Jaeho Lee

Efficient Flexible Organic/Inorganic Hybrid Perovskite Light‐Emitting Diodes Based on Graphene Anode

Highly efficient organic/inorganic hybrid perovskite light-emitting diodes (PeLEDs) based on graphene anode are developed for the first time. Chemically inert graphene avoids quenching of excitons by diffused metal atom species from indium tin oxide. The flexible PeLEDs with graphene anode on plastic substrate show good bending stability; they provide an alternative and reliable flexible electrode for highly efficient flexible PeLEDs.

TY.secureWS: An integrated web service security solution based on java

In this paper we propose an integrated XML web service security solution based on Java. The goal of the proposed solution is guaranteeing confidentiality, integrity, and non-repudiation in using web services. It provides flexibility as its security functions are implemented in security handlers instead of modifying web services engine. It also supports extensibility since it has been developed based on international standards such as WS-Security, XKMS, XML Encryption, and XML Signature specifications. The proposed solution provides clients and servers in the business to business environments with confidence and security.

Abstract LB-100: Discovery of HM61713 as an orally available and mutant EGFR selective inhibitor

Introduction: Activating mutations of EGFR are well known as oncogenic driver mutations in lung adenocarcinoma. Currently, EGFR TKIs including Gefitinib and Erlotinib are used as the first line therapy in NSCLC patients harboring EGFR activating mutations. However, drug resistance caused by T790M mutation limits the efficacy of these 1st generation EGFR TKIs. Currently, some of the next generation EGFR TKIs are under investigation for the treatment of lung cancer patients having T790M mutation. In our current presentation, to obtain HM61713, an EGFR mutant selective inhibitor, as a clinical candidate and the evaluation of HM61713 for mutant EGFR cancer model will be introduced. Method: Novel analogues were designed and synthesized to find active compounds for the T790M mutation as well as EGFR activating mutations with good selectivity over wild- type EGFR. Finally, HM61713 was selected as a clinical candidate through multi-optimization processes including both in vitro and in vivo pharmacologcal studies. Results: HM61713 was designed as an irreversible kinase inhibitor having a Michael acceptor, which covalently binds to a cysteine residue near the kinase domain of mutant the EGFR. In a cell wash out test, HM61713 inhibited phospho-EGFR for a long duration with a half-life of over 24 hours. From in vitro study, HM61713 showed potent activities for H1975 (L858-T790M) and HCC827 (exon 19 del.) with GI50 values of 9.2 nM and 10 nM, respectively. Instead, it showed low potency for H358 (wild type EGFR NSCLC) with GI50 of 2,225 nM. In xenograft studies using H1975 and HCC827, HM61713 resulted in good efficacy without showing any side effects. Conclusion: HM61713 showed excellent in vitro and in vivo activities for H1975 harboring L858R-T790M mutation as well as HCC827 having exon 19 deletion mutation with selectivity over wild-type EGFR. Currently, HM61713 is undergoing phase I study (NCT01588145) for NSCLC patients after the failure of 1st generation EGFR TKIs in Korea. Citation Format: Kwang-Ok Lee, Mi Young Cha, Mira Kim, Ji Yeon Song, Jae-Ho Lee, Young Hoon Kim, Young-Mi Lee, Kwee Hyun Suh, Jeewoong Son. Discovery of HM61713 as an orally available and mutant EGFR selective inhibitor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-100. doi:10.1158/1538-7445.AM2014-LB-100

Dual optical role of low-index injection layers for efficient polarizer-free high contrast-ratio organic light-emitting diodes

Polarizer-free high contrast-ratio organic light-emitting diodes (OLEDs) are explored with a structure involving a semi-reflective Cr-based bottom electrode and a dielectric-capped thin Ag top electrode. Their efficiency is shown to be improved significantly with little sacrifice in luminous reflectance by adopting low-refractive-index injection layers that can increase the effective reflectance from the bottom electrode and simultaneously reduce the loss owing to surface plasmon polariton modes. OLEDs employing a low-refractive-index injection layer exhibit improved current efficiency by up to ca. 27.4% than those using index-matched injection layers, with luminous reflectance maintained at as low as 4%.

Abstract LB-256: Optimal clinical dose-finding strategies: Translational preclinical pharmacokineitcs, pharmacodynamics, and efficacy analysis of HM61713, an orally selective EGFR mutant inhibitor

The first-generation of EGFR1 inhibitors (Gefitinib and Erlotinib) has significant clinical benefits in NSCLC caused by activating mutations, but the efficacy of these agents is often limited due to the emergence of drug resistance conferred by a gatekeeper residue, T790M. HM61713 is a third-generation EGFR tyrosine kinase inhibitor that has been evaluated as a novel therapeutic agent for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations. HM61713 is an orally active and a novel EGFR mutant selective inhibitor which is potent on resistance mutation (T790M) without affecting EGFR wild type at efficacious dose level. HM61713 showed an anti-cancer activity in several EGFR mutant lung cancer cell lines including T790M mutation harboring cell line. Integrated pharmacokinetic - pharmacodynamic - xenograft tumor model (PK-PD-XTG) was used to characterize the relationship between HM61713 plasma concentration and tumor growth inhibition (TGI) in H1975 (T790M mutation) xenograft model. Simple one-compartment model applied re-absorption compartment with first-order absorption/elimination was used to describe HM61713 plasma concentration-time profiles. Biophase distribution model with baseline inhibition E max equation was applied to characterize the PD marker (p-EGFR) and tumor volume shrinkage was explained by michaelis-menten kinetics of p-EGFR. Estimated in vivo IC 50 value of p-EGFR inhibition (%) based on plasma free concentration in xenograft mice was 1.14 ng/mL. The human PD marker response curve and the tumor growth inhibition plot were obtained by replacing the mice PK to human PK in our developed model based on the hypothesis thattranslation providesa good relationship of surrogate mice tumor PD to human tumor regression corresponding human PK. According to our simulated curves, we predicted appropriate human active dose from 300 to 800 mg/man and it would be an efficacious dose in patients with NSCLC harboring the EGFR activating and also with T790M resistant mutation. Currently, HM61713 is undergoing in clinical trial phase I/II in NSCLC (ClinicalTrials.gov, NCT01588145). Citation Format: Jooyun Byun, Taehun Song, Donghyun Kim, Junhyeng Son, Kwang-Ok Lee, Jaeho Lee, Yong Hoon Kim, Young-Mi Lee, Kwee Hyun Suh. Optimal clinical dose-finding strategies: Translational preclinical pharmacokineitcs, pharmacodynamics, and efficacy analysis of HM61713, an orally selective EGFR mutant inhibitor. [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 LB-256. doi:10.1158/1538-7445.AM2015-LB-256

Temperature-Controlled Direct Imprinting of Ag Ionic Ink: Flexible Metal Grid Transparent Conductors with Enhanced Electromechanical Durability

Next-generation transparent conductors (TCs) require excellent electromechanical durability under mechanical deformations as well as high electrical conductivity and transparency. Here we introduce a method for the fabrication of highly conductive, low-porosity, flexible metal grid TCs via temperature-controlled direct imprinting (TCDI) of Ag ionic ink. The TCDI technique based on two-step heating is capable of not only stably capturing the Ag ionic ink, but also reducing the porosity of thermally decomposed Ag nanoparticle structures by eliminating large amounts of organic complexes. The porosity reduction of metal grid TCs on a glass substrate leads to a significant decrease of the sheet resistance from 21.5 to 5.5 Ω sq−1 with an optical transmittance of 91% at λu2009=u2009550u2009nm. The low-porosity metal grid TCs are effectively embedded to uniform, thin and transparent polymer films with negligible resistance changes from the glass substrate having strong interfacial fracture energy (~8.2u2009Ju2009m−2). Finally, as the porosity decreases, the flexible metal grid TCs show a significantly enhanced electromechanical durability under bending stresses. Organic light‐emitting diodes based on the flexible metal grid TCs as anode electrodes are demonstrated.

