Anti-Human EGFR Monoclonal antibody (CABT-L4514) Functional Grade

Mouse Anti-Human EGFR Monoclonal antibody for FuncS

Specifications


Host Species
Mouse
Antibody Isotype
IgG2a
Clone
528
Species Reactivity
Human
Immunogen
Purified EGFR from A431 cells
Conjugate
Functional Grade

Target


Alternative Names
EGFR; epidermal growth factor receptor; ERBB; HER1; mENA; ERBB1

Citations


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References


Beneficial effect of erlotinib and trastuzumab emtansine combination in lung tumors harboring EGFR mutations

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Authors: Kayatani, Hiroe; Ohashi, Kadoaki; Ninomiya, Kiichiro; Makimoto, Go; Nishii, Kazuya; Higo, Hisao; Watanabe, Hiromi; Kano, Hirohisa; Kato, Yuka; Ninomiya, Takashi; Kubo, Toshio; Rai, Kammei; Ichihara, Eiki; Hotta, Katsuyuki; Tabata, Masahiro; Maeda, Yoshinobu; Kiura, Katsuyuki

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is the standard therapy for non-small cell lung cancer (NSCLC) harboring EGFR mutations, but the resistance is inevitable. The drug-tolerant persister cancer cells are thought to be involved in the resistance. We recently reported that HER2 expression had a negative impact on time-to-treatment-failure in patients with EGFR mutant NSCLC. In this study, we hypothesized that HER2 might be a potential target for alternative combination therapy in NSCLC harboring EGFR mutations. In vitro study showed that the level of HER2 expression had no correlation with the sensitivity to EGFR-TKI, erlotinib but showed some correlation with HER2-inhibitor, ado-trastuzumab emtansine (T-DM1) in multiple EGFR-mutant lung cancer cell lines. In addition, HER2 expression was increased in persister cancer cells in 11-18 cell line harboring EGFR L858R or HCC827 cell line harboring EGFR exon 19 deletion after the exposure to erlotinib in vitro and in vivo. The combination of erlotinib and T-DM1 showed a superior inhibitory effect on cell proliferation compared with those of the erlotinib or T-DM1 alone in either 11-18 or HCC827 cells in vitro. The combination therapy also induced a significantly greater inhibitory effect on tumor growth in xenograft model in mice transplanted with either 11-18 or HCC827 cells compared with erlotinib alone or T-DM1 alone. No body weight loss was observed in these mice. These results suggested that the combination therapy with EGFR-TKI and T-DM1 might be a potentially promising strategy for treating lung cancer harboring EGFR mutations. (C) 2020 Elsevier Inc. All rights reserved.

Optimization and Scale-Up of the Continuous Flow Acetylation and Nitration of 4-Fluoro-2-methoxyaniline to Prepare a Key Building Block of Osimertinib

ORGANIC PROCESS RESEARCH & DEVELOPMENT

Authors: Koeckinger, Manuel; Wyler, Benjamin; Aellig, Christof; Roberge, Dominique M.; Hone, Christopher A.; Kappe, C. Oliver

The development of a scalable telescoped continuous flow procedure for the acetylation and nitration of 4-fluoro-2-methoxyaniline is described. A subsequent batch deprotection then affords 4-fluoro-2-methoxy-5-nitroaniline, a key building block in the synthesis of osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is used for the treatment of nonsmall-cell lung carcinomas carrying EGFR-TKI sensitizing and EGFR T790M resistance mutations. The hazards associated with nitration of organic compounds, such as thermal runaway and explosivity of intermediates, make it difficult to scale up nitrations to industrial quantities, particularly within large-scale batch reactors. In this study, we investigated an acetic acid/aqueous nitric acid mixture as a predominantly kinetically controlled nitration regime and a water-free mixture of acetic acid, fuming nitric acid, and fuming sulfuric acid (oleum) as a mass-transfer-limited nitration regime. A modular microreactor platform with in-line temperature measurement was utilized for the nitration. Furthermore, we identified that it was necessary to protect the amine functionality through acetylation to avoid side reactions. The process parameters and equipment configuration were optimized at laboratory scale for the acetylation and nitration to improve the product yield and purity. The two steps could be successfully telescoped, and the laboratory-scale flow process was operated for 80 min to afford the target molecule in 82% isolated yield over two steps, corresponding to a throughput of 25 mmol/h. The developed flow process was then transferred to an industrial partner for commercial implementation and scaled up by the use of higher flow rates and sizing-up of the microreactor platform to pilot scale to afford the product in 83% isolated yield, corresponding to a throughput of 2 mol/h (0.46 kg/h).

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