700874-72-2 Usage
Uses
Used in Cancer Therapy:
LY 2157299 is used as an inhibitor of TGF-β signaling for the study of chemotherapy-induced expansion of cancer stem-like cells in triple-negative breast cancer cell lines and xenografts. It also inhibits the migration and tumor growth of hepatocellular carcinoma cell lines by disrupting Smad-2 phosphorylation.
Used in Enhancing Chemotherapy Action:
In the field of oncology, LY 2157299 is used as a TGF-β type I receptor kinase inhibitor to enhance the action of chemotherapy against triple-negative breast cancer (TNBC).
Used in NK Cell Therapy:
In immunotherapy, LY 2157299 is used to augment the anti-tumor cytotoxicity of activated NK (aNK) cells. It suppresses SMAD2 phosphorylation and restores the expression of DNAX Accessory Molecule-1, NKp30, NKG2D, and TNF-related apoptosis-inducing ligand death ligand on aNK cells. Additionally, it enhances the release of perforin and granzyme A from aNK cells, improving their direct cytotoxicity and ADCC against neuroblastoma cells in vitro.
Used in Adoptive NK Cell Therapy:
In the context of adoptive NK cell therapy, LY 2157299 is used to preserve the cytotoxic function of ex vivo expanded, highly activated NK cells. It significantly improves the eradication of liver metastases of colon cancer in mice treated with adoptive NK cells, demonstrating that targeting TGF-beta signaling in vivo can markedly enhance the therapeutic efficacy of adoptive NK cell therapy.
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 academic research and scientific papers
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.
QUINOLINYL-PYRROLOPYRAZOLES
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Page 10, (2010/02/07)
A compound according to formula II and the pharmaceutically acceptable salts thereof and the method of treating cancer in a patient in need thereof by administration of said compound.
