Identification

Generic Name
XL784
DrugBank Accession Number
DB04991
Background

XL784 is a potent inhibitor of the ADAM-10 metalloprotease enzyme, a target of significant interest because of its important role in blood vessel formation and cell proliferation. XL784 was specifically optimized to be MMP-1 sparing, thus potentially enhancing its safety profile and enabling higher dosing compared with other previously studied metalloprotease inhibitors. Results of single dose Phase I clinical trials of XL784 administered orally to 96 healthy volunteers have demonstrated that XL784 has attractive safety and pharmacokinetic profiles. It is being developed by Exelixis, Inc.

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available

Pharmacology

Indication

For treatment in patients with diabetes who have clinically significant proteinuria.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

XL784 is a potent inhibitor of the ADAM-10 metalloprotease (MP) enzyme, a target of significant interest because of its important role in blood vessel formation and cell proliferation. XL784 was specifically optimized to spare matrix metalloprotease 1 (MMP1), thus potentially significantly enhancing its safety profile and enabling higher dosing in comparison to other MMP inhibitors. Data from a Phase 1 clinical trial of orally administered XL784 in 70 healthy volunteers showed single doses of the compound to be free of side effects and to have an attractive pharmacokinetic profile. XL784 has been reformulated for chronic administration and has demonstrated dose-proportional absorption, was orally bioavailable and was well tolerated.

Mechanism of action

XL784 is a potent small molecule inhibitor of the ADAM-10 metalloprotease enzyme, which plays a role in blood vessel formation and cell proliferation that can cause renal fibrosis and impairment.

TargetActionsOrganism
UDisintegrin and metalloproteinase domain-containing protein 10Not AvailableHumans
Absorption

Orally bioavailable

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Approximately 8 hours

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
Not Available
Classification
Not classified
Affected organisms
  • Humans and other mammals

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
Not Available
PubChem Substance
347909879

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAlbuminuria / Diabetic Nephropathy1

Pharmacoeconomics

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

Properties

State
Solid
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
Zinc ion binding
Specific Function
Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsi...
Gene Name
ADAM10
Uniprot ID
O14672
Uniprot Name
Disintegrin and metalloproteinase domain-containing protein 10
Molecular Weight
84141.515 Da

Drug created at October 21, 2007 22:23 / Updated at June 12, 2020 16:52