This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Generic Name
PLN-74809
DrugBank Accession Number
DB16515
Background

PLN-74809 is a small-molecule that dually inhibits both αvβ6 and αvβ1 to treat both idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC)2. The compound was granted orphan drug designation by the US FDA in August 2018 for treatment of IPF, and Pliant Therapeutics recently raised $100 million in Series C financing to support further clinical development of this compound5. Phase 2a studies are currently evaluating PLN-74809 safety and efficacy for participants with IPF (NCT04396756)across 10 participating countries4, and for participants with PSC (NCT04480840). In addition, the compound is also currently in Phase 2a trials (NCT04565249) for the treatment of COVID-19 related acute respiratory distress syndrome6.

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available
External IDs
  • PLN-74809

Pharmacology

Indication

Through dual inhibition of integrins αvβ6 and αvβ1, PLN-74809 reduces subsequent activation of TGF-β1, which is actively involved in the growth of fibrotic tissue in lung and bile ducts2. Further studies showed that PLN-74809 inhibited collagen gene expression in PSC and IPF patient tissue3.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
UIntegrin alpha-VNot AvailableHumans
UIntegrin beta-1Not AvailableHumans
UIntegrin beta-6Not AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
Not Available
CAS number
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

References

General References
  1. External Link [Link]
  2. pulmonary fibrosis foundation [Link]
  3. ERS journal [Link]
  4. ERS-Integris IPF [Link]
  5. pulmonary firbrosis news [Link]
  6. biospace [Link]
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2RecruitingTreatmentPrimary Sclerosing Cholangitis (PSC)1
2TerminatedTreatmentAcute Respiratory Distress Syndrome (ARDS) / Coronavirus Disease 2019 (COVID‑19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Voltage-gated calcium channel activity
Specific Function
The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF...
Gene Name
ITGAV
Uniprot ID
P06756
Uniprot Name
Integrin alpha-V
Molecular Weight
116036.855 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Virus receptor activity
Specific Function
Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F...
Gene Name
ITGB1
Uniprot ID
P05556
Uniprot Name
Integrin beta-1
Molecular Weight
88414.575 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Integrin alpha-V:beta-6 (ITGAV:ITGB6) is a receptor for fibronectin and cytotactin (PubMed:17545607, PubMed:17158881). It recognizes the sequence R-G-D in its ligands (PubMed:17545607, PubMed:17158881). Internalisation of integrin alpha-V/beta-6 via clathrin-mediated endocytosis promotes carcinoma cell invasion (PubMed:17545607, PubMed:17158881). ITGAV:ITGB6 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:17158881). Integrin alpha-V:beta-6 (ITGAV:ITGB6) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:15184403, PubMed:22278742, PubMed:28117447).
Specific Function
Integrin binding
Gene Name
ITGB6
Uniprot ID
P18564
Uniprot Name
Integrin beta-6
Molecular Weight
85935.195 Da

Drug created at January 21, 2021 02:02 / Updated at December 17, 2022 02:23