Pyrrolopyrazine Compounds as ERK5 Inhibitors for Treating Cancer DOI Creative Commons
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 16(1), С. 16 - 17

Опубликована: Дек. 11, 2024

InfoMetricsFiguresRef. ACS Medicinal Chemistry LettersASAPArticle This publication is free to access through this site. Learn More CiteCitationCitation and abstractCitation referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse Patent HighlightDecember 11, 2024Pyrrolopyrazine Compounds as ERK5 Inhibitors for Treating CancerClick copy article linkArticle link copied!Ram W. Sabnis*Ram SabnisSmith, Gambrell & Russell LLP, 1105 Peachtree Street NE, Suite 1000, Atlanta, Georgia30309, United States*E-mail: [email protected]More by Ram Sabnishttps://orcid.org/0000-0001-7289-0581Open PDFACS LettersCite this: Med. Chem. Lett. 2024, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00580https://doi.org/10.1021/acsmedchemlett.4c00580Published December 2024 Publication History Received 1 2024Published online 11 2024editorialPublished American Chemical Society. available under these Terms of Use. Request reuse permissionsAbstractClick section linkSection copied!High Resolution ImageDownload MS PowerPoint SlideProvided herein are novel pyrrolopyrazine compounds inhibitors, pharmaceutical compositions, use such in treating cancer, processes preparing compounds.This licensed personal The PublicationsPublished SocietySubjectswhat subjectsArticle subjects automatically applied from the Subject Taxonomy describe scientific concepts themes article.CancerCell physiologyInhibitorsPeptides proteinsPharmaceuticals Important Compound Classes TitlePyrrolopyrazine Compounds, Preparation Thereof Therapeutic Uses NumberWO 2024/218235 A1URL: https://patents.google.com/patent/WO2024218235A1/en DateOctober 24, Priority ApplicationEP 23315084.6 DateApril 19, 2023 InventorsSlowinski, F.; Zhang, J.; Dommergue, A. Assignee CompanySanofi, France Disease AreaCancer Biological TargetERK5 SummaryThe mitogen-activated protein kinase (MAPK) cascade a highly conserved cellular pathway which transmits signals cell surface nucleus. Proteins include extracellular signal-regulated (ERK) proteins; among those, (expressed MAPK7 gene) plays an important role proliferation well epithelial development differentiation.ERK5 controlling cycle progression. involvement numerous biological pathways means that its activity associated with many aspects cancer progression, including tumor angiogenesis, metastasis, inflammation, sustained proliferation, evasion growth suppression. inhibition thus represents promising approach tackle broad range cancers.The present application describes series inhibitors treatment cancer. Further, discloses compounds, their preparation, use, composition, treatment. DefinitionsR1 = -(C1–C6)alkyl, -(C3–C7)cycloalkyl, 4- 10-membered heterocycloalkyl, wherein R1 optionally substituted one or more RA;L1 direct bond, -O-, -NH-;R2 -(C3–C6)cycloalkyl, -(C6–C10)aryl, R2 three RB;R3 H, -(C1–C3)alkyl, OH;Y CH, N; n 0, 1. Key Structures AssayThe assay was performed. described were tested ability inhibit ERK5. IC50 values (nM) shown following table. DataThe table below shows representative data obtained testing examples. ClaimsTotal claims: 15Compound 14Pharmaceutical composition Recent Review ArticlesSee refs (1−6).Author InformationClick copied!Corresponding AuthorRam Sabnis, Smith, States, https://orcid.org/0000-0001-7289-0581, Email: protected]NotesThe author declares no competing financial interest.ReferencesClick copied! references 6 other publications. 1Shi, A.; Liu, L.; Li, S.; Qi, B. Natural products targeting MAPK-signaling cancer: overview. J. Cancer Res. Clin. Oncol. 150, 6, DOI: 10.1007/s00432-023-05572-7 Google ScholarThere corresponding record reference.2Islam, R.; Yen, K. P.; Izzati Mat Rani, N. N.; Hossain, M. S. advancement developing small molecular key against triple-negative breast Bioorg. 112, 117877, 10.1016/j.bmc.2024.117877 reference.3Ma, Y.; Wei, He, W.; Ren, Neutrophil traps MedComm 5, e647, 10.1002/mco2.647 reference.4Cersosimo, Lonardi, Ulivieri, C.; Martini, Morrione, Vermi, Giordano, Giurisato, E. CSF-1R Cancer: than Myeloid Cell Receptor. Cancers 16, 282, 10.3390/cancers16020282 reference.5Sabnis, R. Imidazopyridine Cancer. 15, 777– 778, 10.1021/acsmedchemlett.4c00228 reference.6Chen, Huang, H.; Fang, Hang, Q. ROS: A "booster" chronic inflammation metastasis. Biochim. Biophys. Acta, Rev. 1879, 189175, 10.1016/j.bbcan.2024.189175 reference.Cited By Click copied!This has not yet been cited publications.Download PDFFiguresReferences Get e-AlertsGet e-AlertsACS copied!https://doi.org/10.1021/acsmedchemlett.4c00580Published permissionsArticle Views219Altmetric-Citations-Learn about metrics closeArticle Views COUNTER-compliant sum full text downloads since November 2008 (both PDF HTML) across all institutions individuals. These regularly updated reflect usage leading up last few days.Citations number articles citing article, calculated Crossref daily. Find information counts.The Altmetric Attention Score quantitative measure attention research received online. Clicking on donut icon will load page at altmetric.com additional details score social media presence given article. how calculated.Recommended Articles FiguresReferencesAbstractHigh SlideReferences There reference.

