Linsitinib

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

Identification

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Name
Linsitinib
Accession Number
DB06075
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
ASP-7487 / OSI-906 / OSI-906AA
Categories
Not Available
UNII
15A52GPT8T
CAS number
867160-71-2
Weight
Average: 421.504
Monoisotopic: 421.190260381
Chemical Formula
C26H23N5O
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

Pharmacology

Indication

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

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 receptorNot 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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
BindingDB
50315887
ChEMBL
CHEMBL1091644
Wikipedia
Linsitinib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherAdvanced Solid Tumors / Pharmacokinetics of 14C-OSI-9061
1CompletedTreatmentAdvanced Solid Tumors3
1CompletedTreatmentMetastatic Colorectal Cancers1
1TerminatedTreatmentColorectal Cancers1
1WithdrawnTreatmentMalignancies / Neoplasms / Tumors1
1, 2CompletedTreatmentCancer of the Ovary / Tumors, Solid1
1, 2WithdrawnTreatmentPancreatic Cancer, Metastatic1
1, 2WithdrawnTreatmentRecurrent Skin Cancer / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Squamous Cell Carcinoma of the Skin / Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity1
2CompletedTreatmentAdenocarcinoma of the Prostate / Hormone-Resistant Prostate Cancer / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
2CompletedTreatmentAdvanced Solid Tumors1
2CompletedTreatmentCarney Complex / Chondrosarcomas / Gastrointestinal Stromal Tumors / Paraganglioma1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentNon-Small Cell Lung Cancer (NSCLC) With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy1
2CompletedTreatmentRecurrent Small Cell Lung Carcinoma1
2CompletedTreatmentRefractory Ewing Sarcoma / Relapsed Ewing Sarcoma1
2TerminatedTreatmentAdvanced Hepatocellular Carcinoma (HCC)1
2TerminatedTreatmentHormone-sensitive Metastatic Breast Cancer1
2TerminatedTreatmentLiver Cancer1
2WithdrawnTreatmentHead and Neck Carcinoma1
3CompletedTreatmentAdrenocortical Carcinoma1

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

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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

Drug created on November 18, 2007 11:29 / Updated on June 04, 2019 06:21