Targeting EPHA2 with Kinase Inhibitors in Colorectal Cancer
ChemMedChem. 2023 Sep 21:e202300420. doi: 10.1002/cmdc.202300420. Online ahead of print.ABSTRACTThe ephrin type-A 2 receptor tyrosine kinase (EPHA2) is involved in the development and progression of various cancer types, including colorectal cancer (CRC). There is also evidence that EPHA2 plays a key role in the development of resistance to the endothelial growth factor receptor (EGFR) monoclonal antibody Cetuximab used clinically in CRC. Despite the promising pharmacological potential of EPHA2, only a handful of specific inhibitors are currently available. In this concept paper, general strategies for EPHA2 inhibition wit...
Source: ChemMedChem - September 22, 2023 Category: Chemistry Authors: Alix Tr öster Nathalie Jores Konstantin S Mineev Sridhar Sreeramulu Michael DiPrima Giovanna Tosato Harald Schwalbe Source Type: research
Targeting EPHA2 with Kinase Inhibitors in Colorectal Cancer
ChemMedChem. 2023 Sep 21:e202300420. doi: 10.1002/cmdc.202300420. Online ahead of print.ABSTRACTThe ephrin type-A 2 receptor tyrosine kinase (EPHA2) is involved in the development and progression of various cancer types, including colorectal cancer (CRC). There is also evidence that EPHA2 plays a key role in the development of resistance to the endothelial growth factor receptor (EGFR) monoclonal antibody Cetuximab used clinically in CRC. Despite the promising pharmacological potential of EPHA2, only a handful of specific inhibitors are currently available. In this concept paper, general strategies for EPHA2 inhibition wit...
Source: ChemMedChem - September 22, 2023 Category: Chemistry Authors: Alix Tr öster Nathalie Jores Konstantin S Mineev Sridhar Sreeramulu Michael DiPrima Giovanna Tosato Harald Schwalbe Source Type: research
Targeting EPHA2 with Kinase Inhibitors in Colorectal Cancer
ChemMedChem. 2023 Sep 21:e202300420. doi: 10.1002/cmdc.202300420. Online ahead of print.ABSTRACTThe ephrin type-A 2 receptor tyrosine kinase (EPHA2) is involved in the development and progression of various cancer types, including colorectal cancer (CRC). There is also evidence that EPHA2 plays a key role in the development of resistance to the endothelial growth factor receptor (EGFR) monoclonal antibody Cetuximab used clinically in CRC. Despite the promising pharmacological potential of EPHA2, only a handful of specific inhibitors are currently available. In this concept paper, general strategies for EPHA2 inhibition wit...
Source: ChemMedChem - September 22, 2023 Category: Chemistry Authors: Alix Tr öster Nathalie Jores Konstantin S Mineev Sridhar Sreeramulu Michael DiPrima Giovanna Tosato Harald Schwalbe Source Type: research
Medicinal Chemistry-driven Approach to Novel 2-Substituted Benzoxazole - Estradiol Chimeras: Synthesis, Anticancer Activity and Early ADME Profile
ChemMedChem. 2023 Sep 20:e202300352. doi: 10.1002/cmdc.202300352. Online ahead of print.ABSTRACTThe efficient synthesis of novel estradiol-based A-ring-fused oxazole derivatives, which can be considered as benzoxazole-steroid domain-integrated hybrids containing a common benzene structural motif, is described. The target compounds were prepared from steroidal 2-aminophenol precursors by heterocycle formation or functional group interconversion (FGI) strategies. According to 2D projection-based t-distributed stochastic neighbor embedding (t-SNE), the novel molecules were proved to represent a new chemical space among steroi...
Source: ChemMedChem - September 20, 2023 Category: Chemistry Authors: Ferenc Kov ács Ildik ó Huliák H édi Árva M ónika Kiricsi D óra Erdős Marianna Kocsis Gergely Tak ács Gy örgy T Balogh Éva Frank Source Type: research
Water-Soluble Fullerene Monoderivatives for Biomedical Applications
ChemMedChem. 2023 Sep 20:e202300296. doi: 10.1002/cmdc.202300296. Online ahead of print.ABSTRACTMonoderivatives of fullerenes functionalized with hydrophilic groups make them water soluble, while preserving the hydrophobic fullerene cage. This class of molecules have intriguing biomedical applications, including drug delivery, photodynamic therapy (PDT), antiviral and antimicrobial activity and reactive oxygen species (ROS)-scavenging abilities. In this Concept we discuss the synthesis and biomedical applications of water-soluble fullerene monoderivatives and their biological behavior based on their structures.PMID:3772819...
