Osi-906
Basic information
- CAS
867160-71-2- Standard SMILES
CC1(O)CC(c2nc(-c3ccc4ccc(-c5ccccc5)nc4c3)c3c(N)nccn23)C1- InChIKey
PKCDDUHJAFVJJB-VLZXCDOPSA-N- Molecular formula
- C26H23N5O
- Average molar mass
- 421.5 g/mol
- Monoisotopic mass
- 421.19026037
Overview
Linsitinib is an imidazopyrazine that is imidazo[1,5-a]pyrazine substituted by 2-phenylquinolin-7-yl, cis-3-hydroxy-3-methylcyclobutyl, and amino groups at positions 1, 3, and 8, respectively. It is dual inhibitor of the IGF-1 receptor and insulin receptor (IC50 = 35 and 75 nM, respectively) that was previously in clinical development for the treatment of cancer and thyroid eye disease. It has a role as an antineoplastic agent, an antimycobacterial drug, an apoptosis inducer and an insulin-like growth factor receptor 1 antagonist. It is a member of cyclobutanes, a member of benzenes, a member of quinolines, a tertiary alcohol, an aromatic amine and an imidazopyrazine.
Names & identifiers
- Preferred name
- Osi-906
- IUPAC
- 3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol
- English name
- Linsitinib
- Molecular formula
- C26H23N5O
- Molecular weight
- 421.49
Names & synonyms
OSI-906OSI 906RefChem:928309Linsitinib867160-71-2Linsitinib(OSI-906)OSI906OSI-906 (Linsitinib)ASP-7487OSI-906AAKinome_3532Linsitinib (OSI-906)
Show more names
CS-190OSI 906AALinsitinib(OSI906)OSI-906 LinsitinibLinsitinib USP/EP/BPLinsitinib (ASP-7487
3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-olMFCD12912153C26H23N5OLinsitinib (USAN/INN)15A52GPT8TCHEMBL1091644CHEBI:91402HMS3295G15
Database identifiers
- CAS
867160-71-2、867160-72-3- PubChem CID
- 11640390
- DTXSID
DTXSID401007055- ChEMBL
CHEMBL1996234- ChEBI
CHEBI:91402- UNII
- 15A52GPT8T
- Nikkaji
- J3.288.961A
Properties
Computed structural properties
- XLogP
- 4.2
- Topological polar surface area
- 89.3 Ų
- Hydrogen bond donors
- 2
- Hydrogen bond acceptors
- 5
- Rotatable bonds
- 3
- Heavy atoms
- 32
- Formal charge
- 0
- Complexity
- 663
Experimental & physicochemical properties
DrugsPharmaceuticals -> Listed in ZINC15
Physicochemical properties
- Melting point
- 175 °C · >175°C (dec.)
- Density
- 1.39 · 1.39
- storage temp.
- -20 °C · -20°C
- solubility
- Soluble in DMSO (up to 30 mg/ml)
- pka
- 14.84 · 14.84±0.40(Predicted)
- form
- solid
- color
- Yellow
- Stability
- 1 year · Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
- InChIKey
- PKCDDUHJAFVJJB-VLZXCDOPSA-N
- SMILES
- [C@]1(C)(O)C[C@H](C2N3C=CN=C(N)C3=C(C3C=C4C(=CC=3)C=CC(C3=CC=CC=C3)=N4)N=2)C1
- NCI Dictionary of Cancer Terms
- -906 · OSI-906
- FDA UNII
- 15 A52GPT8T · 15A52GPT8T
Safety & regulation
Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.
Safety data
- Signal word
- Warning
- Symbol(GHS)
- GHS07
Chemistry & industry
Pharmacology
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.
Applications
DescriptionLinsitinib (OSI-906) is a selective inhibitor of IGF-1R with IC50 of 35 nM in cell-free assays; modestly potent to InsR with IC50 of 75 nM, and no activity towards Abl, ALK, BTK, EGFR, FGFR1/2, PKA etc. Phase 3.
DescriptionThe binding of insulin-like growth factor 1 (IGF-1) to the IGF-1 receptor (IGF-1R) promotes cell growth while inhibiting apoptotic pathways. Overexpression of IGF-1R is found in certain solid tumors and hematologic neoplasias. However, insulin receptor (InsR) signaling can compensate for IGF-1R inhibition. Linsitinib is a dual inhibitor of IGF-1R and InsR kinases (IC50s = 35 and 75 nM, respectively). It also inhibits InsR-related receptor (IC50 = 75 nM) but is without effect (IC50 > 10 μM) against a large panel of other kinases. Linsitinib inhibits proliferation of a variety of tumor cell lines in vitro and has antitumor efficacy in an IGF-1R-driven xenograft mouse model when administered orally. A rapid, non-invasive method to predict the pharmacodynamic response to linsitinib has been reported.
UsesLinsitinib is a small-molecule dual insulin-like growth factor-1 receptor (IGF-IR) and insulin receptor (IR) kinase inhibitor. IGF-I receptor (IGF-IR) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies and thus Linsitinib may be a useful anticancer agent. Potent IGF-1R inhibitor.
Related reactions
0 records
No reaction records under the current filter.
Compound notes
Loading…