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DRUG CLASS:

ARF6 inhibitor

1year
ADP-Ribosylation Factor 6 Pathway Acts as a Key Executor of Mesenchymal Tumor Plasticity. (PubMed, Int J Mol Sci)
Thus, the ARF6-based pathway affects the TME and the intrinsic function of tumors, leading to malignancy. Here, we discuss the potential mechanisms of this ARF6-based pathway in tumorigenesis, and novel therapeutic strategies.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ASAP1 (ArfGAP With SH3 Domain)
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TP53 mutation • KRAS mutation • ASAP1 overexpression
almost2years
The small molecule inhibitor NAV-2729 has a complex target profile including multiple ADP-ribosylation factor regulatory proteins. (PubMed, J Biol Chem)
Finally, our screens identified 48 other possible targets of NAV-2729. These results illustrate the complexities of defining targets of small molecules and identify NAV-2729 as a model PH domain- binding inhibitor.
Journal
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ASAP1 (ArfGAP With SH3 Domain)
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NAV-2729
2years
Pharmacological Inhibition of Lipid Import and Transport Proteins in Ovarian Cancer. (PubMed, Cancers (Basel))
Overall, the small molecule inhibitors of lipid handling proteins BMS309403, HTS01037, NAV2729, SB-FI-26, and sulfosuccinimidyl oleate (SSO) caused a drug-specific, dose-/time-dependent inhibition of FA/LDL uptake, associated with reduced proliferation, cell cycle arrest, and apoptosis. Our findings indicate that OC cells are very sensitive to lipid deficiency. This dependency should be exploited for development of novel strategies against OC.
Journal
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CD36 (thrombospondin receptor) • CASP3 (Caspase 3) • ANXA5 (Annexin A5)
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NAV-2729
2years
Orchestration of mesenchymal plasticity and immune evasiveness via rewiring of the metabolic program in pancreatic ductal adenocarcinoma. (PubMed, Front Oncol)
In this review, we summarize our recent understanding of how PDAC cells acquire and augment mesenchymal features via metabolic and immunological changes during tumor progression, and how mesenchymal malignancies induce metabolic network rewiring and facilitate an immune evasive TME. In addition, we also present our recent findings on the interesting relevance of the small G protein ADP-ribosylation factor 6-based signaling pathway driven by KRAS/TP53 mutations, inflammatory amplification signals mediated by the proinflammatory cytokine interleukin 6 and RNA-binding protein ARID5A on PDAC metabolic reprogramming and immune evasion, and finally discuss potential therapeutic strategies for the quasi-mesenchymal subtype of PDAC.
Review • Journal
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IL6 (Interleukin 6) • ARID5A (AT-Rich Interaction Domain 5A)
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TP53 mutation • KRAS mutation
over2years
XIST sponges miR-320d to promote chordoma progression by regulating ARF6. (PubMed, J Bone Oncol)
Importantly, XIST silencing blocked xenograft tumor growth in vivo. XIST knockdown inhibited chordoma progression via regulating the miR-320d/ARF6 axis, providing a novel insight into chordoma pathogenesis.
Journal
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MIR320A (MicroRNA 320a) • XIST (X Inactive Specific Transcript)
over2years
Abrogation of ARF6 in promoting erastin-induced ferroptosis and mitigating capecitabine resistance in gastric cancer cells. (PubMed, J Gastrointest Oncol)
Additionally, our research demonstrated that ARF6 may control capecitabine resistance via several routes. ARF6 may play a critical role in the development of GC.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation
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capecitabine • erastin
over2years
CCL18 promotes breast cancer progression by exosomal miR-760 activation of ARF6/Src/PI3K/Akt pathway. (PubMed, Mol Ther Oncolytics)
Moreover, recipient MCF-7 cells could effectively uptake these miR-760-rich exosomes that significantly promoted proliferation, tumor growth in vivo, migration, invasion, and chemoresistance by activating ARF6-mediated Src/PI3K/Akt signaling and the epithelial-mesenchymal transition (EMT) pathway. Together, our results support that exosomal miR-760 secreted by CCL18-stimulated high metastatic BC cells promoted the malignant behaviors in low metastatic BC cells by up-regulating the ARF6-mediated Src/PI3K/Akt signaling pathway.
