Targeted Tubulysin B Hydrazide Conjugate for the Treatment of Luteinizing Hormone-Releasing Hormone Receptor-Positive Cancers

Bioconjugate Chemistry
Jyoti RoyPhilip S Low

Abstract

The targeted delivery of chemotherapeutic agents to receptors that are overexpressed on cancer cells has become an attractive strategy to concentrate drugs in cancer cells while avoiding uptake by healthy cells. Luteinizing hormone-releasing hormone receptor (LHRH-R) has attracted considerable interest for this application, since LHRH-R is upregulated in ∼86% of prostate cancers, ∼80% of endometrial cancers, ∼80% of ovarian cancers, and ∼50% of breast cancers, but virtually absent from normal tissues. Although LHRH and related peptides have been used to deliver cytotoxic drugs to LHRH-R overexpressing cancer cells, they have suffered from off-target delivery of the therapeutic agents to the liver and kidneys. To reduce such unwanted uptake by peptide scavenger receptors in the liver and kidneys, we have explored the use of a nonpeptidic LHRH-R antagonist (NBI42902) to construct an LHRH-R targeted tubulysin conjugate (BOEPL-L3-TubBH). In vitro studies with BOEPL-L3-TubBH demonstrate that the conjugate can kill LHRH-R expressing triple-negative breast cancer cells (MDA-MB-231 cells) with low nanomolar IC50. Related studies on tumor-bearing mice further reveal that the same conjugate can eradicate MDA-MB-231 solid tumors without a...Continue Reading

References

Oct 3, 2002·Nature Reviews. Cancer·Theresa M Allen
Jan 23, 2003·Reproductive Biomedicine Online·Claudio Chillik, Aníbal Acosta
Feb 23, 2008·Advances in Experimental Medicine and Biology·S S KakarKyung A Kang
Jul 31, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stephen V LiuJacek Pinski
Dec 21, 2010·European Journal of Nuclear Medicine and Molecular Imaging·Erik VegtOtto C Boerman
Feb 4, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H A AzimM J Piccart
Jul 4, 2012·Prostate Cancer and Prostatic Diseases·N D ShoreP Lange
Jul 11, 2012·Endocrine Reviews·Patrizia LimontaRoberta M Moretti
Nov 17, 2012·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Madita ReutterCarsten Gründker
Nov 21, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lydia W T CheungAlice S T Wong
Aug 21, 2013·Molecular Pharmaceutics·Natalia V NukolovaTatiana K Bronich
Feb 24, 2015·Nature Reviews. Drug Discovery·Madduri SrinivasaraoPhilip S Low
Nov 5, 2016·The Journal of Organic Chemistry·Raffaele ColomboPeter Wipf
Jul 12, 2017·Oncology Letters·Dawei HaoXiaowen Hao
Sep 13, 2017·Chemical Reviews·Madduri Srinivasarao, Philip S Low

❮ Previous
Next ❯

Citations

Aug 17, 2019·Chemistry : a European Journal·Alberto Dal CorsoCesare Gennari
Aug 29, 2021·Pharmaceutics·Mudasir Ahmad BhatArif Tasleem Jan

❮ 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.