Conformationally Defined Rexinoids and Their Efficacy in the Prevention of Mammary Cancers

Journal of Medicinal Chemistry
Venkatram R AtigaddaDonald D Muccio

Abstract

(2E,4E,6Z,8Z)-8-(3',4'-Dihydro-1'(2H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid (UAB30) is currently undergoing clinical evaluation as a novel cancer prevention agent. In efforts to develop even more highly potent rexinoids that prevent breast cancer without toxicity, we further explore here the structure-activity relationship of two separate classes of rexinoids. UAB30 belongs to the class II rexinoids and possesses a 9Z-tetraenoic acid chain bonded to a tetralone ring, whereas the class I rexinoids contain the same 9Z-tetraenoic acid chain bonded to a disubstituted cyclohexenyl ring. Among the 12 class I and class II rexinoids evaluated, the class I rexinoid 11 is most effective in preventing breast cancers in an in vivo rat model alone or in combination with tamoxifen. Rexinoid 11 also reduces the size of established tumors and exhibits a therapeutic effect. However, 11 induces hypertriglyceridemia at its effective dose. On the other hand rexinoid 10 does not increase triglyceride levels while being effective in the in vivo chemoprevention assay. X-ray studies of four rexinoids bound to the ligand binding domain of the retinoid X receptor reveal key structural aspects that enhance potency as well as those...Continue Reading

References

Feb 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·V A MillerR P Warrell
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
May 13, 1999·Bioinformatics·V SobolevM Edelman
Feb 7, 2009·Cancer Biology & Therapy·Wen JiangSusan M Lobo-Ruppert
Aug 1, 2009·The American Journal of Pathology·Daniela BonofiglioSebastiano Andò
May 1, 2013·Journal of Lipid Research·Natalia Y Kedishvili
Sep 27, 2013·Frontiers in Oncology·Petra den HollanderPowel H Brown
Nov 5, 2013·The Journal of Biological Chemistry·Leeann J BoermaMatthew B Renfrow
Mar 8, 2014·Journal of Cellular Physiology·Alessio PapiMassimiliano Bonafé
May 8, 2014·Journal of Medicinal Chemistry·Venkatram R AtigaddaDonald D Muccio
Jul 1, 2015·Canadian Journal of Public Health = Revue Canadienne De Santé Publique·Dessalegn Y MelesseRobert B Tate

❮ Previous
Next ❯

Citations

Mar 30, 2016·World Journal of Stem Cells·Alessio Papi, Marina Orlandi
Oct 11, 2017·Expert Opinion on Therapeutic Patents·Haider BehbehaniThoraya A Farghaly
Apr 4, 2019·Medicinal Research Reviews·Nathalia Rodrigues de Almeida, Martin Conda-Sheridan
Jul 13, 2019·Expert Opinion on Therapeutic Patents·Simone Schierle, Daniel Merk
Mar 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Luz E Tavera-MendozaMyles Brown
Feb 14, 2016·Molecular Cancer Therapeutics·Alicia M WatersElizabeth A Beierle

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.