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Now showing items 11-20 of 21
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 ...
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, ...
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 ...
A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials.
(ELSEVIER SCI LTD, 2018-11-01)
BACKGROUND: The incidence and clinical significance of electrolyte abnormalities (EAs) in phase I clinical trials are unknown. The objective of this study is to evaluate the incidence and severity of EAs, graded according ...
The kinase polypharmacology landscape of clinical PARP inhibitors.
(NATURE PUBLISHING GROUP, 2020-02-17)
Polypharmacology plays an important role in defining response and adverse effects of drugs. For some mechanisms, experimentally mapping polypharmacology is commonplace, although this is typically done within the same protein ...
Titration of signalling output: insights into clinical combinations of MEK and AKT inhibitors.
(OXFORD UNIV PRESS, 2015-07-01)
BACKGROUND: We aimed to understand the relative contributions of inhibiting MEK and AKT on cell growth to guide combinations of these agents. MATERIALS AND METHODS: A panel of 20 cell lines was exposed to either the MEK ...
First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014.
(AMER ASSOC CANCER RESEARCH, 2015-08-01)
PURPOSE: AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown in vitro and in vivo efficacy across a range of preclinical human cancer models. EXPERIMENTAL DESIGN: A rolling six-dose escalation was performed to ...
Antibody-drug conjugates--an emerging class of cancer treatment.
(NATURE PUBLISHING GROUP, 2016-02-16)
Antibody-drug conjugates (ADCs) are an emerging novel class of anticancer treatment agents that combines the selectivity of targeted treatment with the cytotoxic potency of chemotherapy drugs. New linker technology associated ...
AKT Inhibition in Solid Tumors With AKT1 Mutations.
(AMER SOC CLINICAL ONCOLOGY, 2017-07-10)
Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary ...