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- Ocaliva (obeticholic acid) / Intercept
METABOLIC DISEASE TREATMENT BY MIR-22 INHIBITOR AND OBETICHOLIC ACID VIA FGF21 AND FGFR1 INDUCTION (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1654;
The simultaneous induction of miR-22 as well as FGF21 and its receptor by metabolic stimulators may maintain FGF21 sensitivity and restrict persistent ERK1/2 activation. Reducing miR-22 enhances hepatic FGF21 and activates AMPK, which is an effective approach to improving insulin sensitivity and treating steatosis.
- Ocaliva (obeticholic acid) / Intercept
MORTALITY RISK OF PATIENTS WITH HEPATIC DECOMPENSATION FROM PRIMARY BILIARY CHOLANGITIS IN THE OBETICHOLIC ACID ERA (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1599;
The risk of death of CTP B/C PBC patients in the OCA era was lower than expected. Whether this reduction in mortality risk is causally related to OCA is unknown; however, at least at the population level, there seems no evidence that indiscriminate use of OCA may have resulted in increased mortality.
- Ocaliva (obeticholic acid) / Intercept
OBETICHOLIC ACID (OCA) IMPROVES NON-INVASIVE MARKERS OF FIBROSIS IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS (NASH): A SECONDARY ANALYSIS OF THE PHASE 3 REGENERATE STUDY (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1476;
Liver stiffness as assessed by TE also improved over time, with a clear, dose-dependent reduction by month 18, consistent with histologic improvement seen in REGENERATE. Interim analysis results at 18 months are based on surrogate endpoints and impact on clinical outcomes has not been confirmed.
- Ocaliva (obeticholic acid) / Intercept, Lacromid (bezafibrate) / Remedica
OBETICHOLIC ACID AND BEZAFIBRATE IN PRIMARY BILIARY CHOLANGITIS: A COMPARATIVE EVALUATION OF EFFICACY THROUGH REAL WORLD CLINICAL PRACTICE (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1475;
Discontinuation rates are higher than previously reported, with BZF leading to significant rises in bilirubin in 10% of pts. Randomized controlled trials addressing the safety and efficacy of therapies (alone or in combination) remain warranted.
- Ocaliva (obeticholic acid) / Intercept
OBETICHOLIC ACID IMPROVES HEPATOBILIARY SECRETION OF BILE ACIDS IN PATIENTS WITH PBC (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1474;
This 11 C-CSar PET study in PBC patients shows that OCA improves the hepatic uptake and biliary secretion of bile acids thus reducing bile acid load in the hepatocytes. These “first-in-man” findings demonstrate OCA-mediated anti-cholestatic effects and increase the understanding of PBC pathophysiology.
- Ocaliva (obeticholic acid) / Intercept
OBETICHOLIC ACID TREATMENT IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS: A SECONDARY ANALYSIS OF THE REGENERATE STUDY ACROSS FIBROSIS STAGES (Hynes Convention Center, Auditorium) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1473;
Interim analysis results at 18 months are based on surrogate endpoints and impact on clinical outcomes has not been confirmed. The REGENERATE study is ongoing to confirm the clinical benefit of OCA.
- TERN-101 / Terns Pharma
PHARMACOKINETICS, TISSUE DISTRIBUTION AND PHARMACODYNAMICS OF TERN-101, A NOVEL FARNESOID X RECEPTOR (FXR) AGONIST, IN PRECLINICAL SPECIES (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1335;
Direct hepatic agonism of FXR has the potential advantage of modulating liver-specific metabolic pathways while mitigating non-liver mediated adverse effects. Taken together, these data support further clinical development of TERN-101 for the treatment of NASH.
- PHARMACOLOGICAL VALIDATION AND RNA-SEQ GENE EXPRESSION PROFILING OF TWO RODENT MODELS OF NASH, NEW MECHANISTIC INSIGHTS AND IMPLICATIONS (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1334;
Either model could be pharmacologically validated with compounds of different MOAs. The demonstration of efficacy of these compounds could be mutually exclusive.