Source: ChemMedChem - September 20, 2023 Category: Chemistry Authors: Rohin Biswas Cassiana Batista Da Rocha Ryan A Bennick Jianyuan Zhang Source Type: research
Medicinal Chemistry-driven Approach to Novel 2-Substituted Benzoxazole - Estradiol Chimeras: Synthesis, Anticancer Activity and Early ADME Profile
ChemMedChem. 2023 Sep 20:e202300352. doi: 10.1002/cmdc.202300352. Online ahead of print.ABSTRACTThe efficient synthesis of novel estradiol-based A-ring-fused oxazole derivatives, which can be considered as benzoxazole-steroid domain-integrated hybrids containing a common benzene structural motif, is described. The target compounds were prepared from steroidal 2-aminophenol precursors by heterocycle formation or functional group interconversion (FGI) strategies. According to 2D projection-based t-distributed stochastic neighbor embedding (t-SNE), the novel molecules were proved to represent a new chemical space among steroi...
Source: ChemMedChem - September 20, 2023 Category: Chemistry Authors: Ferenc Kov ács Ildik ó Huliák H édi Árva M ónika Kiricsi D óra Erdős Marianna Kocsis Gergely Tak ács Gy örgy T Balogh Éva Frank Source Type: research
Water-Soluble Fullerene Monoderivatives for Biomedical Applications
ChemMedChem. 2023 Sep 20:e202300296. doi: 10.1002/cmdc.202300296. Online ahead of print.ABSTRACTMonoderivatives of fullerenes functionalized with hydrophilic groups make them water soluble, while preserving the hydrophobic fullerene cage. This class of molecules have intriguing biomedical applications, including drug delivery, photodynamic therapy (PDT), antiviral and antimicrobial activity and reactive oxygen species (ROS)-scavenging abilities. In this Concept we discuss the synthesis and biomedical applications of water-soluble fullerene monoderivatives and their biological behavior based on their structures.PMID:3772819...
Source: ChemMedChem - September 20, 2023 Category: Chemistry Authors: Rohin Biswas Cassiana Batista Da Rocha Ryan A Bennick Jianyuan Zhang Source Type: research
Medicinal Chemistry-driven Approach to Novel 2-Substituted Benzoxazole - Estradiol Chimeras: Synthesis, Anticancer Activity and Early ADME Profile
ChemMedChem. 2023 Sep 20:e202300352. doi: 10.1002/cmdc.202300352. Online ahead of print.ABSTRACTThe efficient synthesis of novel estradiol-based A-ring-fused oxazole derivatives, which can be considered as benzoxazole-steroid domain-integrated hybrids containing a common benzene structural motif, is described. The target compounds were prepared from steroidal 2-aminophenol precursors by heterocycle formation or functional group interconversion (FGI) strategies. According to 2D projection-based t-distributed stochastic neighbor embedding (t-SNE), the novel molecules were proved to represent a new chemical space among steroi...
Source: ChemMedChem - September 20, 2023 Category: Chemistry Authors: Ferenc Kov ács Ildik ó Huliák H édi Árva M ónika Kiricsi D óra Erdős Marianna Kocsis Gergely Tak ács Gy örgy T Balogh Éva Frank Source Type: research
Water-Soluble Fullerene Monoderivatives for Biomedical Applications
ChemMedChem. 2023 Sep 20:e202300296. doi: 10.1002/cmdc.202300296. Online ahead of print.ABSTRACTMonoderivatives of fullerenes functionalized with hydrophilic groups make them water soluble, while preserving the hydrophobic fullerene cage. This class of molecules have intriguing biomedical applications, including drug delivery, photodynamic therapy (PDT), antiviral and antimicrobial activity and reactive oxygen species (ROS)-scavenging abilities. In this Concept we discuss the synthesis and biomedical applications of water-soluble fullerene monoderivatives and their biological behavior based on their structures.PMID:3772819...
Source: ChemMedChem - September 20, 2023 Category: Chemistry Authors: Rohin Biswas Cassiana Batista Da Rocha Ryan A Bennick Jianyuan Zhang Source Type: research
Exploring the translational gap of a novel class of Escherichia coli IspE inhibitors
ChemMedChem. 2023 Sep 17:e202300346. doi: 10.1002/cmdc.202300346. Online ahead of print.ABSTRACTDiscovery of novel antibiotics needs multidiscliplinary approaches to gain target enzyme and bacterial activity while aiming for selectivity over mammalian cells. Here we report a multi-parameter optimisation of a fragment-like hit that was identified through a structure-based virtual screening campaign on Escherichia coli IspE crystal structure. Subsequent medicinal chemistry design resulted in a novel class of E. coli IspE inhibitors, exhibiting activity also against the more pathogenic bacteria Pseudomonas aeruginosa and Acin...
