The Whole Proteome, Phosphoproteome, and Glycoproteome Landscape of Pan-Cancer Cell Lines Profiled by Mass Spectrometry and Reverse Phase Protein Array DOI Open Access
Wenhao Shi,

He Tianlong,

Nan Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Abstract Mammalian cancer cell lines are essential model systems in biomedical research. We conducted multi-level proteomics analyses on 54 widely used derived from various tissue-of-origins using two prominent technologies: mass spectrometry (MS) and reverse-phase protein array (RPPA). Our analysis identified 10,088 proteins, 33,609 phosphorylation sites across 7,289 phosphoproteins, 56,350 site-specific glycans 16,296 glycosylation 5,966 glycoproteins, along with 305 drug-relevant phosphoprotein targets. results reveal both consistent distinct patterns expression modification between MS RPPA, underscoring their complementary strengths as discovery tools. Additionally, we features that distinguish tissue origins different line lineages. This dataset supports system selection for drug target-related studies vitro provides valuable insights into key signaling pathways. Overall, this comprehensive resource enables new opportunities exploration biology offers significant value to research communities focused biomarker profiling, target discovery, understanding mechanisms diverse types.

Language: Английский

Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update DOI Creative Commons
Robert Roskoski

Pharmacological Research, Journal Year: 2024, Volume and Issue: 200, P. 107059 - 107059

Published: Jan. 11, 2024

Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one most important drug targets 21st century. There are 80 FDA-approved therapeutic agents that target about two dozen different kinases and seven these drugs were approved 2023. Of drugs, thirteen protein-serine/threonine kinases, four directed against dual specificity (MEK1/2), twenty block nonreceptor protein-tyrosine 43 inhibit receptor kinases. The data indicate 69 prescribed for treatment neoplasms. Six (abrocitinib, baricitinib, deucravacitinib, ritlecitinib, tofacitinib, upadacitinib) used inflammatory (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, ulcerative colitis). nearly multiple diseases. following received FDA approval 2023: capivasertib (HER2-positive breast cancer), fruquintinib (metastatic colorectal momelotinib (myelofibrosis), pirtobrutinib (mantle cell lymphoma, chronic lymphocytic leukemia, small lymphoma), quizartinib (Flt3-mutant acute myelogenous leukemia), repotrectinib (ROS1-positive lung ritlecitinib (alopecia areata). All orally effective with exception netarsudil, temsirolimus, trilaciclib. This review summarizes physicochemical properties all molecule inhibitors molecular weight, number hydrogen bond donors/acceptors, polar surface area, potency, solubility, lipophilic efficiency, ligand efficiency.

Language: Английский

Citations

167
Pyrimidine scaffold dual‐target kinase inhibitors for cancer diseases: A review on design strategies, synthetic approaches, and structure–activity relationship (2018‒2023) DOI
Minseok Song, Ahmed Elkamhawy,

Woojeong Noh

et al.

Archiv der Pharmazie, Journal Year: 2025, Volume and Issue: 358(1)

Published: Jan. 1, 2025

Abstract Cancer, the second leading cause of death globally, causes a significant threat to life. Despite advancements in treatment cancer, persistent challenges include severe side effects and emergence acquired drug resistance. Additionally, many traditional chemotherapy drugs show restricted efficacy high toxicity, primarily attributed their lack selectivity. Thus, development targeting protein kinases has emerged as noteworthy priority for addressing human cancers. Medicinal chemists have shown considerable interest dual candidates strategy create medicines that are safer, more efficient, cost‐effective. Furthermore, Food Drug Administration (FDA) approved several dual‐target anticancer treatment, emphasizing lower risks interactions improved pharmacokinetics safety profiles. This review focuses on synthetic efforts, design strategies, structure–activity relationship pyrimidine scaffold‐based kinase inhibitors developed with potential within recent 6 years (2018‒2023). Collectively, these strategies expected offer fresh perspectives future directions pyrimidine‐based design, potentially advancing cancer therapeutics.

