P3, N=306, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Feb 2027

P2, N=180, Recruiting, Elevara Medicines Limited | Not yet recruiting --> Recruiting

P=N/A, N=50, Affiliated Hospital of North Sichuan Medical College; Affiliated Hospital of North Sichuan Medical College

Febuxostat is a selective XOD inhibitor, designed to target XOD, and thalidomide functions as a ligand for the Cereblon (CRBN) E3 ubiquitin ligase. Furthermore, the DeXOD can ameliorate glomerular capsular dilatation and renal tubular epithelial damage, while demonstrating no observable hepatotoxic effects. This strategy effectively circumvents the therapeutic limitations of conventional xanthine oxidase inhibitors, thereby offering a promising therapeutic paradigm for hyperuricemia and its complications.

We design and synthesize heterobifunctional molecules that consist of flufenamic acid analogs that bind to the allosteric TEAD lipid pocket, a long and flexible linker, and thalidomide to engage E3 ubiquitin ligase component cereblon. Proteasomal degradation of TEAD, YAP, and TAZ for the carboxylic acid compounds was modest, but methyl ester analogs led to substantial degradation of these proteins in cancer cells. This work provides a strategy for depletion of YAP and TAZ and for exploration of their TEAD-dependent and TEAD-independent activities in vivo.

P4, N=312, Recruiting, Sixth Affiliated Hospital, Sun Yat-sen University

Beyond protein degradation, the diverse biological activities of thalidomide are discussed, including modulation of cytokines, angiogenesis, and immune signaling pathways. Collectively, thalidomide exemplifies how mechanistic insight, synthetic innovation and careful risk-benefit evaluation can transform a once-discarded molecule into a cornerstone of contemporary drug design.

P4, N=108, Recruiting, Chinese University of Hong Kong

P2, N=201, Completed, Inmune Bio, Inc. | Active, not recruiting --> Completed

P3, N=138, Completed, Air Force Military Medical University, China | Recruiting --> Completed

We discuss clinical evidence, limitations, and practical considerations for sirolimus, PI3K inhibitors, thalidomide, MEK inhibitors, and KRAS-directed agents, as well as emerging combination and intermittent strategies to balance efficacy and toxicity...Targeted therapies are shifting management from procedure-centered to biology-guided care. Future progress depends on standardized molecular testing, patient-centered outcomes, and optimized treatment duration to achieve durable disease control with acceptable long-term toxicity.

P2, N=11, Terminated, Inmune Bio, Inc. | Active, not recruiting --> Terminated; Sponsor resource allocation