Category: 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...

PTC-209 is a Specific BMI-1 Inhibitor and Impairs the Tumor Microenvironment

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor and refractory to existing therapies. BMI-1 is part of the polycomb repressive complex 1 (PRC1). There is a statistically significant correlation between the high frequency of BMI-1-positive tumor cells and poor prognosis of patients according to the data...

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...

SC99 is an Orally Active and Selective STAT3 Inhibitor

STAT3 is a member of the STAT protein family. STAT3 mediates the expression of a variety of genes in response to cell stimulation. So it plays a key role in many cell processes, such as cell growth and apoptosis. Specifically, the oncogenic STAT3 signaling pathway is becoming a promising...