Efficient Solid-State Photoluminescence of Graphene Quantum Dots Embedded in Boron Oxynitride for AC-Electroluminescent Device

Emerging graphene quantum dots (GQDs) have received much attention for use as next-generation light-emitting diodes. However, in the solid-state, π-interaction-induced aggregation-caused photoluminescence (PL) quenching (ACQ) in GQDs makes it challenging to realize high-performance devices. Herein, GQDs incorporated with boron oxynitride (GQD@BNO) are prepared from a mixture of GQDs, boric acid, and urea in water via one-step microwave heating. Due to the effective dispersion in the BNO matrix, ACQ is significantly suppressed, resulting in high PL quantum yields (PL-QYs) of up to 36.4%, eightfold higher than that of pristine GQD in water. The PL-QY enhancement results from an increase in the spontaneous emission rate of GQDs due to the surrounding BNO matrix, which provides a high-refractive-index material and fluorescence energy transfer from the larger-gap BNO donor to the smaller-gap GQD acceptor. A high solid-state PL-QY makes the GQD@BNO an ideal active material for use in AC powder electroluminescent (ACPEL) devices, with the luminance of the first working GQD-based ACPEL device exceeding 283 cd m-2 . This successful demonstration shows promise for the use of GQDs in the field of low-cost, ecofriendly electroluminescent devices.

Highly Flexible & Efficient Organic Light Emitting Diodes with Conventional Transparent Conductive oxides and Ultrathin Plastic Films

Highly flexible and efficient OLEDs is demonstrated on 6μm polymer thin film with conventional TCO electrodes. The devices exhibit stable performance after 1,000 bending even at the bending radius as small as 300 μm

Abstract 2607: Antitumor activity of the selective RAF inhibitor HM95573 in solid tumors and hematologic malignancies

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, NRAS and KRAS is considered one of the causes of solid tumors (NSCLC, CRC,HCC, andthyroid cancers) and hematologic malignancies. 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 BRAFmutation CRC cell lines (e.g. IC50: 118nM for Colo-205) and thyroid cancer cell lines (43nM for B-CPAP); KRAS mutation NSCLC cell lines(297nM for Calu-6),CRC cell lines(65nM for HCT-116) and thyroid cancer cell lines(479nM for CAL-62); and NRAS mutation HCC cell lines(28nM for HepG2) andleukemia cell lines (39nM for HL-60). HM95573 effectively inhibited the phosphorylations of MEK and ERK, downstream kinases associated with cell proliferation in tumor cell lines mutated in BRAF, KRAS and NRAS. In addition, the phosphorylation of downstream kinases of RAF such as MEK and ERK was effectively inhibited with treatment of HM95573 in mutant KRAS NSCLC and CRC cells. HM95573 showed the excellent antitumor activity in mouse models xenografted with BRAF mutation cell line (Colo-205), KRAS mutation cell lines (Calu-6 and HCT-116)and NRAS mutation cell line (HepG2)two RAF inhibitors approved in melanoma which were effective to only BRAF mutation cell lines under conditions tested. The in vivo antitumor activity of HM95573 was potentiated with MEK inhibitors. Now, HM95573 is currently in phase I development in patients with advanced solid tumors including KRAS mutation NSCLC in Korea. Citation Format: Young-Mi Lee, InHwan Bae, Namgoong Gwang Mo, Jae Ho Lee, Suhyeon Kim, Ji Yeon Song, Kyu Hang Lee, Tae Hun Song, Young Gil Ahn, Young Hoon Kim, Kwee Hyun Suh. Antitumor activity of the selective RAF inhibitor HM95573 in solid tumors and hematologic malignancies. [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 2607. doi:10.1158/1538-7445.AM2015-2607

Abstract 2606: Antitumor activity of the selective RAF inhibitor HM95573 in melanoma

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAnnThe 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.nnHM95573 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).nnHM95573 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.nnHM95573 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.nnNow, HM95573 is currently in phase I development in patients with advanced solid tumors including melanoma in Korea.nnCitation 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