Abstract 3392: Antitumor activity of a potent MNK inhibitor NSP-1047 in acute myeloid leukemia

Abstract

Abstract MAPK-interacting kinases (MNKs) phosphorylate the eukaryotic initiation factor 4E (eIF4E) and promote the synthesis of tumorigenic proteins. MAPK/MNK/eIF4E pathway is activated in many kinds of haematological and solid tumors. Here, we report the discovery of a novel polycyclic compound NSP-1047, which potently inhibits MNK1 and MNK2, and has sub-nanomolar cellular potency inhibiting phosphorylation of eIF4E. NSP-1047 potently inhibits the expression of multiple immune checkpoint proteins, including PD-1, Tim-3, and Lag-3, and it also inhibits the secretion of several inflammatory cytokines, such as IL-6, IL-8 and IL-10. NSP-1047 displays excellent ADME and pharmacokinetic properties, and demonstrates potent in vivo antitumor activity in acute myeloid leukemia animal models with tumor regression. Citation Format: Bing Li, Qionglin Huang, Ke Zhang, Jianming Zhang. Antitumor activity of a potent MNK inhibitor NSP-1047 in acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3392.