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palbociclib + lenalidomide + dexamethasone

Development stage: Unknown
Lead developer: Pfizer
Modality: Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules
Administration: Oral

Overview

Palbociclib + lenalidomide + dexamethasone is a combination therapy being investigated for the treatment of relapsed or refractory multiple myeloma. The regimen consists of palbociclib (a CDK4/6 inhibitor), lenalidomide (an immunomodulatory drug), and dexamethasone (a corticosteroid). Palbociclib works by selectively inhibiting cyclin-dependent kinases 4 and 6, which prevents the phosphorylation of the retinoblastoma (Rb) protein and blocks cell cycle progression from the G1 to the S phase. Lenalidomide acts as a molecular glue that binds to the cereblon E3 ubiquitin ligase complex, leading to the degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), which are essential for myeloma cell survival. Dexamethasone provides synergistic anti-tumor activity by activating the glucocorticoid receptor to induce apoptosis. This triplet combination is being evaluated in Phase 1 clinical trials led by Weill Medical College of Cornell University to determine safety and efficacy in patients who have failed prior therapies.

Brand names: IbranceRevlimidDecadron
Other names: PD 0332991 + lenalidomide + dexamethasone

Targets

GR (Glucocorticoid receptor)CRBN (Cereblon)CDK6 (Cyclin-dependent kinase 6)CDK4 (Cyclin-dependent kinase 4)

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