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Biocatalysis has emerged as a transformative approach in sustainable drug synthesis. This article provides an extensive overview of key enzymes harnessed in biocatalysis and their diverse applications in eco-friendly drug development. Cytochrome P450 enzymes enable the hydroxylation of drug precursors, metabolite generation for toxicity assessment and chiral drug intermediate synthesis. Lipases contribute to asymmetric ester prodrug synthesis and racemic mixture resolution, while proteases are instrumental in peptide bond formation and peptide-based drug synthesis. Transaminases facilitate chiral amine synthesis and amino acid derivative production for drugs. Dehydrogenases allow stereoselective ketone reduction and chiral alcohol production. Aldolases enable enantioselective aldol reactions and key drug intermediate formation. DNA ligases aid in DNA-based drug development and targeted drug delivery. Nitrilases promote nitrile hydrolysis and green amide synthesis. Kinases play roles in prodrug activation and drug target validation. Methyltransferases are vital for small molecule methylation and epigenetic drug discovery. Oxidoreductases enable redox reactions and aldehyde-ketone interconversion. Glycosyltransferases contribute to drug candidate glycosylation and bioconjugation. Biocatalysis offers a sustainable alternative, aligning with pharmaceutical industries’ commitment to environmentally responsible drug discovery and production, as supported by the referenced literature. [ABSTRACT FROM AUTHOR]

Diabetes is a prevalent metabolic disorder that results in several comorbidities including cancer. Cancer becomes the most severe complication of diabetes patients. Growing evidence proved that impaired glucose homeostasis is an independent risk factor for the occurrence of various types of cancers including liver, pancreatic, gastric (stomach), colorectal, kidney, and breast cancers, and influences cancer prognosis. Diabetes mellitus and cancer have a bidirectional relationship, thus there is a need to look for drugs that can be beneficial in treating both diseases. Therefore, more research is focusing on evaluating the role of antihyperglycemic agents in the treatment of various types of cancers. Metformin, an FDA-approved first-line antihyperglycemic agent can be used as a monotherapy or as an adjuvant to chemotherapeutic agents in the treatment of various types of cancer. However, the exact mechanism of metformin as an anticancer agent is still unknown, the majority of the described putative mechanisms focus on promoting the activity of the AMP-activated protein kinase (AMPK) pathway. This review article thus gives insights into the prognosis of cancer in diabetes patients and aims to explore the possible mechanism of action of metformin in the prevention and treatment of cancer. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are highly prevalent gastrointestinal disorders. Traditional symptoms based therapies had somewhat limited success and efficacy in addressing the disorders. Recently, linaclotide emerged as novel peptide capable of improving abdominal symptoms in patients suffering from IBS-C and CIC. Guanylate cyclase C (GC-C) receptor a multi domain protein, found to be molecular target for linaclotide which acts by activating GC-C receptor on the apical surface of intestinal epithelial cells. Binding of linaclotide to GC-C receptor triggers the elevation of second messenger cGMP that elicits fluid secretion into intestinal cells which play a critical role in maintaining homeostasis through cystic fibrosis transmembrane conductance regulator (CFTR). Data from Phase II and III clinical trials demonstrated that linaclotide seems to produce a statistically significant increase in stool frequency, improved straining, decreased abdominal pain and discomfort.

Prostate cancer is the most common malignancy among men found to be the second leading cause of male cancer-related mortality due to development of resistance against androgen deprivation therapy (ADT). With the advancement in understanding of prostate cancer, numbers of agents have been emerged to target Androgen-Receptor (AR) signaling for the treatment of castration resistant prostate cancer (CRPC). Food and Drug Administration (FDA) has recently approved enzalutamide (XTANDI) for the treatment of CRPC. Androgen receptor promotes the prostate cancer progression after transformation. Androgen receptor signaling leads to CRPC when cellular nucleus binds to DNA and increases pro cancer gene expression. In phase ΙΙΙ clinical trial, enzalutamide showed that 160 mg once daily oral administration is well tolerated and significantly enhanced overall survival in men with CRPC after chemotherapy, demonstrated by reduction in the serum prostate specific antigen (PSA) level and increased survival rate by 4.8 months.

Cabazitaxel has recently been approved by FDA for the treatment of docetaxel resistant hormone-refractory prostate cancer. It has been developed by Sanofi-Aventis under the trade name of Jevtana. It is given in combination with prednisone/prednisolone and has passed the clinical trial over well-known drug mitoxantrone. This drug is a microtubule depolymerization inhibitor, which can penetrate blood brain barrier (BBB). The FDA granted fast track designation to this drug in November 2009 and thereafter, new drug application submission was done in March 2010. Priority review to this drug was granted in April 2010 and finally in July 2010 it was approved by FDA. It is available in the form of injection in the dose of 60 mg/1.5 mL, which should be diluted prior to its use by the diluents supplied along with the injection. It is a second-line drug and has proven to be effective in patients experiencing docetaxel based treatment failure.

Angiogenesis is the process of formation of new blood vessels due to over expression of VEGF (vascular endothelial growth factor) which plays a critical role in the growth and development of all solid tumor types. With the advancement in understanding of tumor angiogenesis and VEGF, there have been a number of agents developed to target VEGF for the treatment of cancer. These targeted agents can affect downstream VEGF signal transduction by unique mechanisms at different cellular and extracellular levels. FDA has recently approved Aflibercept or VEGF-Trap in August 2012 for the treatment of colorectal cancer. It is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting VEGF-A, VEGF-B and placental growth factor. VEGF-Trap exerts its antiangiogenic effects through regression of tumor vasculature, remodelling or normalization of surviving vasculature and inhibition of new tumor vessel growth. In this review, pre-clinical and clinical data have been summarized for aflibercept alone and in combination with chemotherapy to explore its efficacy and benefits in ovarian cancer, breast cancer, non-small cell lung cancer, pancreatic cancer, glioblastoma, adenocarcinoma and renal cell cancer xenograft models.