^
4ms
Cancer-associated fibroblasts promote the progression and chemoresistance of HCC by inducing IGF-1. (PubMed, Cell Signal)
Inhibition of IGF-1R also enhanced the therapeutic effect of sorafenib on HCC, especially chemoresistant tumours. STATEMENT OF SIGNIFICANCE: Our study showed IL-6-IGF-1 axis played crucial roles in the crosstalk between HCC and CAFs, providing NT157 inhibited of STAT3 and IGF-1R as a new targeted therapy in combination with sorafenib.
Journal
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IL6 (Interleukin 6) • IGF1 (Insulin-like growth factor 1)
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IL6 expression
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sorafenib • NT-157
9ms
NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma. (PubMed, Hematol Transfus Cell Ther)
In summary, our study demonstrates that the IGF1/IGF1R/IRS signaling axis is differentially activated in MM cells and the NT157's capacity to modulate crucial molecular targets, promoting antiproliferative effects and apoptosis in MM cells. NT157 may offer a multifaceted approach to enhance MM therapy.
Journal
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IGF1R (Insulin-like growth factor 1 receptor) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IGF1 (Insulin-like growth factor 1) • IRS2 (Insulin receptor substrate 2) • RPS6 (Ribosomal Protein S6)
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STAT3 expression
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NT-157
1year
ERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation. (PubMed, NPJ Breast Cancer)
Of these, IRS1 stood out as a gene of interest, and ERα and PR occupancy at chromatin binding sites along IRS1 were uniquely altered in the context of ERα Y537S. Furthermore, siRNA knockdown of IRS1 or treatment with the IRS1 inhibitor NT-157 had a significant anti-proliferative effect in ERα Y537S cell lines, implicating IRS1 as a potential therapeutic target for restoring treatment sensitivity to patients with breast cancers harboring ERα Y537S mutations.
Journal
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ER (Estrogen receptor) • PGR (Progesterone receptor)
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ER Y537S • ESR1 mutation
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NT-157
over1year
LINC00638 promotes the progression of non-small cell lung cancer by regulating the miR-541-3p/IRS1/PI3K/Akt axis. (PubMed, Heliyon)
Repressing IRS1/2 using its inhibitor NT157 repressed LINC00638-mediated oncogenic effects. LINC00638 may function as an oncogene in NSCLC by modulating the miR-541-3p/IRS1/PI3K/Akt axis.
Journal
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IRS1 (Insulin Receptor Substrate 1)
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NT-157
over1year
Repressing IRS1/2 by NT157 inhibits the malignant behaviors of ovarian cancer through inactivating PI3K/AKT/mTOR pathway and inducing autophagy. (PubMed, Kaohsiung J Med Sci)
However, the autophagy inhibitor 3-MA partly reversed NT-157-mediated antitumor effects. In conclusion, this study disclosed that NT157 suppressed the malignant phenotypes of ovarian cancer cells by inducing autophagy and hampering the expression of IRS1/2 and PI3K/AKT/mTOR pathway.
Journal
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IRS1 (Insulin Receptor Substrate 1)
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NT-157
2years
NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells. (PubMed, Sci Rep)
NT157 also presented potentiating effects on EGFR inhibitors in lung cancer cells. In conclusion, our preclinical findings highlight NT157 as a putative prototype of a multitarget drug that may contribute to the antineoplastic arsenal against lung cancer.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • AXL (AXL Receptor Tyrosine Kinase) • CCND1 (Cyclin D1) • IRS2 (Insulin receptor substrate 2) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • IRS1 (Insulin Receptor Substrate 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • BBC3 (BCL2 Binding Component 3) • EGR1 (Early Growth Response 1)
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BCL2 expression • MYC expression • CCND1 expression
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NT-157
over2years
NT157 inhibits cell proliferation and sensitizes glioma cells to TRAIL-induced apoptosis by up-regulating DR5 expression. (PubMed, Biomed Pharmacother)
Importantly, combined administration of NT157 and TRAIL in vivo effectively inhibited glioma xenograft growth of nude mice by inhibiting cell proliferation and angiogenesis, and inducing DNA damage and apoptosis. Taken together, our findings validated the rational design that combined strategy of NT157 and TRAIL to trigger DNA damage and apoptosis by up-regulating DR5 could be a high efficient way to combat human glioma.
