Linsitinib
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
- 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.
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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.
Target Actions Organism UInsulin receptor inhibitorHumans UInsulin-like growth factor 1 receptor inhibitorHumans - 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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
- External Links
- BindingDB
- 50315887
- ChEMBL
- CHEMBL1091644
- ZINC
- ZINC000100071817
- Wikipedia
- Linsitinib
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Adrenocortical Carcinoma 1 2 Completed Treatment Adenocarcinoma of Prostate / Hormone Resistant Prostate Cancer / Recurrent Prostate Cancer / Stage IV Prostate Cancer 1 2 Completed Treatment Advanced Solid Tumors 1 2 Completed Treatment Carney Complex / Chondrosarcomas / Gastrointestinal Stromal Tumor (GIST) / Paragangliomas 1 2 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 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
Property Value Source Water Solubility 0.0027 mg/mL ALOGPS logP 4.32 ALOGPS logP 3.42 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 15.23 Chemaxon pKa (Strongest Basic) 5.66 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 89.33 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 125.39 m3·mol-1 Chemaxon Polarizability 48.04 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-683bfec929fdeb30e72f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-32c8260db6aa48c9f605 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0uk9-0000900000-eb10ce948282865f8be2 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-1004900000-3e4539f6a1d7298144f5 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0009100000-9453cbe584ea3e9f4490 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01w1-2049100000-8f2ef252b6b5f982f6d8 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- 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
- 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]
- 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]
- 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]
- 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
Drug created at November 18, 2007 18:29 / Updated at March 13, 2021 16:57