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Perturbation-Based Proteomic Correlation Profiling as a Target Deconvolution Methodology.
Cell Chem Biol. 2019 01 17; 26(1):137-143.e8.CC

Abstract

Molecular target identification of small molecules, so-called target deconvolution, is a major obstacle to phenotype-based drug discovery. Here, we developed an approach called perturbation-based proteomic correlation profiling (PPCP) utilizing the correlation between protein quantity and binding activity of compounds under cellular perturbation by gene silencing and successfully identified lanosterol synthase as a molecular target of TGF-β pathway inhibitor. This PPCP concept was extended to the use of a cell line panel and provides a new option for target deconvolution.

Authors+Show Affiliations

Rare Disease Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.Translational Research Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo 134-8630, Japan.Pain and Neuroscience Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.Biomarker Department, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo 134-8630, Japan.Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo 134-8630, Japan.Modality Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo 134-8630, Japan.Pain and Neuroscience Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.Rare Disease Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.Pain and Neuroscience Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan.Pain and Neuroscience Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan. Electronic address: kobayashi.hideki.gc@daiichisankyo.co.jp.Research Management Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo 134-8630, Japan. Electronic address: kubota.kazuishi.ci@rdn.daiichisankyo.co.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30449674

Citation

Ohki, Yu, et al. "Perturbation-Based Proteomic Correlation Profiling as a Target Deconvolution Methodology." Cell Chemical Biology, vol. 26, no. 1, 2019, pp. 137-143.e8.
Ohki Y, Sakurai H, Hoshino M, et al. Perturbation-Based Proteomic Correlation Profiling as a Target Deconvolution Methodology. Cell Chem Biol. 2019;26(1):137-143.e8.
Ohki, Y., Sakurai, H., Hoshino, M., Terashima, H., Shimizu, H., Ishikawa, T., Ogiyama, T., Muramatsu, Y., Nakanishi, T., Miyazaki, S., Tsuruoka, H., Kobayashi, H., & Kubota, K. (2019). Perturbation-Based Proteomic Correlation Profiling as a Target Deconvolution Methodology. Cell Chemical Biology, 26(1), 137-e8. https://doi.org/10.1016/j.chembiol.2018.10.012
Ohki Y, et al. Perturbation-Based Proteomic Correlation Profiling as a Target Deconvolution Methodology. Cell Chem Biol. 2019 01 17;26(1):137-143.e8. PubMed PMID: 30449674.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Perturbation-Based Proteomic Correlation Profiling as a Target Deconvolution Methodology. AU - Ohki,Yu, AU - Sakurai,Hidetaka, AU - Hoshino,Madoka, AU - Terashima,Hideki, AU - Shimizu,Hiroki, AU - Ishikawa,Tomio, AU - Ogiyama,Tomoko, AU - Muramatsu,Yasunori, AU - Nakanishi,Toshiyuki, AU - Miyazaki,Shojiro, AU - Tsuruoka,Hiroyuki, AU - Kobayashi,Hideki, AU - Kubota,Kazuishi, Y1 - 2018/11/15/ PY - 2018/05/08/received PY - 2018/07/13/revised PY - 2018/10/08/accepted PY - 2018/11/20/pubmed PY - 2019/11/30/medline PY - 2018/11/20/entrez KW - TGF-β pathway inhibitor KW - cell line panel KW - chemical proteomics KW - gene knockdown KW - lanosterol synthase KW - mass spectrometry KW - perturbation-based proteomic correlation profiling KW - phenotype-based drug discovery KW - radioactive compound binding assay KW - target deconvolution SP - 137 EP - 143.e8 JF - Cell chemical biology JO - Cell Chem Biol VL - 26 IS - 1 N2 - Molecular target identification of small molecules, so-called target deconvolution, is a major obstacle to phenotype-based drug discovery. Here, we developed an approach called perturbation-based proteomic correlation profiling (PPCP) utilizing the correlation between protein quantity and binding activity of compounds under cellular perturbation by gene silencing and successfully identified lanosterol synthase as a molecular target of TGF-β pathway inhibitor. This PPCP concept was extended to the use of a cell line panel and provides a new option for target deconvolution. SN - 2451-9448 UR - https://www.unboundmedicine.com/medline/citation/30449674/Perturbation_Based_Proteomic_Correlation_Profiling_as_a_Target_Deconvolution_Methodology_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2451-9456(18)30345-3 DB - PRIME DP - Unbound Medicine ER -