Importantly, pharmacological administration of AZD-7762 significantly ameliorated disease severity in mouse models of NLRP3-driven diseases, including lipopolysaccharide (LPS)-induced systemic inflammation and dextran sulfate sodium (DSS)-induced colitis. Our findings reveal a novel function for AZD-7762 and suggest that it is a promising therapeutic candidate for the treatment of NLRP3-related inflammatory disorders.

In this issue of Cell Chemical Biology, Guo et al.1 reveal that the Checkpoint kinase 1 (CHK1) inhibitor Prexasertib moonlights as an AMP-activated protein kinase (AMPK) inhibitor that primes cancer cells for destruction. This off-target synergy highlights that serendipitous promiscuity can supercharge the efficacy of some "selective" kinase inhibitors.

P1, N=85, Terminated, Boundless Bio, Inc. | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Mar 2026; Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.

Combined CHK1/CHK2 inhibitor therapy shows a synergistic anti-tumor effect against neuroblastoma cells. Combination therapy impairs DNA damage response pathways and drives accelerated cell cycle progression in neuroblastoma cells. Combination therapy increases DNA damage, replication stress, and apoptosis marker expression. Combined CHK1/CHK2 inhibition holds therapeutic potential for the treatment of neuroblastoma.

Single-cell RNA sequencing analysis mapped the hub genes interleukin 22 receptor subunit alpha 1 (IL22RA1) and family with sequence similarity 221 member A (FAM221A) to epithelial cell populations and associated them with proliferative and DNA repair programs, supporting their role in tumor progression, supporting their role in ESCC progression. In vitro assays confirmed that IL22RA1 and FAM221A promote ESCC cell proliferation, migration, and invasion. Taken together, this AI-driven multi-omics framework delivers a prognostic model, defines biologically distinct ESCC subgroups, and nominates AZD7762 as a rational multitarget drug repurposing candidate, providing a precision oncology strategy.

Recently, we demonstrated that the response to Lenvatinib is associated with alterations in TP53 gene or protein. Moreover, Doxorubicin potentiated the Prexasertib effects in p53-defective thyroid cancer cells, yet at the lowest doses. This study unravels the potential of Prexasertib as a novel treatment option for aggressive thyroid cancers p53-defective and poorly responsive to tyrosine kinase inhibitors.

ADGRF4 and ADGRL4 were significantly overexpressed in STAD and independently associated with poor prognosis. Expression of these genes was correlated with changes in tumor microenvironment and immune cell infiltration, indicating their potential association in STAD progression. These findings suggest that ADGRF4 and ADGRL4 could serve as novel prognostic biomarkers with potential therapeutic significance in gastric cancer.

P2, N=401, Recruiting, Acrivon Therapeutics | Trial completion date: Apr 2027 --> Nov 2027 | Trial primary completion date: Oct 2026 --> May 2027

P2, N=353, Recruiting, Acrivon Therapeutics | N=72 --> 353

P1, N=570, Not yet recruiting, Sanofi

P2, N=72, Recruiting, Acrivon Therapeutics | N=48 --> 72

P1/2, N=48, Not yet recruiting, Acrivon Therapeutics Inc.