2023
article
OpenAlex
Daiki Takahashi, Taiichi Ora, Shigekazu Sasaki, Naoki Ishii et autres
Targeted protein degradation via the ubiquitin-proteasome system has emerged as one of the most promising drug discovery modalities. Autophagy, another intracellular degradation system, can target a wide range of nonproteinous substrates as well as proteins, but its application to targeted degradation is …
jp
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Accès ouvert
2020
erratum
OpenAlex
Magdalena M. Szewczyk, Yoshinori Ishikawa, Shawna Leslie Organ, Nozomu Sakai et autres
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ca, jp, lt
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Accès ouvert
2020
article
OpenAlex
Magdalena M. Szewczyk, Yoshinori Ishikawa, Shawna Leslie Organ, Nozomu Sakai et autres
Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in …
ca, jp, lt
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Accès ouvert
2018
preprint
OpenAlex
Magdalena M. Szewczyk, Yoshinori Ishikawa, Shawna Leslie Organ, Nozomu Sakai et autres
Abstract Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective and cell active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, …
ca, jp, lt
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Accès ouvert
2018
article
OpenAlex
Nobumichi Ohoka, Osamu Ujikawa, Kenichiro Shimokawa, Tomoya Sameshima et autres
Targeted protein degradation by small molecules is an emerging modality with significant potential for drug discovery. We previously developed chimeric molecules, termed specific and non-genetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs), which induce the ubiquitylation and proteasomal degradation of target …
us, jp
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Accès ouvert
2018
article
OpenAlex
Norihito Shibata, Kenichiro Shimokawa, Katsunori Nagai, Nobumichi Ohoka et autres
Chronic myelogenous leukemia (CML) is characterized by the oncogenic fusion protein, BCR-ABL protein kinase, against which clinically useful inhibitors have been developed. An alternative approach to treat CML is to degrade the BCR-ABL protein. Recently, potent degraders against BCR-ABL have been developed …
jp
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Accès ouvert
2018
article
OpenAlex
Nobumichi Ohoka, Yoko Morita, Katsunori Nagai, Kenichiro Shimokawa et autres
Aberrant expression of proteins often underlies many diseases, including cancer. A recently developed approach in drug development is small molecule-mediated, selective degradation of dysregulated proteins. We have devised a protein-knockdown system that utilizes chimeric molecules termed specific and nongenetic IAP-dependent protein erasers …
us, jp
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Accès ouvert
2017
article
OpenAlex
Kenichiro Shimokawa, Norihito Shibata, Tomoya Sameshima, Naoki Miyamoto et autres
Protein degradation technology based on hybrid small molecules is an emerging drug modality that has significant potential in drug discovery and as a unique method of post-translational protein knockdown in the field of chemical biology. Here, we report the first example of …
jp
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Accès ouvert
2017
article
OpenAlex
Norihito Shibata, Katsunori Nagai, Yoko Morita, Osamu Ujikawa et autres
Targeted protein degradation using small molecules is a novel strategy for drug development. We have developed hybrid molecules named specific and nongenetic inhibitor of apoptosis protein [IAP]-dependent protein erasers (SNIPERs) that recruit IAP ubiquitin ligases to degrade target proteins. Here, we show …
jp
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Accès ouvert
2017
article
OpenAlex
Norihito Shibata, Naoki Miyamoto, Katsunori Nagai, Kenichiro Shimokawa et autres
Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of …
jp
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Accès ouvert
2017
article
OpenAlex
Nobumichi Ohoka, Katsunori Nagai, Norihito Shibata, Takayuki Hattori et autres
We previously developed a hybrid small molecule SNIPER (Specific and Nongenetic IAP-dependent Protein ERaser) against transforming acidic coiled-coil-3 (TACC3), SNIPER(TACC3), that induces proteasomal degradation of TACC3 protein. In this study, we found that SNIPER(TACC3) induces cytoplasmic vacuolization derived from endoplasmic reticulum (ER) …
jp
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Accès ouvert
2017
article
OpenAlex
Nobumichi Ohoka, Keiichiro Okuhira, Masahiro Ito, Katsunori Nagai et autres
Many diseases, especially cancers, result from aberrant or overexpression of pathogenic proteins. Specific inhibitors against these proteins have shown remarkable therapeutic effects, but these are limited mainly to enzymes. An alternative approach that may have utility in drug development relies on selective …
us, jp, cn
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