SCH 66336 is a trihalo tricyclic compound that is currently undergoing Phase II clinical trials for the treatment of solid tumors. Modifications of SCH 66336 by incorporating such groups as amides, acids, esters, ureas and lactams off the first or the distal piperidine (from the tricycle) provided potent FPT inhibitors some of which exhibited good cellular activity. A number of these compounds incorporate properties that might improve pharmacokinetic stability of these inhibitors by virtue of their increased solubility or by their change in log P.
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Lonafarnib Protects Against Muscle Atrophy Induced by Dexamethasone.
J Cachexia Sarcopenia Muscle
December 2024
Department of Nanobiomedical Science & BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Korea.
Background: Muscle atrophy, including glucocorticoid-induced muscle wasting from treatments such as dexamethasone (DEX), results in significant reductions in muscle mass, strength and function. This study investigates the potential of lonafarnib, a farnesyltransferase inhibitor, to counteract DEX-induced muscle atrophy by targeting key signalling pathways.
Methods: We utilized in vitro models with C2C12 myotubes treated with DEX and in vivo models with Caenorhabditis elegans and DEX-treated Sprague-Dawley rats.
Antiviral therapy for chronic hepatitis delta: new insights from clinical trials and real-life studies.
Gut
December 2024
D-SOLVE consortium, an EU Horizon Europe funded project (No 101057917), Hannover, Germany.
Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, carrying a greater risk of developing cirrhosis and its complications. For decades, pegylated interferon alpha (PegIFN-α) has represented the only therapeutic option, with limited virological response rates and poor tolerability. In 2020, the European Medicines Agency approved bulevirtide (BLV) at 2 mg/day, an entry inhibitor of hepatitis B virus (HBV)/hepatitis delta virus (HDV), which proved to be safe and effective as a monotherapy for up to 144 weeks in clinical trials and real-life studies, including patients with cirrhosis.
View Article and Find Full Text PDFRepurposing of lonafarnib as a treatment for SARS-CoV-2 infection.
JCI Insight
December 2024
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, United States of America.
Article Synopsis
- SARS-CoV-2, the virus responsible for COVID-19, has led to a global pandemic with high death rates, prompting the need for more effective antiviral treatments.
- The study highlights lonafarnib (LNF), an FDA-approved drug, as an effective inhibitor against SARS-CoV-2, working well both alone and in combination with existing antivirals, while also showing effectiveness against various virus variants.
- In tests on humanized mice, LNF demonstrated the ability to reduce viral levels and improve lung health, suggesting it could be a valuable oral treatment option for COVID-19 and possibly other viral infections.
Chronic Hepatitis D Virus Infection and Its Treatment: A Narrative Review.
Microorganisms
October 2024
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Article Synopsis
- * Current treatments, primarily pegylated interferon (PEG-IFN), can suppress HDV but have low cure rates and significant side effects, making their use challenging.
- * New antiviral therapies are being developed that target different stages of HDV replication, showing potential for better long-term treatment results when used alongside PEG-IFN.
The NLRP3 inhibitor Dapansutrile improves the therapeutic action of lonafarnib on progeroid mice.
Aging Cell
September 2024
Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain.
The role of the inflammasomes in aging and progeroid syndromes remain understudied. Recently, MCC950, a NLRP3 inhibitor, was used in Zmpste24 mice to ameliorate the phenotypes. However, the safety of MCC950 was questioned due to liver toxicity observed in humans.
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