Language: Английский

Citations

1
Molecular biology of the novel anticancer medications: a focus on kinases inhibitors, biologics and CAR T-cell therapy DOI
Eman M. Abdo,

Imad Ajib,

Jason El Mounzer

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Feb. 17, 2025

Language: Английский

Citations

1
Effects of the fatty acid synthase inhibitors triclosan and lapatinib on dengue virus and Zika virus infection DOI Creative Commons

Suthatta Sornprasert,

Janejira Jaratsittisin,

Chanida Chumchanchira

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 28, 2025

Fatty acid synthase (FASN) has been shown to be critical in the replication of several viruses genus Orthoflavivirus. In this study role two inhibitors FASN that work through different mechanisms were investigated dengue virus (DENV) and Zika (ZIKV) infections. Triclosan is a inhibitor targets enol reductase domain FASN, while lapatinib exerts an effect on acting HER2, upstream regulator FASN. After determining cytotoxicity, comprehensive analysis these drugs DENV 2 ZIKV infection was undertaken. The results showed triclosan had moderate antiviral activity against both (EC50 = 10.21 µM; Selective index (SI) 3.99) ( EC50 22.84 SI 5.49). Lapatinib reasonable 4.9 26.09), but computer modeling suggested potential directly by binding NS5. result better fit with NS5 than NS5, confirmed as for towards µM calculated 37.92. are consistent other studies use target domains suggesting simply targeting enzymatic insufficient therapeutic drug development, lapatinib, or similar molecules may have real potential.

Language: Английский

Citations

0
Properties of FDA-approved small molecule protein kinase inhibitors: a 2025 update DOI Creative Commons
Robert Roskoski

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107723 - 107723

Published: April 1, 2025

Because of the deregulation protein kinase action in many inflammatory diseases and cancer, family has become one most significant drug targets 21st century. There are 85 FDA-approved antagonists that target about two dozen different enzymes four these drugs were approved 2024 a fifth was 2025. Of drugs, five dual specificity kinases (MEK1/2), fourteen inhibit protein-serine/threonine kinases, twenty-one block nonreceptor protein-tyrosine 45 receptor kinases. The data indicate 75 prescribed for treatment neoplasms. Seven (abrocitinib, baricitinib, deucravacitinib, deuruxolitinib, ritlecitinib, tofacitinib, upadacitinib) management (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, ulcerative colitis). agents, used multiple diseases. following received FDA approval - deuruxolitinib (alopecia areata), ensartinib lazertinib (non-small cell lung cancer), tovorafenib (pediatric glioma) while mirdametinib 2025 type I neurofibromatosis (von Recklinghausen disease). Apart from netarsudil, temsirolimus, trilaciclib, blockers orally bioavailable. This article summarizes physicochemical properties all small molecule inhibitors including molecular weight, number hydrogen bond donors/acceptors, ligand efficiency, lipophilic polar surface area, solubility. A total 39 have least Lipinski rule 5 violation.

Language: Английский

Citations

0
Discovery of novel 4-trifluoromethyl-2-anilinoquinoline derivatives as potential anti-cancer agents targeting SGK1 DOI

Guangcan Xu,

Lanlan Li,

Mengfan Lv

et al.

Molecular Diversity, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 9, 2024

Language: Английский

Citations

1
Melt-blown polypropylene nonwoven as an efficient and eco-economic sorbent for pipette tip micro-solid phase extraction for the determination of tyrosine kinase inhibitors DOI
Jing Ye, Yuanyuan Zheng, Xiangyu Li

et al.

Analytica Chimica Acta, Journal Year: 2024, Volume and Issue: 1329, P. 343240 - 343240

Published: Sept. 12, 2024

Language: Английский

Citations

1
Potential protein kinase inhibitors that target G-quadruplex DNA structures in the human telomeric regions DOI
Bhavya Banjan, Abel John Koshy, Haritha Kalath

et al.

Molecular Diversity, Journal Year: 2024, Volume and Issue: 28(5), P. 3377 - 3391

Published: March 21, 2024

Language: Английский

Citations

0
The Whole Proteome, Phosphoproteome, and Glycoproteome Landscape of Pan-Cancer Cell Lines Profiled by Mass Spectrometry and Reverse Phase Protein Array DOI Open Access
Wenhao Shi,

He Tianlong,

Nan Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Abstract Mammalian cancer cell lines are essential model systems in biomedical research. We conducted multi-level proteomics analyses on 54 widely used derived from various tissue-of-origins using two prominent technologies: mass spectrometry (MS) and reverse-phase protein array (RPPA). Our analysis identified 10,088 proteins, 33,609 phosphorylation sites across 7,289 phosphoproteins, 56,350 site-specific glycans 16,296 glycosylation 5,966 glycoproteins, along with 305 drug-relevant phosphoprotein targets. results reveal both consistent distinct patterns expression modification between MS RPPA, underscoring their complementary strengths as discovery tools. Additionally, we features that distinguish tissue origins different line lineages. This dataset supports system selection for drug target-related studies vitro provides valuable insights into key signaling pathways. Overall, this comprehensive resource enables new opportunities exploration biology offers significant value to research communities focused biomarker profiling, target discovery, understanding mechanisms diverse types.

Language: Английский

Citations

0