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The mitogen-activated protein kinase (MAPK) pathway is particularly important for the survival and proliferation of tumor cells. Activation of the MAPK pathway due to mutations in BRAF and NRAS is considered one of the causes of melanoma. HM95573 is a novel, highly potent RAF kinase inhibitor. Biochemically assayed for over 120 kinases, HM95573 showed the high selectivity toward BRAF mutant and CRAF kinases. The half maximal inhibition concentrations (IC50) of HM95573 against BRAFWT, BRAFV600E and CRAF kinases were 41nM, 7nM and 2nM, respectively. The strongly inhibited kinases subsequent to RAF kinases appeared to be CSF1R (44nM), DDR1 (77nM) and DDR2 (182 nM). HM95573 potently inhibited the growth of mutant BRAF melanoma cell lines such asA375 (IC50: 57nM) and SK-MEL-28 (69nM) and of mutant NRAS melanoma cell lines such asSK-MEL-2 (53nM) and SK-MEL-30 (24nM). In addition, the phosphorylations of MEK and ERK downstream kinases associated with cell proliferation were effectively inhibited with treatment of HM95573in mutant BRAF and mutant NRAS melanoma cells.HM95573inhibited the downstream signaling in melanoma cells even in the presence of HGF which is known to mediate innate resistance to RAF inhibitors. HM95573 showed the excellent antitumor activity in mouse models xenografted with both of BRAF mutation cell lines (e.g. A375 and SK-MEL-28) and NRAS mutation cell lines (such as SK-MEL-2 and SK-MEL-30) compared to two RAF inhibitors approved in melanoma which were effective to only BRAF mutation cell lines under conditions tested. Furthermore, HM95573 did not show a potential to paradoxical activation inducing tumor growth in mouse xenograft study using A431 cuSCC (cutaneous squamous cell carcinoma)cancer cell. Now, HM95573 is currently in phase I development in patients with advanced solid tumors including melanoma in Korea. Citation Format: InHwan Bae, YoungGil Ahn, Namgoong GwangMo, SuHyeon Kim, JiYeon Song, TaeHun Song, JaeHo Lee, KyuHang Lee, Young-Mi Lee, YoungHoon Kim, KweeHyun Suh. Antitumor activity of the selective RAF inhibitor HM95573 in melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2606. doi:10.1158/1538-7445.AM2015-2606

An in situ particle monitor (ISPM) was developed to measure the concentration of several hundred nanosized contaminant particles generated from the semiconductor process. It is difficult to measure particles below 300 nm owing to low sensitivity and reliability. To improve the sensitivity and reduce the uncertainty caused by the Gaussian distribution of laser, a beam homogenizing module was applied to transform the Gaussian beam into a flat-top beam by total internal reflection. The performance of the beam-homogenizing ISPM was evaluated by measuring standard polystyrene latex particles in vacuum. We analyzed the measurement efficiency by a comparative evaluation with a scanning mobility particle sizer. Following this, the count of particles generated from the exhaust line of a plasma-enhanced chemical vapor deposition process was measured for real-time process diagnosis.

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