OSI-461

Identification

Generic Name
OSI-461
DrugBank Accession Number
DB05415
Background

OSI-461 is a second-generation molecule belonging to a new class of drugs termed selective apoptotic anti-neoplastic drugs (SAANDs).

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available

Pharmacology

Indication

Investigated for use/treatment in crohn's disease, inflammatory bowel disease, kidney cancer, leukemia (lymphoid), and prostate cancer.

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
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Avoid life-threatening adverse drug events & improve clinical decision support.
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Pharmacodynamics

Not Available

Mechanism of action

OSI-461 is cGMP phosphodiesterase (cGMP-PDEs) inhibitors which is designed to lead to sustained activation of the intracellular signaling protein, Protein Kinase G (PKG), and subsequent stimulation of apoptosis through the c-Jun kinase pathway. Broad spectrum inhibition of cGMP-PDEs have been shown to lead to elevation in cGMP levels and the sustained activation of PKG. This in turn directly phosphorylates MEKK1 leading to activation of the N-terminal c-Jun kinase (JNK-1) pathway, a known pro-apoptotic signaling pathway.

TargetActionsOrganism
UcGMP-specific 3',5'-cyclic phosphodiesteraseNot 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
Adverseeffects
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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. Shimizu M, Suzui M, Deguchi A, Lim JT, Xiao D, Hayes JH, Papadopoulos KP, Weinstein IB: Synergistic effects of acyclic retinoid and OSI-461 on growth inhibition and gene expression in human hepatoma cells. Clin Cancer Res. 2004 Oct 1;10(19):6710-21. [Article]
PubChem Substance
347910126

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentChronic Lymphocytic Leukemia (CLL)1

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

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
Gene Name
PDE5A
Uniprot ID
O76074
Uniprot Name
cGMP-specific 3',5'-cyclic phosphodiesterase
Molecular Weight
99984.14 Da

Drug created on November 18, 2007 18:24 / Updated on June 12, 2020 16:52