Trends in kinase drug discovery: targets, indications and inhibitor design

MM Attwood, D Fabbro, AV Sokolov, S Knapp… - Nature Reviews Drug …, 2021 - nature.com
The FDA approval of imatinib in 2001 was a breakthrough in molecularly targeted cancer
therapy and heralded the emergence of kinase inhibitors as a key drug class in the oncology …

PDK1: At the crossroad of cancer signaling pathways

PA Gagliardi, A Puliafito, L Primo - Seminars in cancer biology, 2018 - Elsevier
Rational target therapy of cancer would benefit from the identification of new targets that can
be easily inhibited by small molecules. An increasing amount of evidence hints at 3 …

Allosteric modulator discovery: from serendipity to structure-based design

S Lu, X He, D Ni, J Zhang - Journal of medicinal chemistry, 2019 - ACS Publications
Allosteric modulators bound to structurally diverse allosteric sites can achieve better
pharmacological advantages than orthosteric ligands. The discovery of allosteric …

Allosteric small-molecule kinase inhibitors

P Wu, MH Clausen, TE Nielsen - Pharmacology & therapeutics, 2015 - Elsevier
Small-molecule kinase inhibitors are invaluable targeted therapeutics for the treatment of
various human diseases, especially cancers. While the majority of approved and developed …

Akt kinase activation mechanisms revealed using protein semisynthesis

N Chu, AL Salguero, AZ Liu, Z Chen, DR Dempsey… - Cell, 2018 - cell.com
Akt is a critical protein kinase that drives cancer proliferation, modulates metabolism, and is
activated by C-terminal phosphorylation. The current structural model for Akt activation by C …

Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation

A Levina, KD Fleming, JE Burke, TA Leonard - Nature communications, 2022 - nature.com
phosphoinositide-dependent kinase 1 (PDK1) is an essential serine/threonine protein
kinase, which plays a crucial role in cell growth and proliferation. It is often referred to as a …

AGC kinases, mechanisms of regulation‎ and innovative drug development

AE Leroux, JO Schulze, RM Biondi - Seminars in cancer biology, 2018 - Elsevier
The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein
kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG …

Non-kinase targets of protein kinase inhibitors

L Munoz - Nature Reviews Drug Discovery, 2017 - nature.com
Kinome-wide profiling platforms have comprehensively identified the relevant kinases that
are targeted by numerous protein kinase inhibitors. However, recent projects have begun to …

A therapeutic approach to pantothenate kinase associated neurodegeneration

LK Sharma, C Subramanian, MK Yun, MW Frank… - Nature …, 2018 - nature.com
Pantothenate kinase (PANK) is a metabolic enzyme that regulates cellular coenzyme A
(CoA) levels. There are three human PANK genes, and inactivating mutations in PANK2 …

Peptide-to-small molecule: a pharmacophore-guided small molecule lead generation strategy from high-affinity macrocyclic peptides

S Yoshida, S Uehara, N Kondo… - Journal of Medicinal …, 2022 - ACS Publications
Recent technological innovations have led to the development of methods for the rapid
identification of high-affinity macrocyclic peptides for a wide range of targets; however, it is …