Galunisertib
Grundinformationen
- CAS
700874-72-2- Standard-SMILES
Cc1cccc(-c2nn3c(c2-c2ccnc4ccc(C(N)=O)cc24)CCC3)n1- InChIKey
IVRXNBXKWIJUQB-UHFFFAOYSA-N- Summenformel
- C22H19N5O
- Durchschnittliche Molmasse
- 369,4 g/mol
- Monoisotopische Masse
- 369,15896025
Überblick
LY-2157299 is a pyrrolopyrazole that is 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole which is substituted at positions 2 and 3 by 6-methylpyridin-2-yl and 6-(aminocarbonyl)quinolin-4-yl groups, respectively. A Transforming growth factor-betaRI (TGF-betaRI) kinase inhibitor, it blocks TGF-beta-mediated tumor growth in glioblastoma. It has a role as an antineoplastic agent and a TGFbeta receptor antagonist. It is a member of methylpyridines, a member of quinolines, a monocarboxylic acid amide, a pyrrolopyrazole and an aromatic amide.
Namen und Bezeichner
- Bevorzugter Name
- Galunisertib
- IUPAC
- 4-[2-(6-methyl-2-pyridinyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide
- Englischer Name
- LY 2157299
- Summenformel
- C22H19N5O
- Molmasse
- 369.42
Namen und Synonyme
Galunisertib700874-72-2LY2157299LY 2157299LY-21572994-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carboxamidegalunisertibum3OKH1W5LZE4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamideDTXSID00220362CHEBI:1370646-Quinolinecarboxamide, 4-[5,6-dihydro-2-(6-methyl-2-pyridinyl)-4H-pyrrolo[1,2-b]pyrazol-3-yl]-
Weitere Namen anzeigen
CS-5Galunisertib D6LY2157299, >=98%LY 2157299 USP/EP/BPLY2157299,GalunisertibGalunisertib,LY2157299Galunisertib, 10 mM in DMSO
6-Quinolinecarboxamide, 4-(5,6-dihydro-2-(6-methyl-2-pyridinyl)-4H-pyrrolo(1,2-b)pyrazol-3-yl)-4-(2-(6-METHYLPYRIDIN-2-YL)-5,6-DIHYDRO-4H-PYRROLO(1,2-B)PYRAZOL-3-YL)QUINOLINE-6-CARBOXAMIDE4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo(2,1-e)pyrazol-3-yl)quinoline-6-carboxamide4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[2,1-e]pyrazol-3-yl]quinoline-6-carboxamideRefChem:142227DTXCID00142853Galunisertib (LY2157299)ly2157299(galunisertib)
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 2,4
- Polarare Oberfläche (TPSA)
- 86,7 Ų
- H-Brücken-Donoren
- 1
- H-Brücken-Akzeptoren
- 4
- Frei drehbare Bindungen
- 3
- Schwere Atome
- 28
- Formalladung
- 0
- Komplexität
- 585
Experimentelle und physikochemische Eigenschaften
DrugsPharmaceuticals -> Listed in ZINC15
LogP1.71
Physikochemische Eigenschaften
- Schmelzpunkt
- 241 · 241-242°C
- Siedepunkt
- 619 · 619.0±55.0 °C(Predicted)
- Dichte
- 1.4 · 1.40
- Flammpunkt
- 328.162 ℃ · 328.162℃
- storage temp.
- -20 °C · -20°C
- Löslichkeit
- Soluble in DMSO (up to 25 mg/ml)
- Aggregatzustand
- solid
- pka
- 15.27 · 15.27±0.30(Predicted)
- Farbe
- White
- 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 1 month.
- InChI
- InChI=1S/C22H19N5O/c1-13-4-2-5-18(25-13)21-20(19-6-3-11-27(19)26-21)15-9-10-24-17-8-7-14(22(23)28)12-16(15)17/h2,4-5,7-10,12H,3,6,11H2,1H3,(H2,23,28)
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
GHS-Klassifizierung
GHS Classification
Warning
H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]
P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.
Gefahrenhinweise
Hazard Classes and CategoriesSkin Irrit. 2 (100%)
Sicherheitsdaten
- wgk
- WGK 3
- hs_code
- 29334900
- risk_code
- 25
- hazard_code
- T
- safety_code
- 45
- Speicherklasse
- 11 - Combustible Solids
Chemie und Industrie
Anwendungen
BeschreibungGalunisertib (LY2157299 monohydrate) is a small-molecule inhibitor of TGFβR1 that binds antagonistically to TGFR1 to prevent the intracellular phosphorylation of SMAD2 and SMAD3.Phase I studies have demonstrated that galunisertib had an acceptable tolerability and safety profile in patients with advanced solid tumors.Recently the preclinical studies from Tran et al. demonstrated that galunisertib combined with anti-GD2 antibody Dinutuximab augmented the anti-tumor cytotoxicity of activated NK(aNK) cells which were activated ex vivo with K562.mbIL21 artificial antigen presenting cells.Galunisertib suppressed SMAD2 phosphorylation and restored the expression of DNAX Accessory Molecule-1,NKp30, NKG2D and TNF-related apoptosis-inducing ligand death ligand expression on aNK cells and also significantly enhanced the release of perforin and granzyme A from aNK cells and the direct cytotoxicity and ADCC of aNK cells against neuroblastoma cells in vitro.The combination of galunisertib, aNK cells plus dinutuximab reduced tumor growth and increased survival of mice xenografted with two neuroblastoma cell lines or a patient derived xenograft.In another study,galunisertib was shown to preserve the cytotoxic function of ex vivo expanded, highly activated NK cells and significantly improved eradication of liver metastases of colon cancer in mice treated with adoptive NK cells compared with mice receiving NK cells or TGF beta inhibition alone. Overall these studies demonstrate that the therapeutic efficacy of adoptive NK cell therapy clinically will be markedly enhanced by complementary approaches targeting TGF-beta signaling in vivo.
VerwendenLY2157299 is a small molecule inhibitor of the TGF-β receptor type 1 kinase (IC50 = 56 nM). It has been used to study the role of TGF-β signaling in chemotherapy-induced expansion of cancer stem-like cells in triple negative breast cancer cell lines and xenografts. LY2157299 has also been shown to inhibit the migration and tumor growth of hepatocellular carcinoma cell lines by disrupting Smad-2 phosphorylation.[Cayman Chemical]
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