Patrick J. Rudewicz

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GDC-0449 (2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide) is a potent, selective Hedgehog (Hh) signalling pathway inhibitor being developed for the treatment of various cancers. The in vivo clearance of GDC-0449 was estimated to be 23.0, 4.65, 0.338, and 19.3 ml min(-1) kg(-1) in mouse, rat, dog and monkeys, respectively. The(More)
To support clinical development, a solid phase extraction (SPE) liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for the determination of GDC-0449 concentrations in human plasma has been developed and validated. Samples (200 microl) were extracted using an Oasis MCX 10 mg 96-well SPE plate and the resulting extracts were analyzed using(More)
INO-1001 is a PARP-1 inhibitor that interrupts the repair process of N-methylpurines generated by temozolomide. We evaluated the pharmacokinetics of INO-1001 and determined its safety when used with temozolomide at 200 mg/m(2)/day x 5 days every 4 weeks. We enrolled 12 adult patients, in cohorts of 3-6 patients, into the study. INO-1001 at doses of 100, 200(More)
The compound (S)-1-[(S)-2-cyclohexyl-2-([S]-2-[methylamino]propanamido)acetyl]-N-(4-phenyl-1,2,3-thiadiazol-5-yl)pyrrolidine-2-carboxamide (GDC-0152) is a peptidomimetic small molecule antagonist of inhibitor of apoptosis (IAP) proteins with antitumor activity. The mass balance, pharmacokinetics, tissue distribution and metabolism of GDC-0152 was(More)
New peptaibols, trichokindins I-VII, have been isolated from the fungus Trichoderma harzianum. Their structures were characterized by spectrometric methods. Trichokindins, which are 18-residue peptides containing one to three isovaline residues, were found to induce Ca(2+)-dependent catecholamine secretion from bovine adrenal medullary chromaffin cells.
Using fast atom bombardment (FAB) and tandem mass spectrometry (MS/MS), we examined 12 synthetic N-carbamoylamino acids (CAA) as tert-butyldimethylsilyl (TBDMS) derivatives. In FAB mass spectrometry and FAB MS/MS, spectra of protonated molecules for CAA provide specific cleavages involving the TBDMS carbamoyl moiety. The daughter scan spectrum of the parent(More)
In drug discovery and development, in vitro absorption and metabolism assays along with in vivo pharmacokinetic (PK), pharmacodynamic (PD), and toxicokinetic (TK) studies are used to evaluate a potential drug candidate. More recently, imaging mass spectrometry approaches have been successfully reported to aid in the preclinical assessment of drug(More)
Several modifications of the oxazoline ring of WIN 54954, a broad spectrum antipicornavirus compound, have been prepared in order to address the acid lability and metabolic instability of this compound. We have previously shown that the oxadiazole analogue 3 displayed comparable activity against a variety of rhinoviruses and appeared to be stable to acid. A(More)