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Homeostasis of multicellular organisms is critically dependent on the correct interpretation of the plethora of signals which cells are exposed to during their lifespan. Various soluble factors… Expand
SB1518 is an innovative pyrimidine-based macrocycle that shows a unique kinase profile with selective inhibition of Janus Kinase-2 (JAK2; IC50=23 and 19 nM for JAK2WT and JAK2V617F, respectively)… Expand
Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2(V617F)), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a… Expand
TG02 is a novel pyrimidine-based multi-kinase inhibitor that inhibits CDKs 1, 2, 7 and 9 together with JAK2 and FLT3. It dose-dependently inhibits signaling pathways downstream of CDKs, JAK2 and FLT3… Expand
Interreceptor cross-talk has emerged as a general concept in cellular signaling cascades. Therein epidermal growth factor receptor (EGFR) signal transactivation represents the so far best… Expand
Phosphoinositide 3-kinases (PI3Ks) and the mammalian target of rapamycin (mTOR) act as critical effectors in a commonly deregulated cell signaling pathway in human cancers. The abnormal activation of… Expand
Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization… Expand
e13549 Background: Kinase inhibitors have found applications in oncology due to their ability to target key signaling pathways in many different cancers. In general, broad-spectrum kinase inhibitor...
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