One target, different effects: a comparison of distinct therapeutic antibodies against the same targets

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.     

5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion

A variety of benzylidenethiazole analogs have been demonstrated to inhibit 5-lipoxygenase (5-LOX). Here we report the anti-atherogenic potential of 5-(4-hydroxy- 2,3,5-trimethylbenzylidene) thiazolidin-2,4-dione (HMB-TZD), a benzylidenethiazole analog, and its potential mechanism of action in LDL receptor-deficient (Ldlr-/-) mice. HMB-TZD Treatment reduced leukotriene B4 (LTB4) production significantly in RAW264.7 macrophages and SVEC4-10 endothelial cells. Macrophages or endothelial cells pre-incubated with HMB-TZD for 2 h and then stimulated with lipopolysaccharide or tumor necrosis factor-alpha (TNF-α) displayed reduced cytokine production. Also, HMB-TZD reduced cell migration and adhesion in accordance with decreased proinflammatory molecule production in vitro and ex vivo. HMB-TZD treatment of 8-week-old male Ldlr-/- mice resulted in significantly reduced atherosclerotic lesions without a change to plasma lipid profiles. Moreover, aortic expression of pro-atherogenic molecules involved in the recruitment of monocytes to the aortic wall, including TNF-α , MCP-1, and VCAM-1, was downregulated. HMB-TZD also reduced macrophage infiltration into atherosclerotic lesions. In conclusion, HMB-TZD ameliorates atherosclerotic lesion formation possibly by reducing the expression of proinflammatory molecules and monocyte/macrophage recruitment to the lesion. These results suggest that HMB-TZD, and benzylidenethiazole analogs in general, may have therapeutic potential as treatments for atherosclerosis.     

Pressure-enhanced dehydrogenation reaction of the LiBH4-YH3 composite

The increase in hydrogen back pressure unexpectedly enhances the overall dehydrogenation reaction rate of the 4LiBH(4) + YH(3) composite significantly. Also, argon back pressure has a similar influence on the composite. Gas back pressure seems to enhance the dehydrogenation reaction by kinetically suppressing the formation of the diborane by-product.     

Synthesis and characterization of a thiazolo[5,4-d]thiazole-based copolymer for high performance polymer solar cells

A highly processable, new semiconducting polymer, PCDTTz, based on alternating thiazolothiazole and carbazole units was synthesized. The new polymer exhibited a field-effect carrier mobility of up to 3.8 × 10(-3) cm(2) V(-1) s(-1) and bulk heterojunction solar cells made from PCDTTz produced a power conversion efficiency of 4.88% under AM 1.5 G (100 mW cm(-2)) conditions.     

Ionic liquid-assisted carboxylation of amines by CO2: a mechanistic consideration

The catalytic roles of ionic liquids (ILs) in the syntheses of 1,3-disubstituted ureas from the carboxylation of amines by CO(2) were experimentally and theoretically investigated. The carboxylation reaction of n-butylamine was greatly facilitated by the presence of an IL and the catalytic activity of the IL was strongly affected by the nucleophilicity of the anion. Computational study on the mechanistic aspects of the carboxylation with methylamine with or without the presence of an IL, 1-ethyl-3-methylimidazolium chloride, implies that the activation energies of the transition states and the intermediate ionic species could be lowered significantly through the multi-interactions of the carbonyl group of CO(2) with both cations and anions of the ILs.     

Optimized Aluminum Reflector for Enhancement of UVC Cathodoluminescence Based-AlGaN Materials with Carbon Nanotube Field Emitters

The far ultraviolet C (UVC) light sources based on carbon nanotube (CNT) field emitters as excitation sources have become promising light sources for sterilization, disinfection, and water purification. However, the low light extraction efficiency of UVC–CNT light sources still hinders the practical application of these structures. Herein, we report an optimized aluminum (Al) reflector to enhance the light extraction efficiency of UVC–CNT light sources. Optical analysis of UVC-CNT light sources covered by the Al reflectors with various thicknesses ranging from 30 to 150 nm was performed to realize the optimized reflector. The UVC-CNT light sources exhibit the highest light extraction efficiency when the Al reflector layer has an optimized thickness of 100 nm. For comparison, the cathodoluminescence (CL) spectra were recorded for UVC–CNT light sources with and without the optimized Al reflector. The measured light output power and the estimated power efficiency of the UVC–CNT light-source-tube with Al reflector were enhanced by about 27 times over the reference. This enhancement is mainly attributed to the outstanding reflection effect of the Al reflector.     

