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Phase I Trial of the Human Double Minute 2 Inhibitor MK-8242 in Patients With Advanced Solid Tumors.
(AMER SOC CLINICAL ONCOLOGY, 2017-04-20)
Purpose To evaluate MK-8242 in patients with wild-type TP53 advanced solid tumors. Patients and Methods MK-8242 was administered orally twice a day on days 1 to 7 in 21-day cycles. The recommended phase II dose (RP2D) was ...
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
(AMER CHEMICAL SOC, 2016-12-16)
The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, ...
Critical parameters in targeted drug development: the pharmacological audit trail.
(W B SAUNDERS CO-ELSEVIER INC, 2016-08-01)
The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) ...
A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours.
(ELSEVIER SCI LTD, 2016-11-01)
PURPOSE: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, ...
Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.
(NATURE PUBLISHING GROUP, 2017-04-25)
BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which ...
Polypharmacology in Precision Oncology: Current Applications and Future Prospects.
(BENTHAM SCIENCE PUBL LTD, 2017-01-24)
Over the past decade, a more comprehensive, large-scale approach to studying cancer genetics and biology has revealed the challenges of tumor heterogeneity, adaption, evolution and drug resistance, while systems-based ...
Minimizing bias in target selection by exploiting multidisciplinary Big Data and the protein interactome.
(FUTURE SCI LTD, 2016-09-01)
Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors.
(NATL ACAD SCIENCES, 2016-11-29)
Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ...
Combining Molecularly Targeted Agents: Is More Always Better?
(AMER ASSOC CANCER RESEARCH, 2017-03-01)
The concurrent targeting of critical nodes along key signaling pathways with molecularly targeted agents is a rational antitumor strategy, which has had varying degrees of success. Combinatorial challenges include overcoming ...
Maximising the potential of AKT inhibitors as anti-cancer treatments.
(PERGAMON-ELSEVIER SCIENCE LTD, 2017-04-01)
PI3K/AKT signalling is commonly disrupted in human cancers, with AKT being a central component of the pathway, influencing multiple processes that are directly involved in tumourigenesis. Targeting AKT is therefore a highly ...