Category: Myeloma

MS159 is a First-In-class NSD2 PROTAC degrader for Multiple Myeloma Research

Proteolytic targeting chimera (PROTAC) is a heterobifunctional small molecule, including two active domains, and a linker. Importantly, it can remove specific unwanted proteins. PROTAC is a technology based on the ligand binding of TAP and then the degradation of TAP. PROTAC provides an alternative approach to those so-called non-druggable...

Panobinostat is a Potent and Orally Active Non-selective HDAC Inhibitor

HDACs (Histone deacetylases) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because acetylation and de-acetylation can regulate DNA expression. Acetylation is controlled by two antagonistic enzyme families:...

Oprozomib (PR-047) is an Orally Active Peptide Epoxyketone Proteasome Inhibitor

Proteasome inhibition has been validated as a modality in the research of multiple myeloma and Non-Hodgkin’s lymphoma. The proteasome is a multicatalytic protease complex that is responsible for the ubiquitin-dependent turnover of cellular proteins. Proteasome substrates include misfolded or misassembled proteins as well as short-lived components of signaling cascades...

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....