVD900
Compound class: Synthetic organic
Comment: KVD900 is an oral plasma kallikrein (KLKB1) inhibitor that is being developed by KalVista Pharmaceuticals as a therapeutic option that is intended for use early upon the onset of hereditary angioedema (HAE) attacks [2]. Its structure was revealed during the 'first disclosure' session at the ACS Spring 2022 meeting. Formal disclosure was in J. Med. Chem. in October 2022 [1], and this associated KVD900 with the INN sebetralstat.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 11
Topological polar surface area 100.27
Molecular weight 491.52
XLogP 2.86
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES COCc1nn(cc1C(=O)NCc1nccc(c1F)OC)Cc1ccc(cc1)Cn1ccccc1=O
Isomeric SMILES COCc1nn(cc1C(=O)NCc1nccc(c1F)OC)Cc1ccc(cc1)Cn1ccccc1=O
InChI InChI=1S/C26H26FN5O4/c1-35-17-22-20(26(34)29-13-21-25(27)23(36-2)10-11-28-21)16-32(30-22)15-19-8-6-18(7-9-19)14-31-12-4-3-5-24(31)33/h3-12,16H,13-15,17H2,1-2H3,(H,29,34)
InChI Key KGMPDQIYDKKXRD-UHFFFAOYSA-N
References
1. Davie RL, Edwards HJ, Evans DM, Hodgson ST, Stocks MJ, Smith AJ, Rushbrooke LJ, Pethen SJ, Roe MB, Clark DE et al.. (2022)
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.
J Med Chem, 65 (20): 13629-13644. [PMID:36251573]
2. Duckworth EJ, Murugesan N, Li L, Rushbrooke LJ, Lee DK, De Donatis GM, Maetzel A, Yea CM, Hampton SL, Feener EP. (2022)
Pharmacological suppression of the kallikrein kinin system with KVD900: An orally available plasma kallikrein inhibitor for the on-demand treatment of hereditary angioedema.
Clin Exp Allergy, 52 (9): 1059-1070. [PMID:35278245]
3. Maetzel A, Smith MD, Duckworth EJ, Hampton SL, De Donatis GM, Murugesan N, Rushbrooke LJ, Li L, Francombe D, Feener EP et al.. (2022)
KVD900, an oral on-demand treatment for hereditary angioedema: Phase 1 study results.
J Allergy Clin Immunol, 149 (6): 2034-2042. [PMID:35086692]