Therapeutic Targeting of the General RNA Polymerase II Transcription Machinery

被引：37

作者：

Martin, Ryan D. ^{[1
]}

Hebert, Terence E. ^{[1
]}

Tanny, Jason C. ^{[1
]}

机构：

[1] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 09期

基金：

加拿大健康研究院;

关键词：

RNA polymerase II; transcription; CDK inhibitor; CDK7; CDK9; CDK12; CYCLIN-DEPENDENT KINASE; CONTINUOUS-INFUSION FLAVOPIRIDOL; DINACICLIB SCH 727965; STRUCTURAL BASIS; PHASE-II; P-TEFB; INHIBITOR FLAVOPIRIDOL; IN-VIVO; SELECTIVE INHIBITOR; ANTITUMOR-ACTIVITY;

D O I：

10.3390/ijms21093354

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Inhibitors targeting the general RNA polymerase II (RNAPII) transcription machinery are candidate therapeutics in cancer and other complex diseases. Here, we review the molecular targets and mechanisms of action of these compounds, framing them within the steps of RNAPII transcription. We discuss the effects of transcription inhibitors in vitro and in cellular models (with an emphasis on cancer), as well as their efficacy in preclinical and clinical studies. We also discuss the rationale for inhibiting broadly acting transcriptional regulators or RNAPII itself in complex diseases.

引用

页数：24

共 123 条

[71] Seventy-two hour continuous infusion flavopiridol in relapsed and refractory mantle cell lymphoma [J].

Lin, TS ;

Howard, OM ;

Neuberg, DS ;

Kim, HH ;

Shipp, MA .

LEUKEMIA & LYMPHOMA, 2002, 43 (04) :793-797

[72] TP53 loss creates therapeutic vulnerability in colorectal cancer [J].

Liu, Yunhua ;

Zhang, Xinna ;

Han, Cecil ;

Wan, Guohui ;

Huang, Xingxu ;

Ivan, Cristina ;

Jiang, Dahai ;

Rodriguez-Aguayo, Cristian ;

Lopez-Berestein, Gabriel ;

Rao, Pulivarthi H. ;

Maru, Dipen M. ;

Pahl, Andreas ;

He, Xiaoming ;

Sood, Anil K. ;

Ellis, Lee M. ;

Anderl, Jan ;

Lu, Xiongbin .

NATURE, 2015, 520 (7549) :697-U286

[73] Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs [J].

Loeschmann, Nadine ;

Michaelis, Martin ;

Rothweiler, Florian ;

Zehner, Richard ;

Cinatl, Jaroslav ;

Voges, Yvonne ;

Sharifi, Mohsen ;

Riecken, Kristoffer ;

Meyer, Jochen ;

von Deimling, Andreas ;

Fichtner, Iduna ;

Ghafourian, Taravat ;

Westermann, Frank ;

Cinatl, Jindrich, Jr. .

TRANSLATIONAL ONCOLOGY, 2013, 6 (06) :685-U314

[74] Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin [J].

Lu, HS ;

Chang, DJ ;

Baratte, B ;

Meijer, L ;

Schulze-Gahmen, U .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (03) :737-743

[75] Compensatory induction of MYC expression by sustained CDK9 inhibition via a BRD4-dependent mechanism [J].

Lu, Huasong ;

Xue, Yuhua ;

Yu, Guoying K. ;

Arias, Carolina ;

Lin, Julie ;

Fong, Susan ;

Faure, Michel ;

Weisburd, Ben ;

Ji, Xiaodan ;

Mercier, Alexandre ;

Sutton, James ;

Luo, Kunxin ;

Gao, Zhenhai ;

Zhou, Qiang .

ELIFE, 2015, 4

[76] Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer [J].

Luecking, Ulrich ;

Scholz, Arne ;

Lienau, Philip ;

Siemeister, Gerhard ;

Kosemund, Dirk ;

Bohlmann, Rolf ;

Briem, Hans ;

Terebesi, Ildiko ;

Meyer, Kirstin ;

Prelle, Katja ;

Denner, Karsten ;

Boemer, Ulf ;

Schaefer, Martina ;

Eis, Knut ;

Valencia, Ray ;

Ince, Stuart ;

von Nussbaum, Franz ;

Mumberg, Dominik ;

Ziegelbauer, Karl ;

Klebl, Bert ;

Choidas, Axel ;

Nussbaumer, Peter ;

Baumann, Matthias ;

Schultz-Fademrecht, Carsten ;

Ruehter, Gerd ;

Eickhoff, Jan ;

Brands, Michael .

CHEMMEDCHEM, 2017, 12 (21) :1776-1793

[77] Targeting transcription is no longer a quixotic quest [J].

Mapp, Anna K. ;

Pricer, Rachel ;

Sturlis, Steven .

NATURE CHEMICAL BIOLOGY, 2015, 11 (12) :891-894

[78] PURIFICATION OF P-TEFB, A TRANSCRIPTION FACTOR REQUIRED FOR THE TRANSITION INTO PRODUCTIVE ELONGATION [J].

MARSHALL, NF ;

PRICE, DH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (21) :12335-12338

[79] Structural basis of transcription elongation [J].

Martinez-Rucobo, Fuensanta W. ;

Cramer, Patrick .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2013, 1829 (01) :9-19

[80] In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine) [J].

McClue, SJ ;

Blake, D ;

Clarke, R ;

Cowan, A ;

Cummings, L ;

Fischer, PM ;

MacKenzie, M ;

Melville, J ;

Stewart, K ;

Wang, SD ;

Zhelev, N ;

Zheleva, D ;

Lane, DP .

INTERNATIONAL JOURNAL OF CANCER, 2002, 102 (05) :463-468

← 3 4 5 6 7 8 9 10 11 12 →