- Ocaliva (obeticholic acid) / Intercept
REAL WORLD EXPERIENCE WITH OBETICHOLIC ACID IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS – MULTICENTRIC AUSTRIAN ANALYSIS (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1174;
The demonstration of efficacy of these compounds could be mutually exclusive. The second-line therapy with obeticholic acid is effective and safe in patients with PBC also in a real-world setting
- Ocaliva (obeticholic acid) / Intercept
SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF OBETICHOLIC ACID IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS AND FIBROSIS OR CIRRHOSIS (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1077;
Plasma exposure of total OCA was highest in F4 patients, however liver concentrations were similar or modestly higher with higher fibrosis score. Results are consistent with a disproportionate increase in plasma exposure of OCA in more advanced patients relative to the liver exposure (primary site of action for therapy).
- Ocaliva (obeticholic acid) / Intercept
THE IMPACT OF PRURITUS ON PATIENT-REPORTED OUTCOMES (PROs) IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS (NASH) TREATED WITH OBETICHOLIC ACID (OCA) (Hynes Convention Center, Room 312) - Sep 29, 2019 - Abstract #AASLD2019AASLD_828;
Pruritus with OCA 25 mg seems to be relatively mild without detectable negative impact on PROs. The peak severity of pruritus with OCA 25 mg was observed early in the treatment course without subsequent worsening.1 Interim analysis results at 18 months are based on surrogate endpoints and impact on clinical outcomes has not been confirmed.
- Januvia (sitagliptin) / Merck (MSD)
THE POTENTIAL EFFECT OF COMBINATION THERAPIES WITH A FARNESOID X RECEPTOR (FXR) AGONIST ON HEPATIC FIBROGENESIS IN RAT NASH MODEL (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_795;
Combining INT747 with either LO or SI have a synergistic repressive effect on HF by reversing LPS-induced gut barrier dysfunction and suppressing HSC proliferation. FXR agonist based combination therapies may represent novel therapeutic strategies for NASH.
- | Journal: Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2-Mediated Water Homeostasis. (Pubmed Central) - Sep 28, 2019
TGR5 stimulation increases renal AQP2 expression and improves impaired urinary concentration in lithium-induced NDI. TGR5 is thus involved in regulating water metabolism in the kidney.
- | Ocaliva (obeticholic acid) / Intercept
Trial completion date, Trial primary completion date: Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients (clinicaltrials.gov) - Sep 23, 2019
P2, N=20, Recruiting, Sponsor: University of Texas Southwestern Medical Center
TGR5 is thus involved in regulating water metabolism in the kidney. Trial completion date: Dec 2019 --> Dec 2020 | Trial primary completion date: Jun 2019 --> Jun 2020
- | elafibranor (GFT505) / Genfit, Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Disease Progression and Pharmacological Intervention in a Nutrient-Deficient Rat Model of Nonalcoholic Steatohepatitis. (Pubmed Central) - Sep 22, 2019
Trial completion date: Dec 2019 --> Dec 2020 | Trial primary completion date: Jun 2019 --> Jun 2020 CDAA-fed rats develop early-onset progressive NASH, which offers the opportunity to probe anti-NASH compounds with potential disease-modifying properties.
- | Ocaliva (obeticholic acid) / Intercept
Enrollment change: Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT (clinicaltrials.gov) - Sep 16, 2019
P=N/A, N=70, Recruiting, Sponsor: Sir Salimullah Medical College Mitford Hospital
CDAA-fed rats develop early-onset progressive NASH, which offers the opportunity to probe anti-NASH compounds with potential disease-modifying properties. N=150 --> 70
- | Ocaliva (obeticholic acid) / Intercept
Journal: Metabolism of obeticholic acid in brown bullhead (Ameiurus nebulosus). (Pubmed Central) - Sep 16, 2019
In addition, metabolites of obeticholic acid (sulphate and glucuronide) and several hydroxy-obeticholic acid derivatives were found, representing typical pathways of primary and secondary steroid metabolism. Brown bullhead exposed to obeticholic acid at a dose of 100 mg/kg gave no overt signs of distress or toxicity.