Journal
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ASAP1 (ArfGAP With SH3 Domain) • MIR760 (MicroRNA 760)
3years
Tris(dibenzylideneacetone)dipalladium(0) (Tris DBA) Abrogates Tumor Progression in Hepatocellular Carcinoma and Multiple Myeloma Preclinical Models by Regulating the STAT3 Signaling Pathway. (PubMed, Cancers (Basel))
Tris DBA significantly inhibited tumor growth in xenograft MM and orthotopic HCC preclinical mice models with a reduction in the expression of various prosurvival biomarkers in MM tumor tissues without displaying significant toxicity. Overall, Tris DBA functions as a good inhibitor of STAT3 signaling in preclinical HCC and MM models.
Preclinical • Journal
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JAK2 (Janus kinase 2) • IL6 (Interleukin 6) • JAK1 (Janus Kinase 1)
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STAT3 expression
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tris DBA palladium (Tris DBA)
3years
miR-28-3p inhibits prostate cancer cell proliferation, migration and invasion, and promotes apoptosis by targeting ARF6. (PubMed, Exp Ther Med)
Finally, rescue experiments demonstrated that ARF6 overexpression attenuated the effects of the miR-28-3p mimic by upregulating Rac1 and p-Erk1/2 expression in PCa cells. In conclusion, these findings indicated that miR-28-3p may inhibit the biological behaviors of PCa cells by targeting ARF6, and therefore may represent a novel therapeutic candidate for PCa.
Journal
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RAC1 (Rac Family Small GTPase 1)
over3years
[VIRTUAL] Association of high gene expression levels of ARF6 with the immune microenvironment and prediction of poor outcomes. (ASCO 2021)
This is the first report showing that high gene expression of ARF6 in PDAC indicates a different immune profile, is enriched in cancer metastases, and is associated with poor survival . Our results provide the first clinical evidence supporting the ARF6 pathway as a major downstream target of KRAS and TP53 mutations promoting immune evasion, suggesting ARF6 is a novel marker for prognosis and a potential target for immune therapeutic strategies in PDAC.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • KDM6A (Lysine Demethylase 6A) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD4 (CD4 Molecule) • ASAP1 (ArfGAP With SH3 Domain) • FANCD2 (FA Complementation Group D2) • TFEB (Transcription Factor EB 2)
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PD-L1 expression • TP53 mutation • KRAS mutation • STK11 mutation • TP53 mutation + KRAS mutation • IDO1 expression • IFNG expression • KRAS mutation + TP53 mutation
almost4years
Sevoflurane Suppresses the Migration, Invasion, and Epithelial-Mesenchymal Transition of Breast Cancer Cells Through the miR-139-5p/ARF6 Axis. (PubMed, J Surg Res)
SEV suppressed the migration, invasion, and EMT of BC cells through downregulating the abundance of ARF6 by upregulating miR-139-5p. The miR-139-5p/ARF6 axis might be a promising target for the treatment of BC.
Preclinical • Journal
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CDH1 (Cadherin 1) • FN1 (Fibronectin 1) • MIR139 (MicroRNA 139)
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miR-139-5p expression
4years
Tris DBA ameliorates IgA nephropathy by blunting the activating signal of NLRP3 inflammasome through SIRT1- and SIRT3-mediated autophagy induction. (PubMed, J Cell Mol Med)
In conclusion, Tris DBA effectively ameliorated the mouse IgAN model and targeted signalling pathways downstream of ICs-mediated interaction, which is a novel immunomodulatory strategy. Further development of Tris DBA as a therapeutic candidate for IgAN is warranted.
Journal
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SIRT1 (Sirtuin 1)
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tris DBA palladium (Tris DBA)
over4years
Palladium based nanoparticles for the treatment of advanced melanoma. (PubMed, Sci Rep)
Surprisingly, the HANP containing IGF1R antibody was less effective than particles without antibody, possibly due to steric hindrance of IGF1R and CD44 binding. Tris DBA-Pd nanoparticles are an effective therapy for CD44-positive tumors like melanoma, and further development of these nanoparticles should be pursued.
Journal
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BRAF (B-raf proto-oncogene) • IGF1R (Insulin-like growth factor 1 receptor) • CD44 (CD44 Molecule)
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BRAF mutation
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tris DBA palladium (Tris DBA)