Phenothiazine‐S,S‐dioxide‐ and fluorene‐based light‐emitting polymers: Introduction of e−‐deficient S,S‐dioxide into e−‐rich phenothiazine

A novel series of poly(10‐hexyl‐phenothiazine‐S,S‐dioxide‐3,7‐diyl) and poly(9,9′‐dioctyl‐fluorene‐2,7‐diyl‐alt‐10‐hexyl‐3,7‐phenothiazine‐S,S‐dioxide) (PFPTZ‐SS) compounds were synthesized through Ni(0)‐mediated Yamamoto polymerization and Pd(II)‐catalyzed Suzuki polymerization. The synthesized polymers were characterized by ¹H NMR spectroscopy and elemental analysis and showed higher glass transition temperatures than that of pristine polyfluorene. In terms of photoluminescence (PL), the PFPTZ‐SS compounds were highly fluorescent with bright blue emissions in the solid state. Light‐emitting devices were fabricated with these polymers in an indium tin oxide/poly(3,4‐ethylene dioxythiophene):poly(styrene sulfonate)/polymer/Ca/Al configuration. The electroluminescence (EL) of the copolymers differed from the PL characteristics: the EL device exhibited a redshifted greenish‐blue emission in contrast to the blue emission observed in the PL. Additionally, this unique phenothiazine‐S,S‐dioxide property, triggered by the introduction of an electron‐deficient SO₂ unit into the electron‐rich phenothiazine, gave rise to improvements in the brightness, maximum luminescence intensity, and quantum efficiency of the EL devices fabricated with PFPTZ‐SS. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1236–1246, 2007     

White electroluminescence from a single polyfluorene containing bis‐DCM units

A series of fluorene‐based copolymers composed of blue‐ and orange‐light‐emitting comonomers were synthesized through palladium‐catalyzed Suzuki coupling reactions. 9,9‐Dihexylfluorene and 2‐(2,6‐bis‐{2‐[1‐(9,9‐dihexyl‐9H‐fluoren‐2‐yl)‐1,2,3,4‐tetrahydroquinolin‐6‐yl]‐vinyl}‐pyran‐4‐ylidene)‐malononitrile (DCMF) were used as the blue‐ and orange‐light‐emitting chromophores, respectively. The resulting single polymers exhibited simultaneous blue (423/450 nm) and orange (580–600 nm) emissions from these two chromophores. By adjusting the fluorene and DCMF contents, white light emission could be obtained from a single polymer; a device with an ITO/PEDOT:PSS/polymer/Ca/Al configuration was found to exhibit pure white electroluminescence with Commission Internationale de L'Eclairage (CIE) coordinates of (0.33, 0.31), a maximum brightness of 1180 cd/m², and a current efficiency of 0.60 cd/A. Furthermore, the white light emission of this device was found to be very stable with respect to variation of the driving voltage. The CIE coordinates of the device were (0.32, 0.29), (0.32, 0.29), and (0.33, 0.31) for driving voltages of 7, 8, and 10 V, respectively. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3380–3390, 2007     

Crystallinity and morphology dependent luminescence of Li-doped Y2−xGdxO3:Eu thin film phosphors

The influence of lithium doping on the crystallization, the surface morphology, and the luminescent properties of pulsed laser deposited Y_2−xGd_xO₃:Eu³⁺ thin film phosphors was investigated. The crystallinity, the surface morphology, and the photoluminescence (PL) of films depended highly on the Li-doping and the Gd content. The relationship between the crystalline and morphological structures and the luminescent properties was studied, and Li⁺ doping was found to effectively enhance not only the crystallinity but also the luminescent brightness of Y_2−xGd_xO₃:Eu³⁺ thin films. In particular, the incorporation of Li and Gd into the Y₂O₃ lattice could induce remarkable increase in the PL. The highest emission intensity was observed Li-doped Y_1.35Gd_0.6O₃:Eu³⁺ thin films whose brightness was increased by a factor of 4.6 in comparison with that of Li-doped Y₂O₃:Eu³⁺ thin films.