- | Ocaliva (obeticholic acid) / Intercept
Biomarker, Review, Journal: Drug Development for Nonalcoholic Fatty Liver Disease: Landscape and Challenges. (Pubmed Central) - Sep 15, 2019
Smooth collaboration between bench scientists, biotechnology, pharmaceutical industries, and clinicians will be pivotal to target identification, development of effective therapies, biomarker discovery, and ultimately to bring pipeline drugs to market. This review examines the key challenges remaining in NAFLD drug development, outlines early and late phase clinical trials of candidate treatments, and discusses the journey toward biomarker discovery which may facilitate development of novel endpoints in NAFLD clinical trials, enabling meaningful response to be determined noninvasively.
- | Lacromid (bezafibrate) / Remedica
Review, Journal: Primary biliary cholangitis-established and novel therapies (Pubmed Central) - Sep 14, 2019
Patients with insufficient treatment response or risk factors have to be treated consequently. Due to the improved anti-cholestatic treatment options, therapies to reduce fatigue and pruritus are increasingly important.
- | tropifexor (LJN452) / Novartis, Ocaliva (obeticholic acid) / Intercept, cilofexor (GS-9674) / Gilead
Clinical, Journal: Nonsteroidal FXR Ligands: Current Status and Clinical Applications. (Pubmed Central) - Sep 14, 2019
Clinical efficacy superior to most other treatment options was shown by FXR agonists such as obeticholic acid (OCA) as they improved various metabolic features including liver steatosis as well as liver inflammation and fibrosis...Therefore a quest for novel, proprietary FXR agonists is ongoing with the aim to increase FXR potency and selectivity over other proteins and to overcome at least some of the OCA-associated clinical side effects through an improved pharmacology. In this chapter we will discuss the historical and ongoing efforts in the identification and development of nonsteroidal, which largely means non-bile acid-type, FXR agonists for clinical use.
- | Ocaliva (obeticholic acid) / Intercept
Biomarker, Journal: Obeticholic Acid: An Update of Its Pharmacological Activities in Liver Disorders. (Pubmed Central) - Sep 14, 2019
Phase II and III trials have shown that OCA might attenuate the severity of liver fibrosis in patients with NASH, but it has no efficacy in reversing the steatotic component of the disease, while reduces the circulating levels of HDL-C and increases LDL-C. In summary, OCA has been the first-in-class of FXR ligands advanced to a clinical stage and is now entering its third decade of life, highlighting the potential benefits and risk linked to FXR-targeted therapies.
- | Ocaliva (obeticholic acid) / Intercept
Journal: The Pharmacology of Bile Acids and Their Receptors. (Pubmed Central) - Sep 14, 2019
Currently, in addition to obeticholic acid, a semisynthetic derivative of CDCA and the first in class of FXR ligands approved for clinical use, either selective or dual FXR and GPBAR1 ligands, have been developed, and some of them are undergoing pre-approval trials. The effects of FXR and GPBAR1 ligands in different therapeutic area are reviewed.
- | Ocaliva (obeticholic acid) / Intercept
Journal: Targeting FXR in Cholestasis. (Pubmed Central) - Sep 14, 2019
Further FXR agonists as well as a FGF19 analogue are currently tested in clinical trials for different cholestatic liver diseases. This chapter will summarize the current knowledge on the role of FXR in cholestasis both in rodent models and in human diseases.
