lonodelestat   Click here for help

GtoPdb Ligand ID: 11275

Synonyms: cyclo[Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-D-Pro-Pro-Nle(Bu)-Glu-Thr] | POL-6014 | POL6014
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Lonodelestat is a modified cyclic peptide (macrolide) that acts as a selective inhibitor of human neutrophil elastase (hNE). It is being developed by Santhera Pharmaceuticals, under license from its originator Polyphor. In April 2020 Santhera announced a COVID-19 collaboration, in which non-clinical research will be conducted by Cold Spring Harbor Laboratory (CSHL) to further validate hNE as a target and assess lonodelestat as a potential agent for treating COVID-19-related acute respiratory distress syndrome (ARDS).
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 33
Hydrogen bond donors 15
Rotatable bonds 23
Topological polar surface area 510.24
Molecular weight 1477.82
XLogP 4.88
No. Lipinski's rules broken 3
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 NCCCC[C@@H]1NC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]2N(C(=O)[C@@H]3N(C(=O)[C@@H](NC1=O)Cc1ccc(cc1)O)CCC3)CCC2)CCCCCCCC)CCC(=O)O)[C@H](O)C)[C@H](CC)C
Isomeric SMILES NCCCC[C@@H]1NC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]2N(C(=O)[C@@H]3N(C(=O)[C@@H](NC1=O)Cc1ccc(cc1)O)CCC3)CCC2)CCCCCCCC)CCC(=O)O)[C@H](O)C)[C@H](CC)C
InChI InChI=1S/C71H111N15O19/c1-6-8-9-10-11-12-19-46-60(94)76-48(30-32-56(91)92)63(97)82-58(42(5)88)67(101)74-41(4)59(93)80-50(39-87)64(98)81-57(40(3)7-2)71(105)86-37-18-24-54(86)70(104)84-35-16-22-52(84)66(100)78-47(29-31-55(73)90)62(96)75-45(20-13-14-33-72)61(95)79-49(38-43-25-27-44(89)28-26-43)68(102)85-36-17-23-53(85)69(103)83-34-15-21-51(83)65(99)77-46/h25-28,40-42,45-54,57-58,87-89H,6-24,29-39,72H2,1-5H3,(H2,73,90)(H,74,101)(H,75,96)(H,76,94)(H,77,99)(H,78,100)(H,79,95)(H,80,93)(H,81,98)(H,82,97)(H,91,92)/t40-,41-,42+,45-,46-,47-,48-,49-,50-,51-,52-,53+,54-,57-,58-/m0/s1
InChI Key JMWYNUHGKFJVIB-QGFXQWJDSA-N
No information available.
Summary of Clinical Use Click here for help
Lonodelestat's clinical efficacy in cystic fibrosis (CF) is under investigation. Results from a study of orally inhaled (nebulised) lonodelestat in healthy volunteers and subjects with CF were published in early 2020 [1].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03748199 Clinical Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of POL6014 in Patients With CF Phase 1/Phase 2 Interventional Santhera Pharmaceuticals