Design, development of pyrazole‐linked spirocyclopropyl oxindole‐carboxamides as potential cytotoxic agents and Type III allosteric VEGFR‐2 inhibitors DOI Open Access

Durgesh Gurukkala Valapil,

Geetanjali Devabattula, Akash P. Sakla

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(22)

Published: Aug. 1, 2024

Abstract Tumor progression depends on angiogenesis, which is stimulated by growth factors like VEGF, targeting VEGFR kinase with small molecules an effective anti‐angiogenic therapeutic approach. The rational modification of sunitinib (VEGFR‐2 inhibitor) to spirocyclopropyloxindoline carboxamides have been performed and their in vitro cytotoxic profiling was evaluated. molecular modelling studies enabled the screening designed analogues identifying possible interactions within type III allosteric inhibitor binding site VEGFR‐2. biological synthesized compounds 15 a – y , revealed ability compound w inhibit cell MCF‐7 line IC 50 value 3.87±0.19 μM alongside inhibition VEGFR‐2 at concentration 4.34±0.13 observed. Also, validated through HUVEC tube formation assay. qualitative assessment apoptosis induction cells evaluated staining such as AO/EB DAPI staining, whereas quantification cycle analysis were FACS analysis. metastatic cancer migration scratch wound healing current study strives sequentially optimize structural attributes 3‐alkenyl oxindole core surpass existing challenges well‐known inhibitors. findings observed from this highlights that be prominent lead towards development clinical drug candidates.

Language: Английский

Molecular mechanisms and signaling pathways related to brain metastasis in breast cancer DOI Creative Commons

Zixin Liang,

Yanan Mo, Yujiao Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Brain metastasis in breast cancer (BCBM) significantly threatens the survival and quality of life patients, particularly those with triple-negative (TNBC) HER2-positive subtypes. It involves complex molecular mechanisms diverse signaling pathways. This review highlights recent research on pathways BCBM. The process BCBM includes several key steps: local infiltration cells into bloodstream subsequent spread to brain. They must then overcome blood-brain barrier (BBB) establish grow Multiple pathways, including PI3K/AKT, STAT3, NF-κB, Notch, Wnt are involved this process. Overall, is a disease regulated by multiple To improve patient life, it crucial deepen explore new treatment targets strategies. will enhance our understanding lead more effective treatments.

Language: Английский

Citations

0
Diabetic retinopathy: a comprehensive review of pathophysiology and emerging treatments DOI

Mukul Shyam,

Sidharth Sen,

Aleen Veronica

et al.

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: April 9, 2025

Language: Английский

Citations

0
Increase in Vascular Endothelial Growth Factor (VEGF) Expression and the Pathogenesis of iMCD-TAFRO DOI Creative Commons
Gordan Srkalović,

Sally Nijim,

Maya Blanka Srkalovic

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1328 - 1328

Published: June 14, 2024

TAFRO (thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (F/R), renal failure (R), and organomegaly (O)) is a heterogeneous clinical subtype of idiopathic multicentric Castleman disease (iMCD) associated with significantly poorer prognosis than other subtypes iMCD. symptomatology can also be seen in pathological contexts outside iMCD, but it unclear if those cases should considered representative different entity or simply severe presentation infectious, malignant, rheumatological diseases. While interleukin-6 (IL-6) an established driver iMCD-TAFRO pathogenesis subset patients, the etiology unknown. Recent case reports literature reviews on patients suggest that vascular endothelial growth factor (VEGF), interplay VEGF IL-6 concert, rather as single cytokine, may drivers for pathophysiology, especially injury. In this review, we discuss possible role pathophysiology manifestations iMCD-TAFRO. particular, involved pathology through its ability to activate RAS/RAF/MEK/ERK PI3K/AKT/mTOR signaling pathways. Further elucidating VEGF-IL-6 axis additional shed light therapeutic options treatment who do not respond to, otherwise relapse following, targeting drugs. This review investigates potential related pathways future.

Language: Английский

Citations

4
New indolin-2-ones, possessing sunitinib scaffold as HDAC inhibitors and anti-cancer agents with potential VEGFR inhibition activity; design, synthesis and biological evaluation DOI
Mozhdeh Yousefian, Maryam Hashemi, Vahid Eskandarpour

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108231 - 108231

Published: Jan. 30, 2025

Language: Английский

Citations

0
Low Phosphatidylserine+ Cells Within the CD34+/CD45dim/CD117(c-kit)+ Subpopulation are Associated with Poor Outcomes in Metastatic Colorectal Cancer DOI Open Access
Davide Brocco, Pasquale Simeone, Pietro Di Marino

