Comparative pre-clinical evaluation of receptor tyrosine kinase inhibitors for the treatment of multiple myeloma was written by de Brito, Luis R.;Batey, Mike A.;Zhao, Yan;Squires, Matt S.;Maitland, Helen;Leung, Hing Y.;Hall, Andrew G.;Jackson, Graham;Newell, David R.;Irving, Julie A. E.. And the article was included in Leukemia Research in 2011.Quality Control of 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea The following contents are mentioned in the article:
Background: Fibroblast growth factor receptor 3 (FGFR3) is up-regulated as a result of the t(4;14)(p16;q32) translocation that occurs in up to 20% of multiple myeloma (MM) patients. Recent studies have demonstrated that up-regulation of FGFR3 promotes cell survival, growth and drug resistance in malignant plasma cells, both in vitro and in vivo. Therefore, inhibition of FGFR3 signalling is potential target for the chemotherapeutic intervention in t(4;14) MM. Methods: Small mol. receptor tyrosine kinase inhibitors (PD173074, sunitinib (SU-11248), vandetanib (ZD6474) and vatalanib (PTK-787)) with varying degrees of inhibitory activity and selectivity against FGFR, were assessed in Ba/f3 cells expressing ZNF198-FGFR1 and MM cell lines. Cell viability, FGFR3 and ZNF198-FGFR1 phosphorylation and apoptosis were evaluated by growth inhibition assays, immunoblotting and fluorescence-activated cell sorting anal., resp. An in vivo study was performed with sunitinib in t(4;14)-pos. and t(4;14)-neg. human MM tumor xenograft models. Results: PD173074 and sunitinib differentially inhibited the growth of Ba/f3 cells expressing ZNF198-FGFR1 (GI50 = 10 nM and 730 nM, vs. GI50 >1 μM and 2.7 μM for parental cells; p < 0.0001) and t(4;14) pos. MM cell lines (GI50 = 4-10 μM and 1-3 μM, vs. GI50 = 14-15 μM and 4-5 μM for t(4;14) neg. MM cells; p ≤ 0.002). In addition, both PD173074 and sunitinib inhibited the activation of FGFR3 in t(4;14)-pos. MM cells. PD173074 and sunitinib induced an apoptotic response in a concentration and time-dependent manner in a t(4;14)-pos. (PD174073 and sunitinib) but not a t(4;14)-neg. MM cell line (sunitinib only); however, in in vivo tumors derived from the same cell lines, sunitinib was only active in the t(4;14)-neg. model. Conclusions: These data demonstrate that PD173074 and sunitinib are inhibitors of FGFR3 in MM cell lines, and that sunitinib has in vivo activity in a human MM tumor xenograft model. However, caution should be exercised in using the t(4;14) translocation as a predictive biomarker for patient selection in clin. trials with sunitinib. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Quality Control of 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea).
1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Quality Control of 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia