Home
Resources
Publications
Selective Targeting of Bromodomains of the Bromodomain-PHD Fingers Family Impairs Osteoclast Differentiation

Selective Targeting of Bromodomains of the Bromodomain-PHD Fingers Family Impairs Osteoclast Differentiation

Julia C Meier, Cynthia Tallant, Oleg Fedorov, Hanna Witwicka, Sung-Yong Hwang, Ruud G van Stiphout, Jean-Philippe Lambert, Catherine Rogers, Clarence Yapp, Brian S Gerstenberger, Vita Fedele, Pavel Savitsky, etc.

ACS Chem Biol. 2017 Oct 20;12(10):2619-2630.

PMID: 28849908

Abstract:

Histone acetyltransferases of the MYST family are recruited to chromatin by BRPF scaffolding proteins. We explored functional consequences and the therapeutic potential of inhibitors targeting acetyl-lysine dependent protein interaction domains (bromodomains) present in BRPF1-3 in bone maintenance. We report three potent and selective inhibitors: one (PFI-4) with high selectivity for the BRPF1B isoform and two pan-BRPF bromodomain inhibitors (OF-1, NI-57). The developed inhibitors displaced BRPF bromodomains from chromatin and did not inhibit cell growth and proliferation. Intriguingly, the inhibitors impaired RANKL-induced differentiation of primary murine bone marrow cells and human primary monocytes into bone resorbing osteoclasts by specifically repressing transcriptional programs required for osteoclastogenesis. The data suggest a key role of BRPF in regulating gene expression during osteoclastogenesis, and the excellent druggability of these bromodomains may lead to new treatment strategies for patients suffering from bone loss or osteolytic malignant bone lesions.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP900305375	PFI-4		900305-37-5	Price
IAR4244323	NI-57			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: