Linsitinib

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

Identification

Generic Name
Linsitinib
DrugBank Accession Number
DB06075
Background

An orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. IGF-1R inhibitor OSI-906 selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 421.504
Monoisotopic: 421.190260381
Chemical Formula
C26H23N5O
Synonyms
  • Linsitinib
External IDs
  • ASP-7487
  • OSI-906
  • OSI-906AA

Pharmacology

Indication

Investigated for use/treatment in cancer/tumors (unspecified) and solid tumors.

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

In laboratory studies of 28 human tumor cell lines, OSI-906 reduced growth of 15 cell lines representative of colorectal, lung, breast, pancreatic, and pediatric tumors and in mouse models. OSI-906 was particularly effective against tumors that are highly IGF-dependent such as colorectal cancers. According to the researchers, OSI-906 not only slowed tumor growth in mice, but decreased the size of some pre-existing tumors.

Mechanism of action

IGF-1R stimulates proliferation, enables onogenic transformation, and suppresses apoptosis. Inhibitors of IGF-1R are expected to have broad utility in oncology since the over-expression of IGF-1R and/or its ligands or the down-regulation of ligand binding proteins occurs in numerous human malignancies including lung, colon, breast, prostate, brain and skin cancers. In addition, signaling through the IGF system has been implicated in protecting tumor cells from apoptosis induced by anti-cancer treatments such as cytotoxic agents and EGFR inhibitors.

TargetActionsOrganism
UInsulin-like growth factor 1 receptor
inhibitor
Humans
UInsulin receptor
inhibitor
Humans
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
Not Available
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
15A52GPT8T
CAS number
867160-71-2
InChI Key
PKCDDUHJAFVJJB-VLZXCDOPSA-N
InChI
InChI=1S/C26H23N5O/c1-26(32)14-19(15-26)25-30-22(23-24(27)28-11-12-31(23)25)18-8-7-17-9-10-20(29-21(17)13-18)16-5-3-2-4-6-16/h2-13,19,32H,14-15H2,1H3,(H2,27,28)/t19-,26+
IUPAC Name
(1s,3r)-3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol
SMILES
C[C@@]1(O)C[C@@H](C1)C1=NC(=C2N1C=CN=C2N)C1=CC=C2C=CC(=NC2=C1)C1=CC=CC=C1

References

General References
Not Available
BindingDB
50315887
ChEMBL
CHEMBL1091644
ZINC
ZINC000100071817
Wikipedia
Linsitinib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentAdrenocortical Carcinoma1
2CompletedTreatmentAdenocarcinoma of the Prostate / Hormone Resistant Prostate Cancer / Prostate Cancer - Recurrent / Stage IV Prostate Cancer1
2CompletedTreatmentCarney Complex / Chondrosarcomas / Gastrointestinal Stromal Tumor (GIST) / Paragangliomas1
2CompletedTreatmentNon-Small Cell Lung Cancer (NSCLC) With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy1
2CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentRecurrent Small Cell Lung Carcinoma1
2CompletedTreatmentRefractory Ewing Sarcoma / Relapsed Ewing Sarcoma1
2CompletedTreatmentSolid Tumors, Advanced Solid Tumors1
2TerminatedTreatmentAdvanced Hepatocellular Carcinoma (HCC)1
2TerminatedTreatmentHormone-sensitive Metastatic Breast Cancer1

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
PropertyValueSource
Water Solubility0.0027 mg/mLALOGPS
logP4.32ALOGPS
logP3.42ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)15.23ChemAxon
pKa (Strongest Basic)5.66ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area89.33 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity125.39 m3·mol-1ChemAxon
Polarizability48.04 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involv...
Gene Name
IGF1R
Uniprot ID
P08069
Uniprot Name
Insulin-like growth factor 1 receptor
Molecular Weight
154791.73 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (...
Gene Name
INSR
Uniprot ID
P06213
Uniprot Name
Insulin receptor
Molecular Weight
156331.465 Da
References
  1. Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O'Connor M, Pirritt C, Sun Y, Yao Y, Arnold LD, Gibson NW, Ji QS: Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009 Sep;1(6):1153-71. doi: 10.4155/fmc.09.89. [Article]
  2. Jones RL, Kim ES, Nava-Parada P, Alam S, Johnson FM, Stephens AW, Simantov R, Poondru S, Gedrich R, Lippman SM, Kaye SB, Carden CP: Phase I study of intermittent oral dosing of the insulin-like growth factor-1 and insulin receptors inhibitor OSI-906 in patients with advanced solid tumors. Clin Cancer Res. 2015 Feb 15;21(4):693-700. doi: 10.1158/1078-0432.CCR-14-0265. Epub 2014 Sep 10. [Article]
  3. Ji QS, Mulvihill MJ, Rosenfeld-Franklin M, Cooke A, Feng L, Mak G, O'Connor M, Yao Y, Pirritt C, Buck E, Eyzaguirre A, Arnold LD, Gibson NW, Pachter JA: A novel, potent, and selective insulin-like growth factor-I receptor kinase inhibitor blocks insulin-like growth factor-I receptor signaling in vitro and inhibits insulin-like growth factor-I receptor dependent tumor growth in vivo. Mol Cancer Ther. 2007 Aug;6(8):2158-67. doi: 10.1158/1535-7163.MCT-07-0070. Epub 2007 Aug 1. [Article]

Drug created on November 18, 2007 18:29 / Updated on March 13, 2021 16:57