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Aramchol
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Aramchol (arachidyl amido cholanoic acid; Galmed) is a conjugate of cholic acid and arachidic acid, and belongs to the synthetic fatty acid bile acid conjugates (FABACs) family. Aramchol inhibits the liver enzyme stearoyl-CoA desaturase 1 inhibitor (SCD1), and as a result fatty acid synthesis is reduced while fatty acid oxidation is increased. Additionally, Aramchol has hypocholesterolemic effects due to the upregulation of ATP-binding cassette transporter 1 (ABCA1). Ultimately, Aramchol causes incomplete SCD inhibition while also being anti-atherogenic.
July 22, 2019
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VK2809
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VK2809 (Viking Therapeutics) is a thyroid hormone receptor (THR) β-selective agonist which is selective to liver tissue. It is delivered as a prodrug. VK2809 selectively activates the cytochrome P450 isozyme 3A4 (CYP3A4), which is predominantly found in the liver. This allows increased hepatic exposure, which simultaneously reduces systemic exposure to other tissues such as skeletal muscle and the heart.
July 22, 2019
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Cenicriviroc
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Cenicriviroc (Allergan/Takeda) is a potent immunomodulator that blocks the chemokine receptors-2/5 (CCR-2/5). CCR-2/5 have been linked to the inflammatory and fibrogenic pathways in non-alcoholic steatohepatitis (NASH), and by inhibiting CCR-2/5 it is anticipated that cenicriviroc will reduce inflammation and fibrosis.
July 22, 2019
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Cilofexor
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Cilofexor (Gilead), a nonsteroidal FXR agonist, is a ligand-activated nuclear hormone receptor that is a key regulator of bile acid synthesis, conjugation, and excretion. It is abundant in the liver, gallbladder, intestines, and kidney. Stimulation of FXR in the intestine by bile acids or an FXR agonist results in the release of fibroblast growth factor 19 (FGF19).
July 22, 2019
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Emricasan
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Emricasan (Conatus/Novartis) is a small molecule which inhibits pan-caspases. These enzymes are key modulators of apoptosis and inflammation, and chronically elevated apoptosis is often present in liver disease, which leads to the accumulation of apoptotic cells and the release of apoptotic bodies. These end products of apoptosis are engulfed by surrounding tissues which promote disease pathology and inflammation.
July 22, 2019
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Firsocostat
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Firsocostat (Gilead) is an acetyl-CoA carboxylase (ACC) allosteric inhibitor which binds to the biotin carboxylase domain of ACC with high potency and selectivity. Firsocostat inhibits both isoforms (ACC1 and ACC2) of ACC, which results in the reduction of the production of malonyl-CoA carboxylase, therefore reducing a key substrate for fatty acid synthesis. This also reduces the inhibitory effect of malonyl-CoA on the carnitine palmitoyltransferase 1 (CPT-1), which is the rate-limiting step in β-oxidation and leads to an increase in the breakdown of free fatty acids.
July 22, 2019
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Resmetirom
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Resmetirom (Madrigal Pharmaceuticals) is a thyroid hormone receptor (THR) β-selective agonist which selectively targets receptors in the liver. The THR is involved in the regulation of metabolism, cholesterol, and triglycerides, as well as the pathological buildup of fat in the liver. The high liver specificity of resmetirom aims to avoid adverse events associated with THR activation outside the liver.
July 22, 2019
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Selonsertib
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Selonsertib (Gilead) is a small molecule that inhibits apoptosis signal-regulating kinase 1 (ASK1). ASK1 has been shown to promote inflammation, apoptosis, and fibrosis in settings of oxidative stress. Non-alcoholic steatohepatitis (NASH) increases oxidative stress and ASK1 activation, so by inhibiting ASK1, selonsertib has been shown to decrease inflammation and fibrosis in patients with NASH.
July 22, 2019
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Tropifexor
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FXR is a nuclear receptor that regulates bile acid metabolism and signaling. Activation of the receptor inhibits bile acid synthesis from cholesterol via cytochrome P450 7A1 and increases bile acid conjugation, transport, and excretion. This protects the liver from the potentially harmful effects caused during bile acid accumulation. Tropifexor (Novartis/Pfizer) is a novel, highly potent, non-bile acid FXR agonist. It has demonstrated potent activity in rodent Parkinson’s disease models by measuring the induction of FXR target genes in tissues.
July 22, 2019
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leronlimab
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Leronlimab (CytoDyn) is a humanized monoclonal antibody directed against C-C chemokine receptor 5 (CCR5), which is a co-receptor required for the attachment and entry of CCR5-tropic HIV-1 viruses into host cells.
June 28, 2019
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fostemsavir
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Fostemsavir (GSK3684934) (ViiV Healthcare), previously known as BMS-663068, is an oral prodrug of GSK2616713 (formerly BMS-626529). It is an attachment inhibitor which binds to the gp120 protein of HIV to prevent viral attachment to the host CD4+ T cells, which is necessary for entry into host cells.
June 28, 2019
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cabotegravir/rilpivirine
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Cabotegravir is an integrase strand transfer inhibitor analog of Tivicay (dolutegravir; ViiV Healthcare), and rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), branded as Edurant (Johnson & Johnson).
June 28, 2019
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Truvada
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Truvada ([emtricitabine + tenofovir disoproxil fumarate (TDF)]; Gilead/Japan Tobacco) is a once-daily, fixed-dose combination of two of Gilead’s marketed nucleoside reverse transcriptase inhibitors (NRTIs):
June 28, 2019
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Trogarzo
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Trogarzo (ibalizumab; Theratechnologies/TaiMed Biologics) is a recombinant humanized monoclonal antibody approved for the treatment of HIV-1 infection. It targets the HIV-1 post-attachment process by binding one of the domains of the CD-4 protein, which inhibits a conformational change in CD-4 that is necessary to allow entry of HIV into T-cells.
July 28, 2019
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Symtuza
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Symtuza ([darunavir + cobicistat + emtricitabine + tenofovir alafenamide (TAF)]; Johnson & Johnson) is a once-daily single-tablet regimen (STR) combination of the protease inhibitor (PI) Prezista, the two nucleos(t)ide reverse transcriptase inhibitors (NRTIs), Emtriva (emtricitabine; Gilead) and TAF (Gilead), and the boosting agent Tybost (cobicistat; Gilead). Symtuza is the first STR containing a PI.
June 28, 2019
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