Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors

Molecular Cancer Therapeutics
Jun GuoKeith B Glaser

Abstract

The properties of several multitargeted receptor tyrosine kinase inhibitors have been studied for their inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling. A structurally novel, multitargeted tyrosine kinase inhibitor (ABT-869), imatinib (STI571), and four compounds currently in clinical development (AG013736, BAY 43-9006, CHIR258, and SU11248) were tested for inhibition of CSF-1R signaling in both the enzymatic and cellular assays. ABT-869 showed potent CSF-1R inhibition in both the enzyme and cell-based assays (IC50s < 20 nmol/L). In contrast to a previous report, we have found that imatinib has activity against human CSF-1R in both assays at submicromolar concentrations. In enzyme assays, we have found that the inhibition of CSF-1R by both ABT-869 and imatinib are competitive with ATP, with Ki values of 3 and 120 nmol/L, respectively. SU11248 is a potent inhibitor of CSF-1R in the enzyme assay (IC50 = 7 nmol/L) and inhibits receptor phosphorylation in the cellular assay (IC50 = 61 nmol/L). AG013736 was also a potent inhibitor of CSF-1R in both assays (enzyme, IC50 = 16 nmol/L; cellular, IC50 = 21 nmol/L), whereas BAY 43-9006 is less potent in the enzyme assay (IC50 = 107 nmol/L) than in the cellular system...Continue Reading

References

Jul 1, 1992·Immunology Today·A MantovaniL Ruco
Feb 1, 1995·Annals of Medicine·B M Kacinski
Mar 21, 2001·The Journal of Experimental Medicine·E Y LinJ W Pollard
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
May 18, 2001·Nature·L A Liotta, E C Kohn
Oct 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Hisamitsu IdeOwen N Witte
May 18, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sang Hoon LeeCarla Heise
Oct 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·James G ConwayJeff T Hutchins
May 2, 2006·Molecular Cancer Therapeutics·Daniel H AlbertSteven K Davidsen

❮ Previous
Next ❯

Citations

Nov 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cédric LouvetJeffrey A Bluestone
Nov 23, 2006·Assay and Drug Development Technologies·Anne-Marie de Raemy-SchenkKaren Yeow
May 18, 2011·Current Opinion in Oncology·Vinod RaviValerae O Lewis
Aug 1, 2009·Journal of Hematology & Oncology·Jianbiao ZhouChien-Shing Chen
Jan 6, 2011·Expert Opinion on Therapeutic Patents·Christopher J Burns, Andrew F Wilks
Nov 16, 2006·Expert Opinion on Therapeutic Targets·Sofia BakaGordon C Jayson
Dec 13, 2006·Expert Opinion on Investigational Drugs·Alex KiselyovSergey E Tkachenko
May 21, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Eng-Huat TanRoss A Soo
Mar 21, 2007·Cancer Treatment Reviews·M Dror Michaelson
Mar 22, 2012·Medicinal Research Reviews·Mohammed I El-GamalChang-Hyun Oh
Dec 14, 2011·Clinical & Developmental Immunology·Marc BaayFilip Lardon
Feb 19, 2014·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Jun MutoYoshihiko Maehara
Jul 17, 2013·Expert Opinion on Therapeutic Targets·Liu HongLubi Brain
Nov 6, 2009·Blood·Kate VandykeAndrew C W Zannettino
Jan 9, 2009·Bioorganic & Medicinal Chemistry Letters·Christopher J BurnsAndrew F Wilks
Jun 23, 2018·Current Medicinal Chemistry·Eunae Kim, Cheolhee Kim
Jun 20, 2019·Current Medicinal Chemistry·Qiuju XunXiaoyun Lu
Oct 29, 2020·Expert Opinion on Therapeutic Patents·William A Denny, Jack U Flanagan
May 2, 2006·Molecular Cancer Therapeutics·Daniel H AlbertSteven K Davidsen
Dec 24, 2010·Molecular Cancer Therapeutics·Graham C FletcherMark R Bray
Apr 22, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Archana KumariRajesh K Singh

❮ 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.