NT157

**NT157** is a synthetic small-molecule tyrphostin that selectively inhibits insulin receptor substrate proteins (IRS-1/2) by inducing their serine phosphorylation, leading to degradation and suppression of downstream signaling from IGF-1R, insulin receptor (InR), and other pathways. It demonstrates broad antineoplastic activity across multiple cancer types, including breast (particularly ERα+ and tamoxifen-resistant), lung, osteosarcoma, melanoma, prostate, colorectal, polycythemia vera, and acute lymphoblastic leukemia, by inhibiting cell proliferation, inducing cell cycle arrest (G2/M or S phase), promoting apoptosis, reducing migration and clonogenicity, and downregulating oncogenes like CCND1 while upregulating apoptotic genes like CDKN1A. Additional mechanisms include inhibition of STAT3/5 (via phosphatase activation), JAK2, NFκB, AXL, and activation of JNK and AP-1; it potentiates effects of EGFR inhibitors (e.g., gefitinib) and rapalogs (e.g., rapamycin). Initially developed as an IGF1R allosteric inhibitor, it targets IRS adaptor proteins more directly, showing preclinical efficacy in vitro and in vivo without reported clinical trials or developers.