LY 2157299

Base Information

• Chemical Name: LY 2157299
• CAS No.: 700874-72-2
• Molecular Formula: C22H19N5O
• Molecular Weight: 369.42
• Hs Code.: 29334900
• Mol file: 700874-72-2.mol

Synonyms:4-[2-(6-Methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide;LY 2157299;4-[2-(6-Methylpyridin-2-yl)-4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide;

Chemical Property of LY 2157299

Chemical Property:

• Boiling Point: 619.004 °C at 760 mmHg
• PKA: 15.27±0.30(Predicted)
• Flash Point: 328.162 °C
• PSA: 86.69000
• Density: 1.409 g/cm³
• LogP: 4.21410
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to 25 mg/ml)

Purity/Quality:

98%,99%, ^*data from raw suppliers

LY2157299 ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 25
• Safety Statements: 45

MSDS Files:

SDS file from LookChem

Useful:

• Description: Galunisertib (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.
• Uses: LY2157299 is a TGF-β type I receptor kinase inhibitor. LY2157299 has been used to inhance chemotherapy action against triple negative breast cancer (TNBC). LY2157299 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]

Technology Process of LY 2157299

There total 3 articles about LY 2157299 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 89.0%

4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carbonitrile (924898-13-5) → LY2157299 (700874-72-2)

Guidance literature:

With water; sodium hydroxide; In 1-methyl-pyrrolidin-2-one; at 73 - 77 ℃; for 4h; Temperature; Kinetics; Inert atmosphere; Large scale;

DOI:10.1021/op4003054

Reference yield: 63.8%

4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoline-6-carboxylic acid methyl ester (476475-44-2) → LY2157299 (700874-72-2)

Guidance literature:

With ammonia; In methanol; at 90 ℃; for 66h; under 4137.29 Torr;

Reference yield:

4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carbonitrile (924898-13-5) → LY2157299 (700874-72-2) + C44H36N10O (1554203-09-6)

Guidance literature:

With water; sodium hydroxide; In 1-methyl-pyrrolidin-2-one; at 75 ℃; for 6h; Inert atmosphere;

DOI:10.1021/op4003054

upstream raw materials:

4-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoline-6-carboxylic acid methyl ester

4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carbonitrile

Refernces

• 1、 -. "QUINOLINYL-PYRROLOPYRAZOLES". Page 10. . Retrieved 2010/02/07.