Source: ChemMedChem - September 17, 2023 Category: Chemistry Authors: Henni-Karoliina Ropponen Eleonora Diamanti Sandra Johannsen Boris Illarionov Rawia Hamid Miriam Jaki Peter Sass Markus Fischer J örg Haupenthal Anna Katharina Herta Hirsch Source Type: research
Exploring the translational gap of a novel class of Escherichia coli IspE inhibitors
ChemMedChem. 2023 Sep 17:e202300346. doi: 10.1002/cmdc.202300346. Online ahead of print.ABSTRACTDiscovery of novel antibiotics needs multidiscliplinary approaches to gain target enzyme and bacterial activity while aiming for selectivity over mammalian cells. Here we report a multi-parameter optimisation of a fragment-like hit that was identified through a structure-based virtual screening campaign on Escherichia coli IspE crystal structure. Subsequent medicinal chemistry design resulted in a novel class of E. coli IspE inhibitors, exhibiting activity also against the more pathogenic bacteria Pseudomonas aeruginosa and Acin...
Source: ChemMedChem - September 17, 2023 Category: Chemistry Authors: Henni-Karoliina Ropponen Eleonora Diamanti Sandra Johannsen Boris Illarionov Rawia Hamid Miriam Jaki Peter Sass Markus Fischer J örg Haupenthal Anna Katharina Herta Hirsch Source Type: research
Click Chemistry and Targeted Degradation: A Winning Combination for Medicinal Chemists?
ChemMedChem. 2023 Sep 14:e202300422. doi: 10.1002/cmdc.202300422. Online ahead of print.ABSTRACTClick chemistry is universally recognized as a powerful strategy for the fast and precise assembly of diverse building blocks. Targeted Protein Degradation (TPD) is a new therapeutic modality based on heterobifunctional small-molecule degraders that provides new opportunities to medicinal chemists dealing with undruggable targets and incurable diseases. Here, we highlight how very recently the TPD field and that of click chemistry have merged, opening up the possibility for fine-tuning the properties of a degrader, chemically as...
Source: ChemMedChem - September 14, 2023 Category: Chemistry Authors: Anna Pasieka Eleonora Diamanti Elisa Uliassi Maria Laura Bolognesi Source Type: research
Novel 5-substituted uridines with activity against Gram-positive bacteria
ChemMedChem. 2023 Sep 14:e202300366. doi: 10.1002/cmdc.202300366. Online ahead of print.ABSTRACTThe emergence of drug-resistant strains of pathogenic microorganisms necessitates the creation of new drugs. A series of uridine derivatives containing an extended substituent at the C-5 position as well as C-5 alkyloxymethyl, alkylthiomethyl, alkyltriazolylmethyl, alkylsulfinylmethyl and alkylsulfonylmethyl uridines were obtained in order to explore their antimicrobial properties and solubility. It has been shown that new ribonucleoside derivatives have an order of magnitude better solubility in water compared to their 2'-deoxy...
Source: ChemMedChem - September 14, 2023 Category: Chemistry Authors: Dmitry A Makarov Sergey D Negrya Maxim V Jasko Inna L Karpenko Pavel N Solyev Vladimir O Chekhov Dmitry N Kaluzhny Olga V Efremenkova Byazilya F Vasilyeva Alexander O Chizhov Darya A Avdanina Alexander A Zhgun Sergey N Kochetkov Liudmila Alexandrova Source Type: research
Click Chemistry and Targeted Degradation: A Winning Combination for Medicinal Chemists?
ChemMedChem. 2023 Sep 14:e202300422. doi: 10.1002/cmdc.202300422. Online ahead of print.ABSTRACTClick chemistry is universally recognized as a powerful strategy for the fast and precise assembly of diverse building blocks. Targeted Protein Degradation (TPD) is a new therapeutic modality based on heterobifunctional small-molecule degraders that provides new opportunities to medicinal chemists dealing with undruggable targets and incurable diseases. Here, we highlight how very recently the TPD field and that of click chemistry have merged, opening up the possibility for fine-tuning the properties of a degrader, chemically as...
Source: ChemMedChem - September 14, 2023 Category: Chemistry Authors: Anna Pasieka Eleonora Diamanti Elisa Uliassi Maria Laura Bolognesi Source Type: research
Novel 5-substituted uridines with activity against Gram-positive bacteria
ChemMedChem. 2023 Sep 14:e202300366. doi: 10.1002/cmdc.202300366. Online ahead of print.ABSTRACTThe emergence of drug-resistant strains of pathogenic microorganisms necessitates the creation of new drugs. A series of uridine derivatives containing an extended substituent at the C-5 position as well as C-5 alkyloxymethyl, alkylthiomethyl, alkyltriazolylmethyl, alkylsulfinylmethyl and alkylsulfonylmethyl uridines were obtained in order to explore their antimicrobial properties and solubility. It has been shown that new ribonucleoside derivatives have an order of magnitude better solubility in water compared to their 2'-deoxy...
Source: ChemMedChem - September 14, 2023 Category: Chemistry Authors: Dmitry A Makarov Sergey D Negrya Maxim V Jasko Inna L Karpenko Pavel N Solyev Vladimir O Chekhov Dmitry N Kaluzhny Olga V Efremenkova Byazilya F Vasilyeva Alexander O Chizhov Darya A Avdanina Alexander A Zhgun Sergey N Kochetkov Liudmila Alexandrova Source Type: research
