Increased potency achieved through macrocyclization is also exemplified in work by S*Bio leading to the pan-CDK/JAK2/FLT3 inhibitor SB1317, also known as TG02 ( ), an oral compound currently in clinical trials under the generic name zotiraciclib for the treatment of glioblastoma multiforme and diffuse intrinsic pontine glioma (Figure ). Initial screening against Aurora A kinase led to the identification of hits with sub-micromolar affinity. These hits contained a common acyclic aniline-pyrimidine scaffold which was well documented in the literature to be promiscuous for kinase inhibition and was also heavily patented. Docking these compounds into the Aurora A kinase active site indicated a U-shaped bound conformation that the authors hypothesized would lend itself well to macrocyclization. The resulting macrocyclic compounds in fact proved to have greater activity against other kinases, compared to Aurora A, including cyclin dependent kinases (CDKs) and the FMS-like tyrosine kinase-3 (FLT3). Comparison of the acyclic ring closing metathesis substrate, 6, to the resulting cyclized compound, 5, allows estimation of the impact of cyclization on the potency of inhibition of these other kinases.