. Author manuscript; available in PMC: 2018 Aug 1.

Published in final edited form as: Mol Aspects Med. 2017 Jul 1;56:45–53. doi: 10.1016/j.mam.2017.06.001

Table 2.

Targets for Therapeutic Interventions in cholestatic liver injury (Current and Projected)

Current Targets	Mechanisms of Action	(Drugs)
FXR/NR1H4	Alter bile acid homeostasis by repressing CYP7A1	Obetacholic acid, Fibrates, All-trans retinoic acid^, FGF19^)
MDR3/ABCB4	Inducers enhances phosphatidyl choline synthesis and excretion	Fenofibrate, Benzafibrate
BSEP and MRP2	Increase bile acid excretion and bile flow	UDCA and FXR agonists
ASBT	Inhibitors of bile acid uptake in ileum increases bile acid fecal and urinary exception	A4250^; LLuM001^
AE2	Stimulates Cholangiocyte HC0₃⁻ excretion	norURSO^*
Potential Targets: (Suggested by basic mechanistic studies of the pathogenesis of cholestasis)
NTCP/SLC10A1	block hepatic bile acid uptake	Myrcludex B & others in development^*
OSTα/β (SLC51A/B)	block enterohepatic bile acid circulation and decreases bile acid pool size	??
Endoplasmic reticulum	Reducers of ER stress and reactive oxygen species	UDCA
Mitochondria	Stabilize ATPases & MMP	Cyclosporins, others?
Cytokine Receptors	Repress inflammatory response	CVC

Undergoing clinical trials. See (111) for more details.