ATAD2 in cancer : a pharmacologically challenging but tractable target

• Introduction: ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2’s bromodomain (BRD) may be a very challenging task. ATAD2’s BRD has been predicted as a ‘difficult to drug’ or ‘least druggable’ target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding. Areas covered: In this review, after shedding light on the multifaceted roles of ATAD2 in normal physiology as well as in cancer-etiology, we discuss technical challenges rendered by ATAD2’s BRD active site and the recent drug discovery efforts to find small molecule inhibitors against it. Expert opinion: The identification of a novel low-nanomolar semi-permeable chemical probe against ATAD2’s BRD by recent drug discovery campaign has demonstrated it to be a pharmacologically tractable target. Nevertheless, the development of high quality bioavailable inhibitors against ATAD2 is still a pending task. Moreover, ATAD2 may also potentially be utilized as a promising target for future development of RNAi-based therapy to treat cancers. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

AAA ATPase

ATAD2

BRD

cancer

druggable

ligandability

metastasis

siRNA

adenosine triphosphatase

antineoplastic agent

gsk 8814

molecular marker

protein ATAD2

small interfering RNA

unclassified drug

AAA protein

ATAD2 protein

human

DNA binding protein

apoptosis

breast cancer

cancer growth

carcinogenesis

cell cycle arrest

cell proliferation

cell survival

colorectal cancer

drug protein binding

drug structure

drug targeting

endometrium cancer

endometrium tumor

gene overexpression

human

ligand binding

liver cell carcinoma

lung cancer

malignant neoplasm

molecular dynamics

nonhuman

ovary cancer

physiological process

protein domain

protein expression

protein function

proto oncogene

Review

RNA interference

stomach cancer

transcription regulation

tumor cell

uterine cervix cancer

animal

antagonists and inhibitors

drug design

drug development

genetics

metabolism

molecularly targeted therapy

neoplasm

pathology

procedures

Animals

Antineoplastic Agents

ATPases Associated with Diverse Cellular Activities

DNA-Binding Proteins

Drug Discovery

Humans

Molecular Targeted Therapy

Neoplasms

RNA

Small Interfering

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