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Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer.
TLDR
The usefulness of defective mismatch repair, BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy is investigated and MMR assays identify patients with a low risk of recurrence.
Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer.
TLDR
The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR.
Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections.
TLDR
The ability of T-wave IM spectrometry to differentiate diastereomers differing in Ω(N(2)) value by only 1 Å(2) is demonstrated, even though the resolution of these IM experiments were ∼40 (Ω/ΔΩ).
Metabolism and Disposition of Vilanterol, a Long-Acting β2-Adrenoceptor Agonist for Inhalation Use in Humans
TLDR
This work highlights a number of complexities associated with determining human absorption, distribution, metabolism, and excretion (ADME) for inhaled molecules—mainly related to the low chemical doses and complications associated with the inhalation route of administration.
Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man.
TLDR
The favourable selectivity profile of SRT2104 allows for the use of this SIRT1 modulator for target validation in the clinic, and the food effect can be used to maximize exposure in future clinical studies.
Sites of metabolic substitution: investigating metabolite structures utilising ion mobility and molecular modelling.
TLDR
The UPLC/IMS-MS method demonstrates the ability to measure reproducibly by ion mobility, metabolite structural isomers, which differ in collision cross-section, both theoretical and experimentally derived, by less than 1 Å(2).
Tafenoquine treatment of Plasmodium vivax malaria: suggestive evidence that CYP2D6 reduced metabolism is not associated with relapse in the Phase 2b DETECTIVE trial
TLDR
Preliminary evidence is provided that in CYP2D6 IMs, TQ efficacy in P. vivax-infected individuals is not diminished to the same extent as PQ, but results remain to be confirmed prospectively in the ongoing phase 3 studies.
Evaluation of preparative high performance liquid chromatography and cryoprobe-nuclear magnetic resonance spectroscopy for the early quantitative estimation of drug metabolites in human plasma.
TLDR
A novel approach is described, using preparative high performance liquid chromatography and cryoprobe-nuclear magnetic resonance spectroscopy, to determine the human systemic exposure to a drug and its metabolites using samples derived from Phase I clinical studies.
Evaluation of a chimeric (uPA+/+)/SCID mouse model with a humanized liver for prediction of human metabolism
TLDR
The results of this and other studies suggest that while limitations for prediction of human metabolism and disposition exist, humanized chimeric mouse models can potentially represent informative new tools in drug discovery and development.
Human absorption, distribution, metabolism and excretion properties of drug molecules: a plethora of approaches.
TLDR
Recently developed approaches to identify and quantification of metabolites in samples from classical human PK studies using technologies suitable for non-radiolabelled drug molecules, namely liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy are described.
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