Appearance:white solid powder
Purity: > 98%
SB1317(TG-02, cas 937270-47-8) is a novel small molecule potent CDK2/JAK2/FLT3 inhibitor with IC50s of 13/73/56 nM respectively.
SB1317 was soluble, highly permeable in Caco-2 cells, and showed > 99% binding to plasma from mice, dog and humans. It was metabolically stable in human and dog liver microsomes relative to mouse and rat. SB1317 was mainly metabolized by CYP3A4 and CY1A2 in vitro. SB1317 did not inhibit any of the major human CYPs in vitro except CYP2D6 (IC50=1 μM). SB1317 did not significantly induce CYP1A and CYP3A4 in human hepatocytes in vitro.
1:Structure-based design of nitrogen-linked macrocyclic kinase inhibitors leading to the clinical candidate SB1317/TG02, a potent inhibitor of cyclin dependant kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3). Poulsen A, William A, Blanchard S, Nagaraj H, Williams M, Wang H, Lee A, Sun E, Teo EL, Tan E, Goh KC, Dymock B.J Mol Model. 2013 Jan;19(1):119-30. doi: 10.1007/s00894-012-1528-7. Epub 2012 Jul 22. PMID: 22820730
2:Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Pasha MK, Jayaraman R, Reddy VP, Yeo P, Goh E, Williams A, Goh KC, Kantharaj E.Drug Metab Lett. 2012 Mar;6(1):33-42. PMID: 22372550
3:Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[188.8.131.52(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. William AD, Lee AC, Goh KC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Lee CP, Wang H, Williams M, Sun ET, Hu C, Jayaraman R, Pasha MK, Ethirajulu K, Wood JM, Dymock BW.J Med Chem. 2012 Jan 12;55(1):169-96. doi: 10.1021/jm201112g. Epub 2011 Dec 29. PMID: 22148278