Journal • PARP Biomarker
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CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • TNFRSF10B (TNF Receptor Superfamily Member 10b)
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NT-157
over3years
NT157 Inhibits HCC Migration via Downregulating the STAT3/Jab1 Signaling Pathway. (PubMed, Technol Cancer Res Treat)
Finally, high mRNA expression levels of signal transducer and activator of transcription-3 and c-Jun activation domain-binding protein-1 in hepatocellular carcinoma were associated with significantly low survival rates. NT157 inhibits hepatocellular carcinoma migration and metastasis by downregulating the signal transducer and activator of transcription-3/c-Jun activation domain-binding protein-1 signaling pathway and targeting it may serve as a novel therapeutic strategy for the clinical management of hepatocellular carcinoma in the future.
Journal
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JUN (Jun proto-oncogene)
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NT-157
almost4years
NT157, an IGF1R-IRS1/2 inhibitor, exhibits antineoplastic effects in pre-clinical models of chronic myeloid leukemia. (PubMed, Invest New Drugs)
In human K562 cells and in murine Ba/F3 cells, engineered to express either wild-type BCR-ABL1 or the imatinib-resistant BCR-ABL1 mutant, NT157 inhibited BCR-ABL1, IGF1R, IRS1/2, PI3K/AKT/mTOR, and STAT3/5 signaling, increased CDKN1A, FOS and JUN tumor suppressor gene expression, and reduced MYC and BCL2 oncogenes. Exposure of primary CML cells harboring BCR-ABL1 to NT157 resulted in increased apoptosis, reduced cell proliferation and decreased phospho-CRKL levels. In conclusion, NT157 has antineoplastic effects on BCR-ABL1 leukemogenesis, independent of T315I mutational status.
Journal • IO biomarker
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BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CRKL (CRK Like Proto-Oncogene, Adaptor Protein) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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MYC expression • ABL1 T315I • BCR-ABL1 mutation
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imatinib • NT-157
4years
FGFR1 overexpression renders breast cancer cells resistant to metformin through activation of IRS1/ERK signaling. (PubMed, Biochim Biophys Acta Mol Cell Res)
Targeting IRS with IRS1 KO or IRS inhibitor NT157 significantly sensitized FGFR1 overexpressing cells to metformin. Moreover, we demonstrated that IRS1 functions as a critical mediator of the crosstalk between FGFR1 and IGF1R pathways, which involves a feedback loop between IRS1 and MAPK/ERK. Our study highlights the significance of FGFR1 status and IRS1 activation in metformin-resistance, which will facilitate the development of strategies targeting FGFR overexpression-associated metformin resistance.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • IGF1R (Insulin-like growth factor 1 receptor)
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FGFR1 overexpression • FGFR overexpression
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metformin • NT-157
over4years
NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2-positive myeloproliferative neoplasm cells. (PubMed, Signal Transduct Target Ther)
NT157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients (p < 0.05). These findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IRS1/2 proteins may represent a promising therapeutic strategy for MPN.
Journal
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ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • CCND1 (Cyclin D1) • IGF1R (Insulin-like growth factor 1 receptor) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IRS2 (Insulin receptor substrate 2) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
NT-157
almost5years
NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2-positive myeloproliferative neoplasm cells. (PubMed, Signal Transduct Target Ther)
NT157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients (p < 0.05). These findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IRS1/2 proteins may represent a promising therapeutic strategy for MPN.
Journal
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ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • CCND1 (Cyclin D1) • IGF1R (Insulin-like growth factor 1 receptor) • IRS2 (Insulin receptor substrate 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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NT-157