700874-72-2 Usage
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
Different sources of media describe the Uses of 700874-72-2 differently. You can refer to the following data:
1. LY2157299 is a TGF-β type I receptor kinase inhibitor. LY2157299 has been used to inhance chemotherapy action against triple negative breast cancer (TNBC).
2. 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]
References
1) Bueno?et al.?(2008),?Semi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299, a new type I receptor TGF-β kinase antagonist, in mice; Eur. J. Cancer?44?142
2) Zhou?et al.?(2011),?Reduced SMAD7 leads to overactivation of TGF-beta signaling in MDS that can be reversed by a specific inhibitor of TGF-beta receptor I kinase; Cancer Res.?71?955
3) Rodon?et al.?(2015),?First-in-human dose study of the novel transforming growth factor-b-receptor I kinase inhibitor LY2157299 monohydrate in patients with advances cancer and glioma; Clin. Cancer Res.?21?553
4) Herbertz?et al. (2015),?Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway; Drug Des. Devel. Ther.?9?4479
5) Brandes?et al.?(2016),?A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma; Neuro. Oncol.?18?1146
6) Tran?et al.?(2017), TGFβR1 Blockade with Galunisertib (LY2157299 Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells; Clin. Cancer Res.?23?804
7) Otegbeye?et al.?(2018),?Inhibiting TGF-beta signaling preserves the function of highly activated, in vitro expanded natural killer cells in AML and colon cancer models; PLoS One?13?e0197008
8) Holmgaard?et al.?(2018),?Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete response, as monotherapy and in combination with checkpoint blockade; J. Immunother. Cancer?6?47
Check Digit Verification of cas no
The CAS Registry Mumber 700874-72-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,0,0,8,7 and 4 respectively; the second part has 2 digits, 7 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 700874-72:
(8*7)+(7*0)+(6*0)+(5*8)+(4*7)+(3*4)+(2*7)+(1*2)=152
152 % 10 = 2
So 700874-72-2 is a valid CAS Registry Number.
700874-72-2Relevant articles and documents
Application of kinetic modeling and competitive solvent hydrolysis in the development of a highly selective hydrolysis of a nitrile to an amide
Niemeier, Jeffry K.,Rothhaar, Roger R.,Vicenzi, Jeffrey T.,Werner, John A.
, p. 410 - 416 (2014/04/17)
A combination of mechanism-guided experimentation and kinetic modeling was used to develop a mild, selective, and robust hydroxide-promoted process for of a nitrile to an amide using a substoichiometric amount of aqueous sodium hydroxide in a mixed water and N-methyl-2-pyrrolidone solvent system. The new process eliminated a major reaction impurity, minimized overhydrolysis of the product amide by selection of a solvent that would be sacrificially hydrolyzed, eliminated genotoxic impurities, and improved the intrinsic safety of the process by eliminating the use of hydrogen peroxide. The process was demonstrated in duplicate on a 90 kg scale, with 89% isolated yield and greater than 99.8% purity.