- | Ocaliva (obeticholic acid) / Intercept
Trial completion date, Trial primary completion date: Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT (clinicaltrials.gov) - Sep 11, 2019
P=N/A, N=150, Recruiting, Sponsor: Sir Salimullah Medical College Mitford Hospital
This chapter will summarize the current knowledge on the role of FXR in cholestasis both in rodent models and in human diseases. Trial completion date: Oct 2019 --> Mar 2020 | Trial primary completion date: Jul 2019 --> Dec 2019
- | linerixibat (GSK2330672) / GSK
Enrollment open: Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects (clinicaltrials.gov) - Sep 11, 2019
P1, N=19, Recruiting, Sponsor: GlaxoSmithKline
Trial completion date: Oct 2019 --> Mar 2020 | Trial primary completion date: Jul 2019 --> Dec 2019 Not yet recruiting --> Recruiting
- | INT-767 / Intercept
Journal: Simultaneous inhibition of FXR and TGR5 exacerbates atherosclerotic formation. (Pubmed Central) - Sep 11, 2019
We demonstrated that 1) FXR and TGR5 dual deficiency exacerbated the development of atherosclerosis and 2) the anti-atherogenic effect of INT-767 requires the anti-inflammatory effect but not the lipid-lowering effect through the simultaneous activation of FXR and TGR5. Our results indicate that dual activation of FXR and TGR5 is a promising strategy for treating atherosclerosis.
- | Ocaliva (obeticholic acid) / Intercept
Journal: Identification of a novel function of hepatic long-chain acyl-CoA synthetase-1 (ACSL1) in bile acid synthesis and its regulation by bile acid-activated farnesoid X receptor. (Pubmed Central) - Sep 11, 2019
Furthermore, we discovered that Acsl1 is a novel molecular target of the bile acid-activated farnesoid X receptor (FXR). Activation of FXR by agonist obeticholic acid repressed the expression of ACSL1 protein and mRNA in the liver of FXR wild-type mice but not in FXR knockout mice.
- | Ocaliva (obeticholic acid) / Intercept
Journal: UGT-dependent regioselective glucuronidation of ursodeoxycholic acid and obeticholic acid and selective transport of the consequent acyl glucuronides by OATP1B1 and 1B3. (Pubmed Central) - Sep 10, 2019
Further uptake studies revealed that OATP1B1- and 1B3-transfected cells could selectively uptake UDCA acyl glucuronide, but not UDCA, OCA, and OCA acyl glucuronide. In summary, the liver disposition of OCA is different from that of UDCA due to hepatic uptake, and liver accumulation of UDCA acyl glucuronide might be related to the perplexing toxicities of UDCA.
- | P3 data, Review, Journal: Phase 3 drug pipelines in the treatment of NASH. (Pubmed Central) - Sep 10, 2019
However, the fact that the race to develop an effective drug against NASH has reached the home stretch, with five drug candidates (obeticholic acid, elafibranor, selonsertib, cenicriviroc, and resmetirom) in phase 3 stage of the trial, is welcome news for patients. The very earliest a NASH drug could hit the market is 2021, assuming all goes well as planned.
- | Lacromid (bezafibrate) / Remedica
Retrospective data, Journal: Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials. (Pubmed Central) - Sep 3, 2019
None of the adverse effects differed statistically between the 2 groups. UDCA and bezafibrate combined treatment is superior to UDCA alone in UDCA non-responders with regard to decreasing liver biochemistry markers, without any significant increase in side effects in patients with PBC.
- | Ocaliva (obeticholic acid) / Intercept
New trial: PBC-Cohort: Prospective, Multicenter Cohort Study on Primary Biliary Cholangitis (clinicaltrials.gov) - Sep 3, 2019
P, N=1200, Not yet recruiting, Sponsor: University of Leipzig
- | Ocaliva (obeticholic acid) / Intercept
Journal: Letter: long-term treatment of severe bile acid diarrhoea-obeticholic acid can normalise SeHCAT retention. (Pubmed Central) - Sep 1, 2019
UDCA and bezafibrate combined treatment is superior to UDCA alone in UDCA non-responders with regard to decreasing liver biochemistry markers, without any significant increase in side effects in patients with PBC. No abstract available
- | Ocaliva (obeticholic acid) / Intercept
Journal: Letter: long-term treatment of severe bile acid diarrhoea-obeticholic acid can normalise SeHCAT retention. Authors' reply. (Pubmed Central) - Sep 1, 2019
No abstract available No abstract available
- | INT-767 / Intercept
Journal: INT-767 prevents NASH and promotes visceral fat brown adipogenesis and mitochondrial function. (Pubmed Central) - Aug 23, 2019
INT-767 also induces a significant reduction of fatty acid synthesis and fibrosis markers, while increasing lipid handling, insulin signaling and mitochondrial markers. In conclusion, INT-767 significantly counteracts HFD-induced liver and fat alterations, restoring insulin sensitivity and prompting preadipocytes differentiation toward a metabolically healthy phenotype.