Язык: Английский

Potential Therapeutic Targets in Triple‐Negative Breast Cancer Based on Gene Regulatory Network Analysis: A Comprehensive Systems Biology Approach DOI Creative Commons
Maryam Ahmadi, Neda Barkhoda, Azam Alizamir

и другие.

International Journal of Breast Cancer, Год журнала: 2024, Номер 2024(1)

Опубликована: Янв. 1, 2024

Background: Triple‐negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. This study aimed at identifying potential therapeutic targets in TNBC using gene regulatory network analysis and a system biology approach. Methods : The GSE38959 dataset was reanalyzed to identify differentially expressed genes (DEGs) tissues compared normal samples. Protein–protein interaction networks were constructed, hub identified. Survival performed GEPIA2. Gene built upstream regulators. Cross‐platform verification conducted independent RNA‐seq (GSE58135). Expression of prognostic markers versus non‐TNBC samples bc‐GenExMiner. Results: A total 943 DEGs identified tissues. CHEK1 PLK1 as central genes, overexpression correlating poor prognosis. GABPB1 the most influential regulator through analysis, while JUN exhibited interactions among 302 consistently modulated confirmed cross‐platform verification. validated by expression analysis. Conclusion provides insights into molecular mechanisms suggests CHEK1, PLK1, their regulators for treatment.

Язык: Английский

Процитировано

0
Boosting electrocatalytic alcohol oxidation: Efficient d–π interaction with modified TEMPO and bioinspired structure DOI
Ying Chen, Shibin Wang,

Zaixiang Xu

и другие.

AIChE Journal, Год журнала: 2024, Номер 71(3)

Опубликована: Ноя. 26, 2024

Abstract Aminoxyl radicals electrocatalysis presents a sustainable method for oxidizing alcohols into high‐value products. Nonetheless, the requirement high doses of aminoxyl diminishes product purity and economic viability. This study synthesized methylimidazole‐functionalized 4‐acetylamino‐2,2,6,6‐tetramethylpiperidine‐N‐oxyl derivative (MIAcNH‐TEMPO) with strongly electron‐withdrawing imidazole group combined it bioinspired nickel‐supported carbonaceous octopus tentacles effective electrooxidation alcohols, achieving current density 200 mA cm −2 , selectivity 99%, turnover frequency 26,490 h −1 . In situ experiments theoretical calculations indicated that synergistic effect Ni‐3d xz orbitals on tentacle surface interacting π MIAcNH‐TEMPO creates strong d–π interaction, which effectively facilitating creation locally intermediate‐enriched microenvironment, decreased required quantity radicals. Moreover, aqueous solubility reduces difficulty separation process. Scale‐up conducted in continuous flow electrolyzer showcased potential this strategy practical applications.

Язык: Английский

Процитировано

0
Pyrrolopyrazine Compounds as ERK5 Inhibitors for Treating Cancer DOI Creative Commons
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 16(1), С. 16 - 17

