| Description: |
NT157is a selective inhibitor of IRS-1/2, IC50 values at sub-micromolar doses (ranging from 0.3 to 0.8 μM) . |
| Target: |
IC50 value: 0.3 to 0.8 μM [1]
Target: Insulin receptor |
| In Vivo: |
NT157 suppresses growth of LNCaP xenografts following castration. NT157 treatment affects IGF1R and IRS targets in xenografts and significantly delays castration-resistant progression of LNCaP androgen-responsive xenografts when combined with castration. NT157 potentiates docetaxel activity in PC3 xenografts.[2] |
| In Vitro: |
NT157 significantly affects the cells' migratory ability, as confirmed by a wound-healing assay. NT157 induces cytostatic effects, as evidenced by G2/M cell cycle arrest, and does not affect apoptosis. NT157, a novel small-molecule that specifically targets IRS protein, in OS cells. NT157 is a small-molecule inhibitor that induces Ser-phosphorylation and consequently the degradation of IRS-1 and IRS-2. NT157 efficiently affects migration ability of MG-63 and U-2OS OS cells. NT157 treatment induces cell cycle arrest and inhibits IGF system signaling. [1] The density of LNCaP cells grown in FBS was decreased approximately 20% at 1 μM, approximately 70% at 2 μM, and >90% at 5 μM (IC50, 1.4 μM). Growth of LNCaP cells is suppressed >60% when cultured in CSS but still exhibited significant density at 2 μM and maximal decreased density at 5 μM. The density of FBS-cultured PC3 cells was similarly decreased by NT157 treatment (40% at 2 μM and > 70% at 5 μM; IC50, 2.5 μM). [2] |
| References: |
[1]. Garofalo C, et al. Preclinical Effectiveness of Selective Inhibitor of IRS-1/2 NT157 in Osteosarcoma Cell Lines. Front Endocrinol (Lausanne). 2015 May 13;6:74.
[2]. Ibuki N, et al. The tyrphostin NT157 suppresses insulin receptor substrates and augments therapeutic response of prostate cancer. Mol Cancer Ther. 2014 Dec;13(12):2827-39.
[3]. Ishii H, et al. miR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity. Nat Commun. 2018 Jul 4;9(1):2611. |
