News & Events
Lupeng Pharmaceutical presented the preclinical evaluation of the novel orally bioavailable MDM2-targeting PROTAC (NW-8-461) in acute leukemia and myelofibrosis, a small molecule innovative project, in form of poster at the AACR Annual Meeting 2026 (San Diego).
The poster described NW-8-461, a potent MDM2-targeting PROTAC that induces efficient MDM2 degradation with a DC₅₀ <1 nM and robust activation of p53 signaling in RS4;11 leukemia cells. NW-8-461 exhibits markedly enhanced antiproliferative activity, demonstrating approximately 10-fold and 100-fold greater potency in cell viability assays compared with RG7388 and AMG232, respectively. Consistent with a p53-dependent mechanism, NW-8-461 selectively inhibits cell viability in myelofibrosis cell lines harboring wild-type p53 but not mutant p53. Notably, at 1 µM, NW-8-461 shows minimal or no degradation of key off-target proteins, including IKZF1, IKZF3, SALL4, GSPT1, and CK1α, indicating high target selectivity. In mice, NW-8-461 demonstrates favorable pharmacokinetics and oral bioavailability, achieving a plasma C_max of 9,660 ng/mL following a single oral dose of 50 mg/kg. In an orthotopic RS4;11-Luc leukemia model, treatment with NW-8-461 at 25 mg/kg for 16 days resulted in complete eradication of leukemia cells in 7/7 mice and significantly superior efficacy compared with the MDM2 inhibitor RG7388. These results establish NW-8-461 as a differentiated and highly selective MDM2 degrader with strong therapeutic potential for p53-wild-type malignancies.
This poster was presented in Section 51 from 2:00 PM to 5:00 PM on April 19, 2026, with the number LB038/18, abstract link to
https://www.abstractsonline.com/pp8/#!/21436/presentation/11312
Declaration: The preclinical study data of the project released in this press release are preliminary, and the data may be updated and changed as the research progresses. This press release also contains forward-looking statements, which are based on current expectations and are subject to uncertainties and risks. Actual results may differ materially from those in the forward-looking statements. The company does not assume the obligation to update forward-looking statements.