pomalidomide

P1/2, N=246, Recruiting, BeOne Medicines | Active, not recruiting --> Recruiting

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.

P1/2, N=246, Active, not recruiting, BeOne Medicines | Recruiting --> Active, not recruiting

P2, N=28, Active, not recruiting, Medical College of Wisconsin | Recruiting --> Active, not recruiting | N=53 --> 28 | Trial completion date: Jan 2027 --> Jun 2027 | Trial primary completion date: Jan 2026 --> Apr 2027

These compounds incorporated the natural product CGA as the target-binding ligand, conjugated to pomalidomide (an E3 ligase-recruiting moiety) via various synthetic linkers. This study successfully applied an effective strategy for target identification and medication discovery of natural compounds. In addition, CGA-PROTAC A7 was synthesized in one step with an overall yield of 45.96%, providing a feasible route for synthesis and establishing a basis for the combination of natural product polyphenols with PROTAC technology.

Immunomodulatory imide drugs (IMiDs) like lenalidomide and pomalidomide are effective in treating multiple myeloma (MM) but pose hematotoxicity risks by degrading neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). Moreover, we have identified a CRBN ligand that mitigates these safety liabilities and can be effectively incorporated into PROTACs. This advancement provides a promising path toward safer preclinical development of PROTACs, especially as the field expands into chronic disease treatments beyond oncology.

Four LJH685-based PROTACs, composed of pomalidomide (a cereblon E3 ligase ligand) and different lengths of polyethylene glycol (PEG) linkers, decreased both total RSK2 and phosphorylated RSK2Ser227 levels in HMCLs...These results emphasize the critical role of linker length in optimizing PROTAC efficacy for targeting RSK2. Future exploration of diverse E3 ligases could enable optimization of PROTAC selectivity.

P3, N=500, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jan 2026 --> Jan 2029

P3, N=508, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting | Trial completion date: Apr 2029 --> Jul 2030

P1/2, N=162, Not yet recruiting, National Cancer Institute (NCI)

P=N/A, N=70, Recruiting, The Royal Wolverhampton Hospitals NHS Trust | Trial completion date: Feb 2026 --> Dec 2027 | Trial primary completion date: Feb 2026 --> Dec 2027

Herein, we report the synthesis of lenalidomide (63% overall yield) and pomalidomide (62% overall yield) using an integrated continuous flow platform with residence times of 42 minutes and 52 minutes, respectively. The products are obtained without the need for column chromatography, and both immunomodulatory imide drugs (IMiDs) can be accessed from a common intermediate through our developed route. Furthermore, we explore the synthesis of CRBN ligand-linkers under continuous flow, affording a series of derivatives with diverse properties in yields exceeding 90%.