The Experts below are selected from a list of 47223 Experts worldwide ranked by ideXlab platform
Kyle A Edgar - One of the best experts on this subject based on the ideXlab platform.
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discovery of 2 3 2 1 isopropyl 3 methyl 1h 1 2 4 triazol 5 yl 5 6 dihydrobenzo f imidazo 1 2 d 1 4 oxazepin 9 yl 1h pyrazol 1 yl 2 methylpropanamide gdc 0032 a β sparing phosphoinositide 3 kinase inhibitor with high unbound exposure and robust in viv
Journal of Medicinal Chemistry, 2013Co-Authors: Chudi Ndubaku, Timothy Heffron, Steven T Staben, Matthew Baumgardner, Nicole Blaquiere, Erin K Bradley, Richard James Bull, Jennafer Dotson, Danette Dudley, Kyle A EdgarAbstract:Dysfunctional signaling through the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway leads to uncontrolled tumor proliferation. In the course of the discovery of novel benzoxepin PI3K inhibitors, we observed a strong dependency of in vivo antitumor activity on the free-Drug exposure. By Lowering the intrinsic clearance, we derived a set of imidazobenzoxazepin compounds that showed improved unbound Drug exposure and effectively suppressed growth of tumors in a mouse xenograft model at Low Drug Dose levels. One of these compounds, GDC-0032 (11l), was progressed to clinical trials and is currently under phase I evaluation as a potential treatment for human malignancies.
Yoon Sung Nam - One of the best experts on this subject based on the ideXlab platform.
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Low power and Low Drug Dose photodynamic chemotherapy via the breakdown of tumor targeted micelles by reactive oxygen species
Journal of Controlled Release, 2018Co-Authors: Geok Leng Seah, Moon Young Yang, Woojin Kim, Jinho Kim, Keunchil Park, Jaewoo Cho, Jee Seon Kim, Yoon Sung NamAbstract:Abstract Tumor-targeted delivery of anticancer agents using nanocarriers has been explored to increase the therapeutic index of cancer chemotherapy. However, only a few nanocarriers are clinically available because the physiological complexity often compromises their ability to target, penetrate, and control the release of Drugs. Here, we report a method which dramatically increases in vivo therapeutic Drug efficacy levels through the photodynamic degradation of tumor-targeted nanocarriers. Folate-decorated poly(ethylene glycol)-polythioketal micelles are prepared to encapsulate paclitaxel and porphyrins. Photo-excitation generates reactive oxygen species within the micelles to cleave the polythioketal backbone efficiently and facilitate Drug release only at the illuminated tumor site. Intravenous injection of a murine xenograft model with a Low Dose of paclitaxel within the micelles, one-milligram Drug per kg (mouse), corresponding to an amount less than that of Taxol by one order of magnitude, induces dramatic tumor regression without any acute systemic inflammation responses or organ toxicity under Low-power irradiation (55 mW cm−2) at 650 nm.
Guangjun Nie - One of the best experts on this subject based on the ideXlab platform.
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triple punch strategy for triple negative breast cancer therapy with minimized Drug dosage and improved antitumor efficacy
ACS Nano, 2015Co-Authors: Yanhua Tian, Yanping Ding, Guangjun NieAbstract:Effective therapeutics against triple negative breast cancer (TNBC), which has no standard-of-care therapy, needs to be developed urgently. Here we demonstrated a strategy of integrating indocyanine green (ICG), paclitaxel (PTX), and survivin siRNA into one thermosensitive poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate)-co-2-(dimethylamino)ethyl methacrylate-b-poly(D,L-lactide-co-glycolide) (P (MEO2MA-co-OEGMA-co-DMAEMA)-b-PLGA) nanoparticle (NP-IPS) for triple-punch strategy against TNBC. The NP-IPS significantly enhanced the stability of ICG. Controlled release of the PTX in tumor regions was triggered by the hyperthermia produced by laser irradiated ICG. The NP-IPS exhibited remarkable antitumor efficacy (almost complete ablation of the tumor xenografts) due to the combinational effects of chemotherapy, photothermal therapy, and gene therapy with Low Drug Dose (ICG, 0.32 μmol/kg; PTX, 0.54 μmol/kg; siRNA, 1.5 mg/kg) and minimal side effects. Taken together, our current study demonstrates a nanoplatform for triple-therapy, which reveals a promising strategy for TNBC treatment.
Chudi Ndubaku - One of the best experts on this subject based on the ideXlab platform.
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discovery of 2 3 2 1 isopropyl 3 methyl 1h 1 2 4 triazol 5 yl 5 6 dihydrobenzo f imidazo 1 2 d 1 4 oxazepin 9 yl 1h pyrazol 1 yl 2 methylpropanamide gdc 0032 a β sparing phosphoinositide 3 kinase inhibitor with high unbound exposure and robust in viv
Journal of Medicinal Chemistry, 2013Co-Authors: Chudi Ndubaku, Timothy Heffron, Steven T Staben, Matthew Baumgardner, Nicole Blaquiere, Erin K Bradley, Richard James Bull, Jennafer Dotson, Danette Dudley, Kyle A EdgarAbstract:Dysfunctional signaling through the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway leads to uncontrolled tumor proliferation. In the course of the discovery of novel benzoxepin PI3K inhibitors, we observed a strong dependency of in vivo antitumor activity on the free-Drug exposure. By Lowering the intrinsic clearance, we derived a set of imidazobenzoxazepin compounds that showed improved unbound Drug exposure and effectively suppressed growth of tumors in a mouse xenograft model at Low Drug Dose levels. One of these compounds, GDC-0032 (11l), was progressed to clinical trials and is currently under phase I evaluation as a potential treatment for human malignancies.
Geok Leng Seah - One of the best experts on this subject based on the ideXlab platform.
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Low power and Low Drug Dose photodynamic chemotherapy via the breakdown of tumor targeted micelles by reactive oxygen species
Journal of Controlled Release, 2018Co-Authors: Geok Leng Seah, Moon Young Yang, Woojin Kim, Jinho Kim, Keunchil Park, Jaewoo Cho, Jee Seon Kim, Yoon Sung NamAbstract:Abstract Tumor-targeted delivery of anticancer agents using nanocarriers has been explored to increase the therapeutic index of cancer chemotherapy. However, only a few nanocarriers are clinically available because the physiological complexity often compromises their ability to target, penetrate, and control the release of Drugs. Here, we report a method which dramatically increases in vivo therapeutic Drug efficacy levels through the photodynamic degradation of tumor-targeted nanocarriers. Folate-decorated poly(ethylene glycol)-polythioketal micelles are prepared to encapsulate paclitaxel and porphyrins. Photo-excitation generates reactive oxygen species within the micelles to cleave the polythioketal backbone efficiently and facilitate Drug release only at the illuminated tumor site. Intravenous injection of a murine xenograft model with a Low Dose of paclitaxel within the micelles, one-milligram Drug per kg (mouse), corresponding to an amount less than that of Taxol by one order of magnitude, induces dramatic tumor regression without any acute systemic inflammation responses or organ toxicity under Low-power irradiation (55 mW cm−2) at 650 nm.
