Pharmaceutical Biocatalysis: Important Enzymes, Novel Targets, and Therapies

Lipase-Mediated Biocatalysis as a Greener and Sustainable Choice for Pharmaceutical ProcessesIntroductionHydrolases as BiocatalystsLipases: A General AccountStructural features of lipasesReaction mechanism of lipasesProperties of lipasesLipase-Catalyzed Synthesis of Active Pharmaceutical Ingredients and IntermediatesNon-steroidal antiinflammatory drugs (NSAIDs)Angiotensin-converting enzyme inhibitorsβ-blocking drugsAntianginal drugs (S)-RanolazineAntiviral drugs Tamiflu (Oseltamivir Phosphate)Antiepileptic drugsThromboxane A2 antagonist: (R)-RamatrobanAntidepressant: Fluoxetine intermediateAnti-Parkinson’s drug: Rasagiline mesylateImproved antibacterials: Chloramphenicol estersPeroxisome proliferator-activated receptor agonist: RagaglitazarAntitumoror drug: DeoxyspergualinAntimycobacterial and antimalarial drug: (R)-thiolactomycinHMG CoA reductase inhibitor: Key intermediate of RosuvastatinCathepsin K inhibitor: Odanacatib intermediateCommercial Success through Green TechnologiesFuture PerspectivesConclusionReferencesPhosphodiesterasesIntroductionClassification of PDE SubfamiliesStructural Aspects of PhosphodiesterasesNon-Specific Inhibition of PhosphodiesterasesPhosphodiesterase 3Structure, Function and Regulation of PDE3Inhibition of PDE3Phosphodiesterase 4Structure, Function and Regulation of PDE4Inhibition of PDE4Phosphodiesterase 5Structure, Function and Regulation of PDE5Inhibition of PDE5Concluding RemarksReferencesHuman DOPA Decarboxylase: Catalysis and Involvement in Pharmacological Treatments for Parkinson’s Disease and Aromatic Amino Acid Decarboxylase DeficiencyIntroductionStructure of DDCCatalysis of DDCDrugs Used to Counteract DDC Loss in PD or Loss-of-Function in AADC DeficiencyConclusionsReferencesAdvancing Phospholipase D Enzymes as Diverse Drug TargetsIntroductionNon-HKD PLD as a Target for Infectious Diseases and EnvenomingNon-HKD PLD as a Target for Cancer, Inflammatory and Neurodegenerative DiseasesHuman PLD Inhibitors Are Potential Drugs for Cancer, Cardiovascular Disease, Infectious Diseases, and Neurodegenerative DiseasesConcluding RemarksReferencesIDH1 and IDH2 Mutations as Novel Therapeutic Targets in Acute Myeloid Leukemia (AML): Current PerspectivesIntroductionNormal Functions of IDH EnzymesIDH Mutants Produce D-2HG and Inhibit alpha-KG-Dependent DioxygenasesIDH Mutations Are Associated with Epigenetic Reprogramming, Altering Cancer Cells Differentiation and DNAIDH Mutations Are Associated with Metabolic ReprogrammingIDH1/2 Mutations in Hematologic MalignanciesD2HG as a Predictive Biomarker in IDH-Mutant CancersTargeting of IDH-Mutant TumorsHypomethylating AgentsIDH-Mutant Enzymes Inhibitors (Preclinical Studies)Clinical Efficacy: FDA-Approved Mutant IDH1/2 Enzymes InhibitorsFrontline studies in combination Intensive treatmentConclusionReferencesEnzymes for Prodrug-Activation in Cancer TherapyIntroductionProdrug-Activating Enzymes and ApplicationsDirected Enzyme Prodrug Activation in Cancer TherapyAntibody-Directed Enzyme Prodrug TherapyGene-Directed Enzyme Prodrug TherapyBacterial-directed enzyme prodrug therapyVirus-directed enzyme prodrug therapyVirus-mediated treatment of familial lipoprotein lipase deficiencyConditionally replicating adenoviruses for cancer therapyChimeric antigen receptor (CAR) T cell therapy and