Bioorganic and Medicinal Chemistry Letters 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.Exploration of macrocyclic peptide binders to the extracellular CRD domain of human receptor tyrosine kinase-like orphan receptor 1 (ROR1)
Bioorg Med Chem Lett. 2023 Dec 12:129589. doi: 10.1016/j.bmcl.2023.129589. Online ahead of print.ABSTRACTElevated levels of receptor tyrosine kinase-like orphan receptor 1 (RORl) expression are observed in multiple hematological and solid tumors, but not in most of the healthy adult tissues, identifying ROR1 as an attractive target for tumor-specific therapy. Herein we will describe the discovery of macrocyclic peptides as binders of the extracellular Cysteine-Rich Domain (CRD) of human ROR1 via mRNA in vitro selection technology using the PDPS platform, followed by exploration of sidechain SAR of parent macrocycle peptide...
Source: Bioorganic and Medicinal Chemistry Letters - December 14, 2023 Category: Chemistry Authors: Jennifer X Qiao Mark R Witmer Ving Lee Tammy C Wang Patrick C Reid Yuki Arioka Glen Farr Melissa Hill-Drzewi Liang Schweizer Aaron Yamniuk Lin Cheng Bozena Abramczyk Martin Corbett Deepa Calambur Nicolas Szapiel Rolf Ryseck Paul Ponath Michael A Poss Perc Source Type: research
Design, Synthesis, and Biological Evaluation of Novel 8-Substituted Quercetin Derivatives Targeting the β‑Catenin/B-Cell Lymphoma 9 Interaction
Bioorg Med Chem Lett. 2023 Dec 12:129591. doi: 10.1016/j.bmcl.2023.129591. Online ahead of print.ABSTRACTThe β-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for aberrantly active Wnt/β-catenin signaling which actively participates in initiating and progressing of many cancers. Herein, we discovered novel 8-substituted quercetin derivatives with potential inhibitory activities targeting β-catenin/BCL9 PPI. Among all the derivatives, compound B4 displayed the most promising PPI inhibitory activity with an IC50 value of 2.25 μM in a competitive fluorescence polarization assay and...
Source: Bioorganic and Medicinal Chemistry Letters - December 14, 2023 Category: Chemistry Authors: Xinyan Peng Li-An Shen Ya Bao Chenglong Liu Qiushi Chen Hao Zhang Jiayi Li Qingwei Zhang Source Type: research
Design and synthesis of cantharidin derivative DCZ5418 as a TRIP13 inhibitor with anti-multiple myeloma activity in vitro and in vivo
Bioorg Med Chem Lett. 2023 Dec 11:129590. doi: 10.1016/j.bmcl.2023.129590. Online ahead of print.ABSTRACTNatural product cantharidin can inhibit multiple myeloma cell growth in vitro, while serious adverse effects limited its clinical application. Therefore, the structural modification of cantharidin is needed. Herein, inspired by the structural similarity of the aliphatic endocyclic moiety in cantharidin and TRIP13 inhibitor DCZ0415, we designed and synthesized DCZ5418 and its nineteen derivatives. The molecular docking study indicated that DCZ5418 had a similar binding mode to TRIP13 protein as DCZ0415 while with a stron...
Source: Bioorganic and Medicinal Chemistry Letters - December 13, 2023 Category: Chemistry Authors: Sanfeng Dong Ke Hu Yulong Shi Guanli Wang Dandan Yu Yitian Zhao Hui Zhang Yingcong Wang Haiguo Sun Zhijian Xu Qi Jia Yiming Li Yingxia Li Bo Li Jumei Shi Weiliang Zhu Source Type: research
Functional evaluation of an electrophilic focused library to identify a covalent inhibitor against intrinsically disordered circadian clock transcription factors
Bioorg Med Chem Lett. 2023 Dec 10:129588. doi: 10.1016/j.bmcl.2023.129588. Online ahead of print.ABSTRACTIn vitro screening of a focused library of compounds containing an electrophilic warhead identified N-chloroacetyl-bis(trifluoromethyl)aniline derivative 15 as a potent inhibitor of BMAL1-CLOCK heterodimer binding to an E-box DNA fragment. Kinetic analysis of thiol-reactivity demonstrated that iodoacetamide and structurally related 20 are significantly more reactive than or equally reactive as 15, respectively, whereas none inhibited BMAL1-CLOCK interaction with the E-box DNA fragment. These results suggest that 15 bind...
