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Work in Progress: Drugs in Development

Clin Liver Dis. 2018 Aug;22(3):501-515. doi: 10.1016/j.cld.2018.03.004. Epub 2018 May 17.

Abstract

Primary biliary cholangitis is an archetypal autoimmune disease that causes cholestasis, fibrosis, and liver failure. Ursodeoxycholic acid and obeticholic acid are approved for its treatment. Not all patients respond, some are intolerant, many have ongoing symptoms, and new therapies are required. Herein we describe drugs in development and potential future biological targets. We consider compounds acting on the farnesoid X receptor/fibroblast growth factor 19 pathway, fibrates and other agonists of the peroxisome proliferator-activated receptor family, transmembrane-G-protein-receptor-5 agonists, and several immunological agents. We also consider the roles of bile acid reuptake inhibitors, nalfurafine, and fibrates in pruritus management.

Keywords: Immunomodulators; Novel therapies; Primary biliary cirrhosis; Unmet need.

Publication types

  • Review

MeSH terms

  • Abatacept / therapeutic use
  • Acetates / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / therapeutic use
  • Bezafibrate / therapeutic use
  • CD40 Antigens / antagonists & inhibitors
  • CD40 Ligand / antagonists & inhibitors
  • Chalcones / therapeutic use
  • Chemokine CX3CL1 / antagonists & inhibitors
  • Chenodeoxycholic Acid / analogs & derivatives*
  • Chenodeoxycholic Acid / therapeutic use
  • Cholic Acids / therapeutic use*
  • Drug Development
  • Fenofibrate / therapeutic use
  • Fibroblast Growth Factors / analogs & derivatives*
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Immunosuppressive Agents / therapeutic use*
  • Janus Kinase Inhibitors / therapeutic use
  • Liver Cirrhosis, Biliary / complications
  • Liver Cirrhosis, Biliary / drug therapy*
  • Methylamines / therapeutic use
  • PPAR alpha / agonists
  • PPAR delta / agonists
  • PPAR gamma / agonists
  • Peroxisome Proliferator-Activated Receptors / agonists*
  • Propionates / therapeutic use
  • Pruritus / drug therapy
  • Pruritus / etiology
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, G-Protein-Coupled / agonists
  • Thiazepines / therapeutic use
  • Triazoles / therapeutic use
  • Ustekinumab / therapeutic use

Substances

  • (2-methyl-4-(5-methyl-2-(4-trifluoromethyl-phenyl)-2H-(1,2,3)triazol-4-ylmethylsulfanyl)phenoxy)acetic acid
  • 2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid
  • 3-((((3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl)methyl)amino)pentanedioic acid
  • 6alpha-ethyl-23(S)-methylcholic acid
  • Acetates
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • CD40 Antigens
  • Chalcones
  • Chemokine CX3CL1
  • Cholic Acids
  • FGF19 protein, human
  • GPBAR1 protein, human
  • Hypolipidemic Agents
  • Immunosuppressive Agents
  • Janus Kinase Inhibitors
  • Methylamines
  • PPAR alpha
  • PPAR delta
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptors
  • Propionates
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • Thiazepines
  • Triazoles
  • obeticholic acid
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • CD40 Ligand
  • Fibroblast Growth Factors
  • Abatacept
  • Ustekinumab
  • quetmolimab
  • Fenofibrate
  • Bezafibrate