Compound 22 caused the dephosphorylation of Akt at Ser 473 and other ILK goals, including glycogen synthase kinase 3B and myosin Lapatinib solubility light chain. Moreover, 22 suppressed the expression of the transcription/translation issue YB 1 and its objectives HER2 and EGFR in PC 3 cells, that could be rescued from the stable expression of constitutively active ILK. Research indicates that 22 induced autophagy and apoptosis, both which were integral to its antiproliferative activity. Together, this broad-spectrum of mechanisms underlies the therapeutic potential of 22 in cancer treatment, which is manifested by its in vivo efficacy as a single oral agent in PC 3 xenograft tumor growth. Launch The phosphatidylinositol 3 kinase /Akt signaling axis plays a critical role in controlling numerous cellular activities including cell growth, emergency, metabolism, and motility through the modulation of a variety of downstream effectors. In reaction to growth factor or cytokine stimulation, activated PI3K encourages the generation of phosphatidylinositol 3,4,5 trisphosphate, biological cells leading to the membrane recruitment and subsequent causing phosphorylation of Akt at Thr 308 and Ser 473 by phosphoinositide dependent kinase PDK2 and 1, respectively. Contrary to the well characterized PDK1,1 the molecular identity of PDK2 remains elusive. 2 Although recent evidence has suggested that the rictormTOR complex acts as a PDK2,3,4 numerous other kinases are also implicated in mediating Akt Ser 473 phosphorylation,2 one of which is integrin linked kinase. 5 7 ILK was originally recognized as a binding companion of the cytoplasmic tail of integrin B1 through a yeast two hybrid screening. 8 The ILK protein includes three main domains, a central pleckstrin homology domain, specifically the N terminal ankyrin repeats, and Cterminal kinase domain. 9 Each one of these domains plays a role in mediating ILKs biological features through interaction with small molecule Hedgehog antagonists intracellular signaling proteins or PIP3. As an example, ILK bodily interacts with the cytoplasmic proteins PINCH and parvin to create the ternary ILK PINCH parvin complex, which serves as a molecular scaffold relating integrins with actin cytoskeleton10 and the microtubule network11 to modulate actin polymerization and mitotic spindle orientation, respectively. Though whether a functional kinase domain is contained by ILK remains a contentious issue,12 ILK is shown to mediate the phosphorylation of various signaling proteins, including Akt at Ser 473, glycogen synthase kinase 3B, and myosin light chain. 14,15 Furthermore, ILK over-expression has been linked to the cyst development and oncogenesis of several types of malignancies, including those of prostate,16 ovary,17 breast,18 colon,19 pancreas,20 stomach,21 and liver. 22 In light of its role in regulating diverse cellular activities, including cell growth, success, angiogenesis, mobility, and epithelial mesenchymal transition, ILK presents a relevant target for cancer therapy.