Arachidonate 5-lipoxygenase (ALOX5) is belongs to lipoxygenase family of enzymes. It metamorphose essential fatty acids substrates into leukotrienes as well as a wide range of other biologically active products. Pancreatic adenocarcinoma remains one of the most fatal animocity. The incidence of pancreatic cancer has steadily increased over the past four decades. Almost 30% of patients with pancreatic cancer present with large, locally advanced tumors in the absence of distant metastases. Because surgical resection is frequently contraindicated by vascular invasion, locally advanced pancreatic cancer has a dismal prognosis with a 6-10-month median survival. The majority of patients present with advanced disease at time of diagnosis resulting in a 5-year survival rate of 7%.Previous studies shown that 5-lipoxygenase (5-LOX) mRNA and protein are expressed in human pancreatic cancer cell lines and that triptolide treatment significantly down regulates 5-LOX expression. Furthermore, LOX inhibitors were found to block proliferation of human pancreatic cancer cells whereas the LOX metabolites 5-HETE and 12-HETE were found to stimulate cancer growth through activation of the p44/42 mitogen-activated protein kinase and PI3/Akt kinase pathways. ALOX5 products, particularly 5-hydroxyeicosatetraenoic acid and 5-oxo-eicosatetraenoic acid, promote the proliferation of these ALOX5 aberrantly expressing tumor cell lines suggesting that ALOX5 acts as a pro-malignancy factor for them and by extension their parent tumors. Thus, for deterrence and treatment of pancreatic cancer induction of 15-LOX-1 expression may be an attractive option for the.5-LOX-derived leukotriene in the pathogenesis of cancer.
The present appraisal is sought to identify a high affinity molecule targeting against ALOX 5 for the treatment of pancreatic cancer through molecular docking studies. 27 established compounds were obtained from various literature studies. The ligand compounds were further prepared using Schrodinger suit software. Protein 3D structure of ALOX5 was obtained from Protein Data Bank(PDB) using PDB ID: 3V92 . Molecular docking studies was performed using flexible docking software, Molegro Virtual Docker. The compound AM-679(Pubchem cid: 71308150), found to be the most effective compound which bound with ALOX5. Further studies can be perform on AM-679 by employ molecular descriptors, Virtual Screening, ADMET, Pharamacophore, Pharmacokinetics studies etc.