pomalidomide

P1/2, N=153, Recruiting, GlaxoSmithKline | Phase classification: P1 --> P1/2 | N=55 --> 153

P2, N=52, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Jun 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P3, N=915, Recruiting, Regeneron Pharmaceuticals | Not yet recruiting --> Recruiting

P1, N=62, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2028 --> Jan 2029 | Trial primary completion date: Jan 2026 --> Jan 2028

P1, N=33, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Jun 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=50, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting | Trial completion date: Dec 2026 --> Dec 2030 | Trial primary completion date: Dec 2025 --> Dec 2028

P1, N=125, Recruiting, K36 Therapeutics, Inc. | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Dec 2025 --> Dec 2027

P3, N=944, Recruiting, Pfizer | Trial primary completion date: Dec 2025 --> Apr 2026

P3, N=810, Recruiting, Celgene | Trial primary completion date: Nov 2025 --> Jan 2027

The pomalidomide/thalidomide-based series (BP1-BP5) exhibited strong antiproliferative activity against leukemia and multiple myeloma cells, accompanied by degradation of CRBN neosubstrates. The hit compounds from both series, BP1 (DC50, 24 h = 20 nM, Dmax, 24 h = 99%) and BP6 (DC50, 24 h = 81 nM, Dmax, 24 h = 93%), demonstrated highly efficient and selective HDAC8 degradation. Pretreatment with BP6 enhanced the tumor suppressor p53 stability, thereby significantly increasing the sensitivity of leukemia cells to the MDM2 antagonist idasanutlin than PCI-34051, highlighting its unique potential for combinatorial therapy without impacting neosubstrates.

A bifunctional PROTAC, namely dSLC7A11, ws designed by conjugating the SLC7A11 inhibitor sulfasalazine to the CRBN ligand pomalidomide via an alkyl linker. Notably, dSLC7A11 exhibited superior antitumor efficacy over sulfasalazine alone, and achieved an effect of suppressing tumor growth by >65% in vivo. This study presented a SLC7A11-targeting PROTAC that disrupts the cellular antioxidant defense system, thus establishing a novel PROTAC-based approach for potent ferroptosis induction in cancer therapy.

Analysis of the FAERS database revealed that the PD-L1 inhibitor durvalumab is significantly associated with TB-related adverse events (reporting odds ratio = 7.81; 95% CI: 4.43-13.78; P = 1.10×10-18)...In silico drug prediction and molecular docking suggested several PD-L1-modulating compounds, including ruthenium, pomalidomide, zidovudine, and lycorine...Together, our findings define a mechanistic axis in CD14- CD16+ monocytes that underpins early TB control and is vulnerable to PD-L1 blockade. Collectively, these findings align with the established notion that assessing latent tuberculosis infection before initiating immune-modulating therapies is essential for minimizing reactivation risk, and propose tractable molecular targets for preventing TB reactivation in immunocompromised hosts.