Category: Multiple Myeloma

Iberdomide (CC-220) is an Orally Active Cereblon (CRBN) E3 Ligase Modulator (CELMoD)

Cereblon (CRBN) is a key protein in autosomal recessive nonsyndromic mental retardation. Specifically, it plays an intermediary role in helping immunomodulatory drugs play their immunomodulatory and tumor-killing roles. Besides, CRBN is highly conserved from plants to mammals, and mRNA expression in humans, rats, and mice is common. CRBN interacts...

M3258 is an Orally Active and Highly Selective LMP7 (β5i) Inhibitor

The ubiquitin-proteasome system (UPS) plays an essential role in maintaining cellular homeostasis by degrading ubiquitinated proteins. The immunoproteasome and constitutive proteasome are multisubunit cylindrical complexes each containing three proteolytic subunits; large multifunctional peptidase 2 (LMP2/β1i/PSMB9), MECL-1 (LMP10/β2i/PSMB10), and LMP7 (β5i/PSMB8) in the immunoproteasome, replaced, respectively, by β1 (β1c/PSMB6), β2...

Lenalidomide, a Ligand of CRBN, is an Orally Active Immunomodulator

Immunomodulatory imide drugs (IMiDs) are a class of immunomodulatory drugs containing an imide group. The discovery of anti-angiogenic and anti-inflammatory properties promoted the development of Thalidomide analogs. These compounds bind Cereblon (CRBN), the substrate adaptor for the CRBN-CRL4 E3 ubiquitin ligase, and modulate the substrate specificity of the enzyme....

dCBP-1 is a Selective PROTAC Degrader of p300/CBP

The paralogous chromatin regulators CREB-binding protein (CBP) and p300 are factors critical for establishing and activating enhancer-mediated transcription. The CREB-binding protein (CBP) and p300 are important factors for activating enhancer-mediated transcription. These proteins consist of at least 10 distinct functional domains. Most of them interact with over 400 other proteins,...

BMS-P5 is an Orally Active PAD4 Inhibitor

Multiple myeloma (MM), a kind of plasma cell malignancy, grows preferentially in the bone marrow (BM). Neutrophils serve as the first line of defense against a wide range of pathogens, by utilizing two major mechanisms: phagocytosis and degranulation. Recently, the formation of NETs represents another host defense mechanism of...

LBW242 is a Potent and Orally Active Proapoptotic IAP Inhibitor

Acute myelogenous leukemia (AML) is a hematologic malignancy. The characteristics include a block in cellular differentiation and aberrant growth of myeloid precursor cells. Approximately 30% of AML patients and a portion of acute lymphoblastic leukemia (ALL) patients express a mutated form of the class III receptor tyrosine kinase, FLT3....

E64FC26 is a pan-Inhibitor of the Protein Disulfide Isomerase (PDI) Family

Multiple myeloma (MM) is an incurable hematological malignancy. MM results in the accumulation of clonal plasma cells within the bone marrow. The natural biology of the plasma cell makes MM uniquely sensitive to disruptions in protein homeostasis. Subsequently, it proposes targeting protein folding as a strategy for the treatment...