Osi-906
Grundinformationen
- CAS
867160-71-2- Standard-SMILES
CC1(O)CC(c2nc(-c3ccc4ccc(-c5ccccc5)nc4c3)c3c(N)nccn23)C1- InChIKey
PKCDDUHJAFVJJB-VLZXCDOPSA-N- Summenformel
- C26H23N5O
- Durchschnittliche Molmasse
- 421,5 g/mol
- Monoisotopische Masse
- 421,19026037
Überblick
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.
Namen und Bezeichner
- Bevorzugter Name
- Osi-906
- IUPAC
- 3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol
- Englischer Name
- Linsitinib
- Summenformel
- C26H23N5O
- Molmasse
- 421.49
Namen und Synonyme
OSI-906OSI 906RefChem:928309Linsitinib867160-71-2Linsitinib(OSI-906)OSI906OSI-906 (Linsitinib)ASP-7487OSI-906AAKinome_3532Linsitinib (OSI-906)
Weitere Namen anzeigen
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
Datenbank-Bezeichner
- CAS
867160-71-2、867160-72-3- PubChem CID
- 11640390
- DTXSID
DTXSID401007055- ChEMBL
CHEMBL1996234- ChEBI
CHEBI:91402- UNII
- 15A52GPT8T
- Nikkaji
- J3.288.961A
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 4,2
- Polarare Oberfläche (TPSA)
- 89,3 Ų
- H-Brücken-Donoren
- 2
- H-Brücken-Akzeptoren
- 5
- Frei drehbare Bindungen
- 3
- Schwere Atome
- 32
- Formalladung
- 0
- Komplexität
- 663
Experimentelle und physikochemische Eigenschaften
DrugsPharmaceuticals -> Listed in ZINC15
Physikochemische Eigenschaften
- Schmelzpunkt
- 175 °C · >175°C (dec.)
- Dichte
- 1.39 · 1.39
- storage temp.
- -20 °C · -20°C
- Löslichkeit
- Soluble in DMSO (up to 30 mg/ml)
- pka
- 14.84 · 14.84±0.40(Predicted)
- Aggregatzustand
- solid
- Farbe
- Yellow
- Stabilität
- 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
Chemie und Industrie
Pharmakologische Informationen
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.
Anwendungen
BeschreibungThe 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.
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