Source: Bioorganic and Medicinal Chemistry Letters - December 12, 2023 Category: Chemistry Authors: Kazuya Yamanaka Yoshihisa Inoue Miki Imanishi Junko Ohkanda Source Type: research
Syntheses of the ω-pyridinium-containing very-long-chain ceramides PyrCer(24:1(15Z)) and PyrCer(24:0) and their anticancer activity
In this study, we prepared the ω-PyrCers of Cer(24:1(15Z)) and Cer(24:0), PyrCer(24:1(15Z)) and PyrCer(24:0), respectively. The key in the synthesis is the Wittig reaction to prepare the ω-bromo fatty acid with an appropriate chain length and (Z)-double bond position. Preliminary evaluation of the PyrCer(24:1(15Z)) and PyrCer(24:0) revealed their potential in hepatocellular carcinoma treatment.PMID:38086468 | DOI:10.1016/j.bmcl.2023.129585 (Source: Bioorganic and Medicinal Chemistry Letters)
Source: Bioorganic and Medicinal Chemistry Letters - December 12, 2023 Category: Chemistry Authors: Ju Young Ko Mi-Yeon Kim Ji-Yoon Jeon Jin Yi Jung Yong-Hyun Han Jae Hyun Kim Source Type: research
Functional evaluation of an electrophilic focused library to identify a covalent inhibitor against intrinsically disordered circadian clock transcription factors
Bioorg Med Chem Lett. 2023 Dec 10:129588. doi: 10.1016/j.bmcl.2023.129588. Online ahead of print.ABSTRACTIn vitro screening of a focused library of compounds containing an electrophilic warhead identified N-chloroacetyl-bis(trifluoromethyl)aniline derivative 15 as a potent inhibitor of BMAL1-CLOCK heterodimer binding to an E-box DNA fragment. Kinetic analysis of thiol-reactivity demonstrated that iodoacetamide and structurally related 20 are significantly more reactive than or equally reactive as 15, respectively, whereas none inhibited BMAL1-CLOCK interaction with the E-box DNA fragment. These results suggest that 15 bind...
Source: Bioorganic and Medicinal Chemistry Letters - December 12, 2023 Category: Chemistry Authors: Kazuya Yamanaka Yoshihisa Inoue Miki Imanishi Junko Ohkanda Source Type: research
Syntheses of the ω-pyridinium-containing very-long-chain ceramides PyrCer(24:1(15Z)) and PyrCer(24:0) and their anticancer activity
In this study, we prepared the ω-PyrCers of Cer(24:1(15Z)) and Cer(24:0), PyrCer(24:1(15Z)) and PyrCer(24:0), respectively. The key in the synthesis is the Wittig reaction to prepare the ω-bromo fatty acid with an appropriate chain length and (Z)-double bond position. Preliminary evaluation of the PyrCer(24:1(15Z)) and PyrCer(24:0) revealed their potential in hepatocellular carcinoma treatment.PMID:38086468 | DOI:10.1016/j.bmcl.2023.129585 (Source: Bioorganic and Medicinal Chemistry Letters)
Source: Bioorganic and Medicinal Chemistry Letters - December 12, 2023 Category: Chemistry Authors: Ju Young Ko Mi-Yeon Kim Ji-Yoon Jeon Jin Yi Jung Yong-Hyun Han Jae Hyun Kim Source Type: research
Synthesis, activity, and their relationships of 2,4-diaminonicotinamide derivatives as EGFR inhibitors targeting C797S mutation
Bioorg Med Chem Lett. 2023 Dec 6:129575. doi: 10.1016/j.bmcl.2023.129575. Online ahead of print.ABSTRACTThe C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Herein, we describe the discovery of the 2,4-diaminonicotinamide derivative 5j, which shows potent inhibitory activity against EGFR del19/T790M/C797S and L858R/T790M/C797S. We also report the structure-activity relationship of the 2,4-diaminonicotinamide derivatives and the co-crystal structure of 5j and EGFR del19/T790M/C797S.PMID:38065292 | DOI:10.1016/j.bmcl.2023....
Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Hideaki Kageji Takayuki Momose Yasuhito Nagamoto Noriko Togashi Isao Yasumatsu Yosuke Nishikawa Kawori Kihara Kumiko Hiramoto Megumi Minami Naomi Kasanuki Takeshi Isoyama Hiroyuki Naito Source Type: research
Discovery of flavone-derivatives as the new skeleton of transient receptor potential vanilloid 3 channel antagonists
Bioorg Med Chem Lett. 2023 Dec 6:129577. doi: 10.1016/j.bmcl.2023.129577. Online ahead of print.ABSTRACTTransient receptor potential vanilloid 3 (TRPV3) channel is a temperature-sensitive and Ca2+-permeable nonselective cation channel, which is abundantly expressed in skin keratinocyte and plays an important role in skin homeostasis and repair. However, only a few TRPV3 inhibitors were reported. Few selective and potent modulators of the TRPV3 channel have hindered the progress of the investigation and clinical application. TRPV3 channel research still faces challenges and requires the new inhibitors. Flavonoids are a kind...
Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Lili Wang Ling Zhang Rongfeng Liu Yimei Xu Zhifeng Tang Congxiao Zhang Zhongyin Zhang Source Type: research
Synthesis, activity, and their relationships of 2,4-diaminonicotinamide derivatives as EGFR inhibitors targeting C797S mutation
Bioorg Med Chem Lett. 2023 Dec 6:129575. doi: 10.1016/j.bmcl.2023.129575. Online ahead of print.ABSTRACTThe C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Herein, we describe the discovery of the 2,4-diaminonicotinamide derivative 5j, which shows potent inhibitory activity against EGFR del19/T790M/C797S and L858R/T790M/C797S. We also report the structure-activity relationship of the 2,4-diaminonicotinamide derivatives and the co-crystal structure of 5j and EGFR del19/T790M/C797S.PMID:38065292 | DOI:10.1016/j.bmcl.2023....
Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Hideaki Kageji Takayuki Momose Yasuhito Nagamoto Noriko Togashi Isao Yasumatsu Yosuke Nishikawa Kawori Kihara Kumiko Hiramoto Megumi Minami Naomi Kasanuki Takeshi Isoyama Hiroyuki Naito Source Type: research
Discovery of flavone-derivatives as the new skeleton of transient receptor potential vanilloid 3 channel antagonists
Bioorg Med Chem Lett. 2023 Dec 6:129577. doi: 10.1016/j.bmcl.2023.129577. Online ahead of print.ABSTRACTTransient receptor potential vanilloid 3 (TRPV3) channel is a temperature-sensitive and Ca2+-permeable nonselective cation channel, which is abundantly expressed in skin keratinocyte and plays an important role in skin homeostasis and repair. However, only a few TRPV3 inhibitors were reported. Few selective and potent modulators of the TRPV3 channel have hindered the progress of the investigation and clinical application. TRPV3 channel research still faces challenges and requires the new inhibitors. Flavonoids are a kind...
Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Lili Wang Ling Zhang Rongfeng Liu Yimei Xu Zhifeng Tang Congxiao Zhang Zhongyin Zhang Source Type: research
Synthesis, activity, and their relationships of 2,4-diaminonicotinamide derivatives as EGFR inhibitors targeting C797S mutation
Bioorg Med Chem Lett. 2023 Dec 6:129575. doi: 10.1016/j.bmcl.2023.129575. Online ahead of print.ABSTRACTThe C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Herein, we describe the discovery of the 2,4-diaminonicotinamide derivative 5j, which shows potent inhibitory activity against EGFR del19/T790M/C797S and L858R/T790M/C797S. We also report the structure-activity relationship of the 2,4-diaminonicotinamide derivatives and the co-crystal structure of 5j and EGFR del19/T790M/C797S.PMID:38065292 | DOI:10.1016/j.bmcl.2023....
Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Hideaki Kageji Takayuki Momose Yasuhito Nagamoto Noriko Togashi Isao Yasumatsu Yosuke Nishikawa Kawori Kihara Kumiko Hiramoto Megumi Minami Naomi Kasanuki Takeshi Isoyama Hiroyuki Naito Source Type: research
Discovery of flavone-derivatives as the new skeleton of transient receptor potential vanilloid 3 channel antagonists
Bioorg Med Chem Lett. 2023 Dec 6:129577. doi: 10.1016/j.bmcl.2023.129577. Online ahead of print.ABSTRACTTransient receptor potential vanilloid 3 (TRPV3) channel is a temperature-sensitive and Ca2+-permeable nonselective cation channel, which is abundantly expressed in skin keratinocyte and plays an important role in skin homeostasis and repair. However, only a few TRPV3 inhibitors were reported. Few selective and potent modulators of the TRPV3 channel have hindered the progress of the investigation and clinical application. TRPV3 channel research still faces challenges and requires the new inhibitors. Flavonoids are a kind...
Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Lili Wang Ling Zhang Rongfeng Liu Yimei Xu Zhifeng Tang Congxiao Zhang Zhongyin Zhang Source Type: research
Synthesis, activity, and their relationships of 2,4-diaminonicotinamide derivatives as EGFR inhibitors targeting C797S mutation
Bioorg Med Chem Lett. 2023 Dec 6:129575. doi: 10.1016/j.bmcl.2023.129575. Online ahead of print.ABSTRACTThe C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Herein, we describe the discovery of the 2,4-diaminonicotinamide derivative 5j, which shows potent inhibitory activity against EGFR del19/T790M/C797S and L858R/T790M/C797S. We also report the structure-activity relationship of the 2,4-diaminonicotinamide derivatives and the co-crystal structure of 5j and EGFR del19/T790M/C797S.PMID:38065292 | DOI:10.1016/j.bmcl.2023....
Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Hideaki Kageji Takayuki Momose Yasuhito Nagamoto Noriko Togashi Isao Yasumatsu Yosuke Nishikawa Kawori Kihara Kumiko Hiramoto Megumi Minami Naomi Kasanuki Takeshi Isoyama Hiroyuki Naito Source Type: research
Discovery of flavone-derivatives as the new skeleton of transient receptor potential vanilloid 3 channel antagonists
Bioorg Med Chem Lett. 2023 Dec 6:129577. doi: 10.1016/j.bmcl.2023.129577. Online ahead of print.ABSTRACTTransient receptor potential vanilloid 3 (TRPV3) channel is a temperature-sensitive and Ca2+-permeable nonselective cation channel, which is abundantly expressed in skin keratinocyte and plays an important role in skin homeostasis and repair. However, only a few TRPV3 inhibitors were reported. Few selective and potent modulators of the TRPV3 channel have hindered the progress of the investigation and clinical application. TRPV3 channel research still faces challenges and requires the new inhibitors. Flavonoids are a kind...
Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Lili Wang Ling Zhang Rongfeng Liu Yimei Xu Zhifeng Tang Congxiao Zhang Zhongyin Zhang Source Type: research