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 499 - 499

Published: Feb. 2, 2025

Background: Colorectal cancer is among the most prevalent causes of tumor-related deaths worldwide. Antiangiogenic therapy represents a cornerstone metastatic CRC treatment, and biomarkers are advocated for optimization this therapeutic strategy. Methods: In observational prospective study, we employed an optimized flow cytometry protocol to investigate prognostic predictive potential blood circulating endothelial cells (CECs), progenitor (CEPCs), related subsets in cohort patients with colorectal (n = 40). Results: Computational FC analysis revealed differential enrichment cell clusters CD34+/CD45dim/CD117(c-kit)+ phenotype between responders non-responders both antiangiogenic non-antiangiogenic treatments. Intriguingly, our results show that high percentage annexin V-negative putative population CD34+/CD45dim/CD117+ was correlated reduced response systemic anticancer treatments (p 0.015) worse overall survival (log-rank p 0.03). addition, observed increased concentrations CD34+/CD45dim/CD117+/annexin V- higher number sites Conclusions: Overall, these findings hold promise identification novel develop more personalized treatment approaches cancer.

Language: Английский

Citations

0
Glyoxalase I Inhibitors Targeting Breast Cancer-Associated Endothelial Cells: An Integrated Network Pharmacology and Experimental Investigation DOI
Honglin Jiang, Lu Yang,

Qiuyue Sun

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141868 - 141868

Published: Feb. 1, 2025

Language: Английский

Citations

0
Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy DOI
Jing Jiao, You Wu, Shaoxian Wu

et al.

Current Treatment Options in Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Language: Английский

Citations

0
Unravelling key signaling pathways for the therapeutic targeting of non-small cell lung cancer DOI

P. Chavan,

Ruchi Pandey,

BHEEMANAGOUDA O. PATIL

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177494 - 177494

Published: March 1, 2025

Language: Английский

Citations

0
Pharmacovigilance in intraocular antiangiogenic therapy DOI

Marianne L. Shahsuvaryan

Cutaneous and Ocular Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8

Published: March 14, 2025

Anti-VEGF (Vascular endothelial growth factor) agents have revolutionized ophthalmotherapy and are vital for various retinal disease treatment in ophthalmic practice. Ophthalmology has witnessed an explosion the number of intravitreal injections delivered to patients over past years. The rising popularity anti-VEGF drugs came along with concerns about its safety clinical use. aim this focused review is critically analyze currently available findings on systemic safety. A literature search was conducted using PubMed, Web Science, Google Scholar databases studies published from January 2012 February 2025. reference lists meta-analyses selected were also reviewed. Eighty four articles high or medium relevance review. exclusion criteria included non-English language publications, directly unrelated topic, commentaries, conference abstracts. Systemic concern intraocular pharmacotherapy by antiangiogenic a strong body evidence, resulting plenty peer reviewed articles. It certainly becoming recognized that agents, despite given intraocularly, potential cause adverse events, such as cardiovascular, renal, neurological. Accumulating evidence obviate need raise medical professionals' awareness risk profile eye diseases treated anti-VEGF, paying special attention diabetes older multimorbidity. Early identification prompt management undesirable side effects secondary angiogenics can lessen severity, help achieve earlier resolution.

Language: Английский

Citations

0
Discovery of Novel Multiangiogenic Agents Targeting VEGFR2, EphB4, FGFR-1, and TIE-2: Receptor-Based Pharmacophore Modeling, Virtual Screening, and Molecular Modeling Studies DOI Creative Commons
Jeevan Patra, Amit K. Keshari, Richie R. Bhandare

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

The angiogenesis phenomenon is crucial for the formation of new blood vessels in cancer cells. cancerous cells' progress hampers other healthy main objective this study to explore and decipher multimodal natural compounds against VEGFR2, EphB4, FGFR-1, TIE-2 drug targets arrest progression. receptor-based pharmacophore modeling was developed validated through enrichment parameters. Further, hypothesis allowed screening druglike product databases such as SuperNatural 3.0, COCONUT, LOTUS. common pharmacophoric featured were assessed binding affinities using absolute end-point methods. Finally, density functional theory has been studied understand chemical reactivity stability protein complexes. Among all screened compounds, 17 found align accurately models having higher fitness scores scores. Taking reference drugs sorafenib (VEGFR2), NVP-BHG712 (EphB4), pemiganitib (FGFR-1), DP1919 (TIE-2), three promising CNP0003920, CNP0243075, CNP0211397 concluded based on their energies, interactions, molecular dynamics, optimal pharmacokinetic toxicity profiles. (DFT) results suggested that identified bound with complexes are stable. Our findings can represent a starting point developing analogues proteins.

Language: Английский

Citations

0