- | Ocaliva (obeticholic acid) / Intercept
PK/PD data, Preclinical, Journal: An ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of obeticholic acid in rat plasma and its application in preclinical pharmacokinetic studies. (Pubmed Central) - Aug 22, 2019
A specific, sensitive and reliable quantitative analysis method was established to detect OCA after oral/intravenous administration in rat plasma via UPLC-MS/MS. It was appropriate for preclinical pharmacokinetic studies of OCA.
- | Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: FXR Activation by Obeticholic Acid or Non-Steroidal Agonists Induces a Human-Like Lipoprotein Cholesterol Change in Mice with Humanized Chimeric Liver. (Pubmed Central) - Aug 21, 2019
Co-treatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-c. Treatment with two clinically-relevant non-steroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting the increase in circulating LDL-c is a class effect of FXR activation.
- Ocaliva (obeticholic acid) / Intercept
REAL WORLD EXPERIENCE WITH OBETICHOLIC ACID IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS - MULTICENTRIC AUSTRIAN ANALYSIS (Poster Exhibition - Hall 7) - Aug 18, 2019 - Abstract #UEGW2019UEGW_3054;
Treatment with two clinically-relevant non-steroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting the increase in circulating LDL-c is a class effect of FXR activation. The second-line therapy with obeticholic acid is effective and safe in patients with PBC also in a real-world setting.
- Ocaliva (obeticholic acid) / Intercept
POSITIVE RESULTS FROM REGENERATE: A PHASE 3 INTERNATIONAL, RANDOMIZED, PLACEBO-CONTROLLED STUDY EVALUATING OBETICHOLIC ACID TREATMENT FOR NONALCOHOLIC STEATOHEPATITIS (F2) - Aug 18, 2019 - Abstract #UEGW2019UEGW_2830;
Introduction: Obeticholic acid (OCA), an FXR agonist, improved both fibrosis and histologic features of nonalcoholic steatohepatitis (NASH) in the Ph2 FLINT study. Treatment with OCA 25 mg improved liver fibrosis, key histologic features of steatohepatitis and liver biochemistry, demonstrating consistent efficacy with an overall AE profile similar to previous studies.
- |||| Ocaliva (obeticholic acid) / Intercept
Gut vascular barrier disruption by microbiota is an early step in the development of nonalcoholic steatohepatitis and a target for obeticholic acid via β-catenin activation in endothelial cells https://t.co/pOdVq5NaVa (Twitter) - Aug 17, 2019
- | Ocaliva (obeticholic acid) / Intercept
Enrollment change, Trial completion date, Trial primary completion date: REVERSE: Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (clinicaltrials.gov) - Aug 14, 2019
P3, N=900, Recruiting, Sponsor: Intercept Pharmaceuticals
Treatment with OCA 25 mg improved liver fibrosis, key histologic features of steatohepatitis and liver biochemistry, demonstrating consistent efficacy with an overall AE profile similar to previous studies. N=540 --> 900 | Trial completion date: Jul 2021 --> Jun 2022 | Trial primary completion date: Jul 2020 --> Jun 2021
- | linerixibat (GSK2330672) / GSK
New P1 trial: Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects (clinicaltrials.gov) - Aug 11, 2019
P1, N=19, Not yet recruiting, Sponsor: GlaxoSmithKline
- | Ocaliva (obeticholic acid) / Intercept
Journal: Obeticholic acid differentially regulates hepatic injury and inflammation at different stages of D-galactosamine/lipopolysaccharide-evoked acute liver failure. (Pubmed Central) - Aug 8, 2019
By contrast, OCA suppressed hepatic anti-inflammatory cytokine tgf-β and il-10 at middle stage of GalN/LPS-induced acute liver injury. These results suggest that FXR agonist OCA differentially regulates hepatic injury and inflammation at different stages of GalN/LPS-evoked acute liver failure.
