Panagis Filippakopoulos33
Oleg Fedorov30
Apirat Chaikuad20
Sarah Picaud18
33Panagis Filippakopoulos
30Oleg Fedorov
20Apirat Chaikuad
18Sarah Picaud
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  • Panagis Filippakopoulos, Jun Qi, Sarah Picaud, Yao Shen, William B. Smith, Oleg Fedorov +19 others
  • 2010
Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to(More)
p38α mitogen-activated protein kinase (p38α) is activated by a variety of mechanisms, including autophosphorylation initiated by TGFβ-activated kinase 1 binding protein 1 (TAB1) during myocardial ischemia and other stresses. Chemical-genetic approaches and coexpression in mammalian, bacterial and cell-free systems revealed that mouse p38α(More)
  • Nicholas Kwiatkowski, Nannette Jelluma, Panagis Filippakopoulos, Meera Soundararajan, Michael S. Manak, Mijung Kwon +9 others
  • 2010
Mps1, a dual-specificity kinase, is required for the proper functioning of the spindle assembly checkpoint and for the maintenance of chromosomal stability. As Mps1 function has been implicated in numerous phases of the cell cycle, the development of a potent, selective small-molecule inhibitor of Mps1 should facilitate dissection of Mps1-related biology.(More)
There is a growing recognition of the importance of protein kinases in the control of alternative splicing. To define the underlying regulatory mechanisms, highly selective inhibitors are needed. Here, we report the discovery and characterization of the dichloroindolyl enaminonitrile KH-CB19, a potent and highly specific inhibitor of the CDC2-like kinase(More)
  • Peter Rellos, Ashley C. W. Pike, Frank H. Niesen, Eidarus Salah, Wen Hwa Lee, Frank von Delft +1 other
  • 2010
UNLABELLED Long-term potentiation (LTP), a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM)-dependent kinase II (CaMKII). CaMKII acts as a molecular switch because it(More)
Protein kinase autophosphorylation of activation segment residues is a common regulatory mechanism in phosphorylation-dependent signalling cascades. However, the molecular mechanisms that guarantee specific and efficient phosphorylation of these sites have not been elucidated. Here, we report on three novel and diverse protein kinase structures that reveal(More)
Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multitarget profile has, however, necessitated the application of combination therapies, which can pose major clinical development(More)
  • Cataldo Tarricone, Franco Perrina, Silvia Monzani, Lucia Massimiliano, Myung-Hee Kim, Zygmunt S. Derewenda +3 others
  • 2004
Mutations in the LIS1 gene cause lissencephaly, a human neuronal migration disorder. LIS1 binds dynein and the dynein-associated proteins Nde1 (formerly known as NudE), Ndel1 (formerly known as NUDEL), and CLIP-170, as well as the catalytic alpha dimers of brain cytosolic platelet activating factor acetylhydrolase (PAF-AH). The mechanism coupling the two(More)
By phosphorylating Thr3 of histone H3, Haspin promotes centromeric recruitment of the chromosome passenger complex (CPC) during mitosis. Aurora B kinase, a CPC subunit, sustains chromosome bi-orientation and the spindle assembly checkpoint (SAC). Here, we characterize the small molecule 5-iodotubercidin (5-ITu) as a potent Haspin inhibitor. In vitro, 5-ITu(More)
Protein kinase A (PKA) is a ubiquitous kinase that phos-phorylates a broad variety of substrates. A-kinase anchoring proteins (AKAPs) confer specificity to PKA signaling by tethering the kinase to distinct cellular compartments, thereby limiting the access of PKA to a defined pool of its substrates. [1] Interactions between AKAPs and PKA play key roles in a(More)