SB1317 is a potent inhibitor of Cyclin dependent kinases (CDKs), FMS-like tyrosine kinase-3 (FLT3) and Janus kinase 2 (JAK2) with IC50 values of 13nM, 56nM and 73nM for CDK2, JAK2 and FLT3, respectively .
CDKs are serine-threonine kinases that regulating the cell cycle. JAK2 is a nonreciprocal intracellular tyrosine kinase that transduces cytokine-mediated signals via the JAK-STAT pathway. FLT3 is a cytokine receptor and plays an important role in the normal development of haematopoietic stem cells .
In luciferase-expressing MM1S cells, SB1317 overcame the proliferative/protective advantage conferred by IL-6. In MM1S cells, SB1317 increased the percentage of cells in G2/M phases and decreased cells in the S phase. Also, SB1317 increased the amount of cells in the subG0 region .
In CB17-SCID mice bearing human multiple myeloma plasmacytoma xenograft models (the bortezomib-sensitive MM1S model and the more bortezomib-resistant OPM2 model), SB1317 significantly inhibited tumor growth . In a subcutaneous AML model, treatment mice with SB1317 dosed 10, 20 or 40 mg/kg daily for 21 days reduced the average tumor volume by 53%, 61% and 113%, respectively .
. William AD, Lee AC, Goh KC, et al. Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[18.104.22.168(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer. J Med Chem, 2012, 55(1): 169-196.
. Álvarez-Fernández S, Ortiz-Ruiz MJ, Parrott T, et al. Potent antimyeloma activity of a novel ERK5/CDK inhibitor. Clin Cancer Res, 2013, 19(10): 2677-2687.
. Goh KC, Novotny-Diermayr V, Hart S, et al. TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia, 2012, 26(2): 236-243.
|Storage||Store at -20°C|
|Synonyms||TG02;SB 1317;TG 02;SB-1317;TG-02|
|Solubility||≥44.87 mg/mL in DMSO, ≥3.98 mg/mL in EtOH with ultrasonic and warming, <2.36 mg/mL in H2O|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|