- | tropifexor (LJN452) / Novartis
Journal, Gene Expression Profile: Tropifexor-Mediated Abrogation of Steatohepatitis and Fibrosis Is Associated With the Antioxidative Gene Expression Profile in Rodents. (Pubmed Central) - Aug 8, 2019
Transcriptome analysis of livers from AMLN mice revealed 461 differentially expressed genes following tropifexor treatment that included a combination of signatures associated with reduction of oxidative stress, fibrogenesis, and inflammation. Based on preclinical validation in animal models, tropifexor is a promising investigational therapy that is currently under phase 2 development for NASH.
- Ocaliva (obeticholic acid) / Intercept, azathioprine orodispersible / Generic Mfg.
Primary Biliary Cholangitis With Autoimmune Hepatitis Overlap in Twin Males: A Unique Case of Related Autoimmune Diseases (Exhibit Halls 3 and 4 (Street Level)) - Aug 8, 2019 - Abstract #ACG2019ACG_3026;
Although it is known that PBC and AIH are associated with human leukocyte antigen genes on chromosome 6, further study of the association between these disorders is limited by the paucity of patients. Early diagnosis of this condition is essential to prevent liver related complications with medical management.
- Ocaliva (obeticholic acid) / Intercept
Use of Obeticholic Acid in Patients With Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis (Exhibit Halls 3 and 4 (Street Level)) - Aug 8, 2019 - Abstract #ACG2019ACG_2893;
The mean age of patients was 54 and follow up ranged from 3-12 months. The studies varied with respect to whether OCA was used as monotherapy or added to standard of care (ursodiol).
- Ocaliva (obeticholic acid) / Intercept
The Majority of Patients With Primary Biliary Cholangitits Do Not Achieve the Ideal Treatment Response in a Real World Clinical Practice (Exhibit Halls 3 and 4 (Street Level)) - Aug 8, 2019 - Abstract #ACG2019ACG_1986;
The mean age at the last follow up was 61.8 years (+11.3). 96% were female, 47% were White and 51% were of Hispanic ethnicity.
- Ocaliva (obeticholic acid) / Intercept
Positive Results From REGENERATE: A Phase 3 International, Randomized, Placebo-Controlled Study Evaluating Obeticholic Acid Treatment for NASH (Stars at Night Ballroom - B2) - Aug 8, 2019 - Abstract #ACG2019ACG_277;
Baseline characteristics were well-balanced across groups. Results in Table.
- | Ocaliva (obeticholic acid) / Intercept
Journal: Farnesoid X Receptor Activation by Obeticholic Acid Elevates Liver Low-Density Lipoprotein Receptor Expression by mRNA Stabilization and Reduces Plasma Low-Density Lipoprotein Cholesterol in Mice. (Pubmed Central) - Aug 7, 2019
Furthermore, depletion of HuR in HepG2 cells by short interfering RNA transfection abolished the inducing effect of OCA on LDLR expression. Conclusions- Our study is the first to demonstrate that FXR activation increases LDLR expression in liver tissue by a post-transcriptional regulatory mechanism involving LDLR mRNA-stabilizing factor HuR.
- | bile acid cholic acid (INT-777) / Intercept
Preclinical, Journal: Neuroprotective effects of INT-777 against Aβ-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice. (Pubmed Central) - Aug 3, 2019
Our results indicate that INT-777 has potent neuroprotective effects against Aβ-induced neurotoxicity. Taken together, these findings suggest that the activation of TGR5 could be a novel and promising strategy for the treatment of AD.
- | bile acid cholic acid (INT-777) / Intercept
Journal: Lysophosphatidic acid activates satellite glia cells and Schwann cells. (Pubmed Central) - Aug 1, 2019
Peripheral rat Schwann cells, which are of glial lineage as the satellite glia cells, were also responsive to LPA 18:1. Summarizing, LPA 18:1 primarily activates rather glial cells than neurons, which may subsequently modulate neuronal responsiveness and sensory sensations such as itch and pain.