thalidomide

P3, N=300, Active, not recruiting, Australasian Leukaemia and Lymphoma Group (ALLG) | Recruiting --> Active, not recruiting

Cereblon (CRBN) is the target of thalidomide derivatives1 that achieve therapeutic efficacy against some haematologic neoplasias2-4 by recruiting neosubstrates for degradation5-7...Structural investigations provide a mechanistic basis for the effects of the allosteric ligand by shifting the conformational distribution of CRBNopen to a novel CRBNint and increasing the CRBNclosed state. The discovery of a cryptic allosteric binding site on CRBN that alters the functional effects of orthosteric ligands opens new directions with broad implications for improving the selectivity and efficacy of CRBN therapeutics.

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...Methyl ester analogs of these compounds led to substantial proteasomal degradation of the TEAD•YAP/TAZ complex in cancer cells. This work provides a strategy for depletion of nuclear YAP and TAZ and for exploration of their TEAD-dependent and TEAD-independent activities in vivo .

P=N/A, N=545, Completed, Shanghai Zhongshan Hospital

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.

P2/3, N=222, Not yet recruiting, Shanghai Zhongshan Hospital

P2, N=45, Not yet recruiting, Medicines Development for Global Health | Initiation date: Oct 2025 --> Jan 2026

P2, N=112, Completed, University of Leeds | Unknown status --> Completed | Trial completion date: Jan 2021 --> Jan 2025

Initial therapy comprised high-dose methylprednisolone, intravenous immunoglobulin and thalidomide, followed by surgical resection and adjuvant thalidomide-cyclophosphamide-prednisone. Postoperatively, inflammatory indices normalized and mucocutaneous lesions partially improved; nevertheless, the patient died of respiratory failure 6 months after surgery. In summary, the present case report aimed to provide valuable references and experiences for clinicians in the diagnosis and treatment of CD featuring PNP and FDCS.

A 36-year-old woman with recurrent aphthous stomatitis had not responded to treatment with colchicine, pentoxifylline, azathioprine, dapsone or mycophenolate mofetil...A 49-year-old woman with severe recalcitrant cutaneous discoid lupus erythematosus (CDLE), systemic lupus and Raynaud phenomenon with chilblains had not responded to, had intolerance to or had adverse side-effects with multiple systemic agents including hydroxychloroquine, mepacrine, dapsone, rituximab biosimilar, mycophenolate mofetil, fumaric acid esters, acitretin, ciclosporin, thalidomide (tremor/loss of concentration), belimumab and methotrexate...Baseline and renal function monitoring is required for dose adjustment, and strict adherence to pregnancy prevention programmes is necessitated due to teratogenicity. Our three cases demonstrate lenalidomide to be a clinically beneficial, fast-acting and well-tolerated alternative off-label option for recalcitrant inflammatory dermatoses.

P2, N=26, Completed, AIDS Malignancy Consortium | Trial completion date: Jan 2026 --> Apr 2025 | Active, not recruiting --> Completed

During maintenance therapy with sorafenib combined with ITI, median relapse-free survival (mRFS) was also not reached, with 12- and 24-month RFS rates of 73.7% (14/19) and 57.9% (11/19), respectively. The sorafenib combined with ITI regimen is an effective maintenance therapy for FLT3-ITD (+) AML, significantly reducing relapse risk and prolonging survival.