SB1317

Short Summary : CDK,JAK and FLT inhibitor

Category : Tyrosine Kinase|FLT3

Purity : 0.985

CAS Number : 937270-47-8

Formula : C23H24N4O

Molecular Weight : 372.46

SMILE : CN(C/C=C/CCOC1=CC=CC2=C1)CC3=CC(NC4=NC=CC2=N4)=CC=C3

Solubility : >44.87mg/mL in DMSO

Storage : Store at -20°C

Description : 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 [1].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 [1]. 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 [2]. 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 [2]. 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 [3].References:[1]. William AD, Lee AC, Goh KC, et al. Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(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.[2]. 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. [3]. 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.

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