Опубликована: Дек. 11, 2024

InfoMetricsFiguresRef. ACS Medicinal Chemistry LettersASAPArticle This publication is free to access through this site. Learn More CiteCitationCitation and abstractCitation referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse Patent HighlightDecember 11, 2024Pyrrolopyrazine Compounds as ERK5 Inhibitors for Treating CancerClick copy article linkArticle link copied!Ram W. Sabnis*Ram SabnisSmith, Gambrell & Russell LLP, 1105 Peachtree Street NE, Suite 1000, Atlanta, Georgia30309, United States*E-mail: [email protected]More by Ram Sabnishttps://orcid.org/0000-0001-7289-0581Open PDFACS LettersCite this: Med. Chem. Lett. 2024, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00580https://doi.org/10.1021/acsmedchemlett.4c00580Published December 2024 Publication History Received 1 2024Published online 11 2024editorialPublished American Chemical Society. available under these Terms of Use. Request reuse permissionsAbstractClick section linkSection copied!High Resolution ImageDownload MS PowerPoint SlideProvided herein are novel pyrrolopyrazine compounds inhibitors, pharmaceutical compositions, use such in treating cancer, processes preparing compounds.This licensed personal The PublicationsPublished SocietySubjectswhat subjectsArticle subjects automatically applied from the Subject Taxonomy describe scientific concepts themes article.CancerCell physiologyInhibitorsPeptides proteinsPharmaceuticals Important Compound Classes TitlePyrrolopyrazine Compounds, Preparation Thereof Therapeutic Uses NumberWO 2024/218235 A1URL: https://patents.google.com/patent/WO2024218235A1/en DateOctober 24, Priority ApplicationEP 23315084.6 DateApril 19, 2023 InventorsSlowinski, F.; Zhang, J.; Dommergue, A. Assignee CompanySanofi, France Disease AreaCancer Biological TargetERK5 SummaryThe mitogen-activated protein kinase (MAPK) cascade a highly conserved cellular pathway which transmits signals cell surface nucleus. Proteins include extracellular signal-regulated (ERK) proteins; among those, (expressed MAPK7 gene) plays an important role proliferation well epithelial development differentiation.ERK5 controlling cycle progression. involvement numerous biological pathways means that its activity associated with many aspects cancer progression, including tumor angiogenesis, metastasis, inflammation, sustained proliferation, evasion growth suppression. inhibition thus represents promising approach tackle broad range cancers.The present application describes series inhibitors treatment cancer. Further, discloses compounds, their preparation, use, composition, treatment. DefinitionsR1 = -(C1–C6)alkyl, -(C3–C7)cycloalkyl, 4- 10-membered heterocycloalkyl, wherein R1 optionally substituted one or more RA;L1 direct bond, -O-, -NH-;R2 -(C3–C6)cycloalkyl, -(C6–C10)aryl, R2 three RB;R3 H, -(C1–C3)alkyl, OH;Y CH, N; n 0, 1. Key Structures AssayThe assay was performed. described were tested ability inhibit ERK5. IC50 values (nM) shown following table. DataThe table below shows representative data obtained testing examples. ClaimsTotal claims: 15Compound 14Pharmaceutical composition Recent Review ArticlesSee refs (1−6).Author InformationClick copied!Corresponding AuthorRam Sabnis, Smith, States, https://orcid.org/0000-0001-7289-0581, Email: protected]NotesThe author declares no competing financial interest.ReferencesClick copied! references 6 other publications. 1Shi, A.; Liu, L.; Li, S.; Qi, B. Natural products targeting MAPK-signaling cancer: overview. J. Cancer Res. Clin. Oncol. 150, 6, DOI: 10.1007/s00432-023-05572-7 Google ScholarThere corresponding record reference.2Islam, R.; Yen, K. P.; Izzati Mat Rani, N. N.; Hossain, M. S. advancement developing small molecular key against triple-negative breast Bioorg. 112, 117877, 10.1016/j.bmc.2024.117877 reference.3Ma, Y.; Wei, He, W.; Ren, Neutrophil traps MedComm 5, e647, 10.1002/mco2.647 reference.4Cersosimo, Lonardi, Ulivieri, C.; Martini, Morrione, Vermi, Giordano, Giurisato, E. CSF-1R Cancer: than Myeloid Cell Receptor. Cancers 16, 282, 10.3390/cancers16020282 reference.5Sabnis, R. Imidazopyridine Cancer. 15, 777– 778, 10.1021/acsmedchemlett.4c00228 reference.6Chen, Huang, H.; Fang, Hang, Q. ROS: A "booster" chronic inflammation metastasis. Biochim. Biophys. Acta, Rev. 1879, 189175, 10.1016/j.bbcan.2024.189175 reference.Cited By Click copied!This has not yet been cited publications.Download PDFFiguresReferences Get e-AlertsGet e-AlertsACS copied!https://doi.org/10.1021/acsmedchemlett.4c00580Published permissionsArticle Views219Altmetric-Citations-Learn about metrics closeArticle Views COUNTER-compliant sum full text downloads since November 2008 (both PDF HTML) across all institutions individuals. These regularly updated reflect usage leading up last few days.Citations number articles citing article, calculated Crossref daily. Find information counts.The Altmetric Attention Score quantitative measure attention research received online. Clicking on donut icon will load page at altmetric.com additional details score social media presence given article. how calculated.Recommended Articles FiguresReferencesAbstractHigh SlideReferences There reference.

Язык: Английский

Процитировано

0