recently FDA-and EMA-approved gene therapiesOther Methods of Directed Enzyme Prodrug ActivationLectin-directed enzyme activated prodrug therapyPolymer-directed enzyme prodrug therapy and polymer enzyme liposome therapyPolymer-directed enzyme prodrug therapyPolymer enzyme liposome therapyMelanocyte-directed enzyme prodrug therapy (MDEPT)ConclusionReferencesSmall-Molecule Inhibitors Targeting Receptor Tyrosine Kinases in CancerIntroductionRTKs Function and StructureTyrosine Kinase Inhibitors (TKIs)EGFR Family and Specific/Selective TKIsVascular Endothelial Growth Factor Receptor and Anti-Angiogenesis TKIsTyrosine Kinase Inhibitors Targeting PDGFRFibroblast Growth Factor Receptor (FGFR)MET oncogeneFms-Like Tyrosine Kinase 3 (FLT3)Receptor Tyrosine Kinase Receptor (R0R1)Anaplastic Lymphocyte KinaseConclusionsReferencesβ-Lactams and Related Compounds as Antibacterials and β-Lactamase InhibitorsIntroductionThe Cell Wall and the Mode of Action of the P-LactamsClasses of β-Lactam AntibioticsThe β-Lactam Antibiotics and Resistancesβ-Lactamase Classes, Mode of Action, and StructureThe Serine-β-LactamasesThe MetallolactamasesFirst-Generation β-Lactamases InhibitorsSecond-Generation β-Lactamases InhibitorsThird-Generation β-Lactamases InhibitorsFuture DevelopmentsReferencesDirect Oral Anticoagulants: New OptionsIntroductionBlood Coagulation and Its Physiological RegulationCoagulation CascadeRegulation of Coagulation CascadeAnticoagulants and Their Common Pharmacological RationaleVitamin К Antagonists (VKA)Clinical SignificanceMode of ActionLarge Variability of ActionMonitoring-Guided DosageDirect Oral Anticoagulants (DOAC)Indications of DOACsCharacteristics of the Drug Substances and PharmacodynamicsPharmacokinetics of the DOACComparison between DOAC and VKADosage of the DOACTypical Patients with Indication for DOAC Dosage of DOAC in Renal InsufficiencyDOAC and ComedicationApplication of DOAC in Clinical PracticeConclusions and OutlookReferencesMolecular Mechanisms for Statin Pleiotropy and Possible Clinical Relevance in Cardiovascular DiseaseIntroductionStatin PharmaceuticsClinical Evidence for Statin PleiotropyMolecular Mechanisms of Statin PleiotropyStatins and Isopyrenylated ProteinsStatins and Rho KinaseStatins and the Peroxisome Proliferator-Activated ReceptorsStatins and RacCellular Effects of StatinsStatins and Endothelial FunctionStatins and Smooth Muscle CellsStatins and the MyocardiumStatins and Atherosclerosis and Vascular InflammationStatins and Ischemic StrokeConclusionReferencesLysosomal Storage Disorders and Enzyme Replacement TherapyIntroductionLysosomal Storage DiseasesSphingolipidosesExamplesGM1-Gangliosidosis, Sialidosis, Tay–Sachs Disease, Sandhoff AB ariantSandhoff Disease, GM1 Gangliosidosis, Fabry DiseaseFarber and Gaucher DiseaseNiemann–Pick DiseasesKrabbe Disease, Metachromatic Leukodystrophy and Multiple Sulfatase DeficiencyPompe DiseaseAlpha MannosidosisMucopolysaccharidosesFunctions and Properties of GAGs: Some CommentsMucopolysaccharidoses: The Different TypesMPS IMPS IIMPS IIIMPS IVMPS VIMPS VIIMPS IXMucopolysaccharidoses: The Treatment OptionsERT for MPS I patientsTreatment of MPS type IITreatment of patients with MPS type IIIERT in MPS IIIA patientsERTand MPS NIBERT and MPS IVAERT for MPS VI patientsMPS VII and ERTRecent Advances and OutlookReferences
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