ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Targeting the NF-κB and mTOR pathways with a quinoxaline urea analog that inhibits IKKβ for pancreas cancer therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- A Selective MAP3K1 Inhibitor Facilitates Discovery of NPM1 as a Member of the Network.Molecules (Basel, Switzerland) · 2025Article
- Diabetes mellitus drug discovery: insights into targeting feline and human amylin with small molecules.The veterinary quarterly · 2023Article
- IκB kinase β (IKKβ): Structure, transduction mechanism, biological function, and discovery of its inhibitors.International journal of biological sciences · 2023Review
- Small-molecule IKKβ activation modulator (IKAM) targets MAP3K1 and inhibits pancreatic tumor growth.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Stapling proteins in the RELA complex inhibits TNFα-induced nuclear translocation of RELA.RSC chemical biology · 2022Article
- Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy.European journal of medicinal chemistry · 2021Article
- Small molecule binding to inhibitor of nuclear factor kappa-B kinase subunit beta in an ATP non-competitive manner.Chemical communications (Cambridge, England) · 2021Article
- Isoforms of MUC16 activate oncogenic signaling through EGF receptors to enhance the progression of pancreatic cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Characterization of quinoxaline derivatives for protection against iatrogenically induced hearing loss.JCI insight · 2021Article
- CDK5 Inhibitor Downregulates Mcl-1 and Sensitizes Pancreatic Cancer Cell Lines to Navitoclax.Molecular pharmacology · 2019Article
- Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy.Bioorganic & medicinal chemistry letters · 2018Article
- Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage.Scientific reports · 2018Article
- Design, synthesis, and biological evaluation of novelDrug design, development and therapy · 2017Article
- Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.Journal of medicinal chemistry · 2016Article
- Improved therapy for neuroblastoma using a combination approach: superior efficacy with vismodegib and topotecan.Oncotarget · 2016Article
- Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-κB/LOX-1 Pathway.PloS one · 2016Article
- A quinoxaline urea analog uncouples inflammatory and pro-survival functions of IKKβ.Immunology letters · 2015Article
- Effect of NF-κB inhibition on chemoresistance in biliary-pancreatic cancer.Surgery today · 2015Review
- Inhibition of EP2/EP4 signaling abrogates IGF-1R-mediated cancer cell growth: involvement of protein kinase C-θ activation.Oncotarget · 2015Article
- Novel treatment for mantle cell lymphoma including therapy-resistant tumor by NF-κB and mTOR dual-targeting approach.Molecular cancer therapeutics · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe presence of TNF-α in approximately 50% of surgically resected tumors suggests that the canonical NF-κB and the mTOR pathways are activated. Inhibitor of IκB kinase β (IKKβ) acts as the signaling node that regulates transcription via the p-IκBα/NF-κB axis and regulates translation via the mTOR/p-S6K/p-eIF4EBP axis. A kinome screen identified a quinoxaline urea analog 13-197 as an IKKβ inhibitor. We hypothesized that targeting the NF-κB and mTOR pathways with 13-197 will be effective in malignancies driven by these pathways. EXPERIMENTAL
designRetrospective clinical and preclinical studies in pancreas cancers have implicated NF-κB. We examined the effects of 13-197 on the downstream targets of the NF-κB and mTOR pathways in pancreatic cancer cells, pharmacokinetics, toxicity and tumor growth, and metastases in vivo.
results13-197 inhibited the kinase activity of IKKβ in vitro and TNF-α-mediated NF-κB transcription in cells with low-μmol/L potency. 13-197 inhibited the phosphorylation of IκBα, S6K, and eIF4EBP, induced G1 arrest, and downregulated the expression of antiapoptotic proteins in pancreatic cancer cells. Prolonged administration of 13-197 did not induce granulocytosis and protected mice from lipopolysaccharide (LPS)-induced death. Results also show that 13-197 is orally available with extensive distribution to peripheral tissues and inhibited tumor growth and metastasis in an orthotopic pancreatic cancer model without any detectable toxicity.
conclusionThese results suggest that 13-197 targets IKKβ and thereby inhibits mTOR and NF-κB pathways. Oral availability along with in vivo efficacy without obvious toxicities makes this quinoxaline urea chemotype a viable cancer therapeutic.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.