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Design and Measurement of Drug Tissue Concentration Asymmetry and Tissue Exposure-Effect (Tissue PK-PD) Evaluation

Autor: Richard Zang, Aline Barth, Harvey Wong, Jan Marik, Jie Shen, Julie Lade, Kerri Grove, Matthew R. Durk, Neil Parrott, Patrick J. Rudewicz, Sylvia Zhao, Tao Wang, Zhengyin Yan, Donglu Zhang

Publikováno v: Journal of Medicinal Chemistry. 65:8713-8734

The "free drug hypothesis" assumes that, in the absence of transporters, the steady state free plasma concentrations equal to that at the site of action that elicit pharmacologic effects. While it is important to utilize the free drug hypothesis, exc

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed020e19b1e50a9215ac6334a3b2b529
https://doi.org/10.1021/acs.jmedchem.2c00502

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Data from RG7204 (PLX4032), a Selective BRAFV600E Inhibitor, Displays Potent Antitumor Activity in Preclinical Melanoma Models

Autor: Fei Su, Gideon Bollag, David Heimbrook, Mary Ellen Simcox, Kathleen Schostack, Joseph F. Grippo, Richard Lee, Sylvia Zhao, Stanley Kolis, Raman Iyer, Zenaida Go, Kathryn Packman, Kenneth Kolinsky, Brian Higgins, Hong Yang

The BRAFV600E mutation is common in several human cancers, especially melanoma. RG7204 (PLX4032) is a small-molecule inhibitor of BRAFV600E kinase activity that is in phase II and phase III clinical testing. Here, we report a preclinical characteriza

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::de9b3ef352a4f9b3dcb4d341d3d7b67c
https://doi.org/10.1158/0008-5472.c.6500097.v1

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Are you laughing with me or at me? Psychopathic traits and the ability to distinguish between affiliation and dominance laughter cues

Autor: Rebecca Waller, Chloe Katz, Rista C. Plate, Natalie Corbett, Grace Daley, Edie Graber, Sylvia Zhao, Katherine All, Craig S. Neumann

Publikováno v: Journal of Personality. 90:631-644

OBJECTIVE Laughter conveys important information that supports social communication and bonding. Research suggests that unique acoustic properties distinguish laughter that promotes affiliation from laughter that conveys dominance, but little is know

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf9140372b07760dbfffcfe452b3982c
https://doi.org/10.1111/jopy.12687

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CLUSTER: A biomarker-integrated targeted therapy study in patients with advanced non-small cell lung cancer

Autor: Qing Zhou, Hua-Jun Chen, Bin-Chao Wang, Zhen Wang, Hai-Yan Tu, Chongrui Xu, Ming-Ying Zheng, Xiao-Yan Bai, Yue-Li Sun, Hong-hong Yan, Bin Gan, Hong Tao, Yingying Wang, Sylvia Zhao, Jin-Ji Yang, Clinton Lai, Yi-Long Wu

PurposeTo better understand the relevance of genomic characteristics of NSCLC for the management of advanced NSCLC in Chinese patients, the phase II CLUSTER umbrella trial simultaneously investigated the efficacy of multiple targeted therapies in Chi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::961432550932505e1897c0abf76a5ecc
https://doi.org/10.21203/rs.3.rs-1359279/v2

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Absorption, Distribution, Metabolism, and Excretion of Capmatinib (INC280) in Healthy Male Volunteers and In Vitro Aldehyde Oxidase Phenotyping of the Major Metabolite

Autor: Regine Hansen, Yi Jin, Kirsten Schroer, Sylvia Zhao, Gian Camenisch, Hubert Borell, Gholamreza Rahmanzadeh, Jan Jaap van Lier, Axel Meissner, Ulrike Pfaar, Ulrike Glaenzel

Publikováno v: Drug Metabolism and Disposition. 48:873-885

Capmatinib (INC280), a highly selective and potent inhibitor of the MET receptor tyrosine kinase, has demonstrated clinically meaningful efficacy and a manageable safety profile in patients with advanced non-small-cell lung cancer harboring MET exon

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b900aac9cb368b3fd41006b6a599782b
https://doi.org/10.1124/dmd.119.090324

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New paradigm for expediting drug development in Asia

Autor: Masaru Hirano, Wataru Honma, Sylvia Zhao, Iris Rajman

Publikováno v: Drug Discovery Today. 25:491-496

Some Asian regulators currently require Phase I data in Asians before joining global Phase II/III trials. Here, we discuss inherent limitations of Phase I ethnic sensitivity studies (ESS) to identify potential interethnic differences. We review recen

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8850a98b329019fb494c3adb14bab24f
https://doi.org/10.1016/j.drudis.2019.12.013

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The first-in-human study of the pan-PIM kinase inhibitor PIM447 in patients with relapsed and/or refractory multiple myeloma

Autor: Shaji Kumar, Carl Simon, Andreas Guenther, Fang Xiang, Sylvia Zhao, K. Gary Vanasse, Enrique M. Ocio, Yeow Tee Goh, Nicolas Hohmann, Sheeba K. Thomas, Marc S. Raab, Moshe Talpaz

Publikováno v: Leukemia. 33:2924-2933

PIM447, a novel pan-PIM inhibitor, has shown preclinical activity in multiple myeloma (MM). In the multicenter, open-label, first-in-human study, patients with relapsed and/or refractory MM were enrolled to determine the maximum-tolerated dose (MTD)

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39fda204c3a0904dce5fef2a52d00811
https://doi.org/10.1038/s41375-019-0482-0

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In Vitro Metabolism by Aldehyde Oxidase Leads to Poor Pharmacokinetic Profile in Rats for c-Met Inhibitor MET401

Autor: Qian Li, Chun Ye Zhang, Yao Chang Xu, Jing Quan Dai, Sylvia Zhao, Jiang Wei Zhang, Feng He, Ji Yue Jeff Zhang, Hui Xin Wan, Hai Bing Deng, Hong Ping Yu, Qian Gang Zheng

Publikováno v: European Journal of Drug Metabolism and Pharmacokinetics. 44:669-680

MET401 is a potent and selective c-Met inhibitor with a novel triazolopyrimidine scaffold. The aim of this study was to determine the pharmacokinetic profile of MET401 in preclinical species, and to identify the metabolic soft spot and enzyme involve

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a6419719abab5c179958c0e4c47f08e4
https://doi.org/10.1007/s13318-019-00557-9

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