Category: Myeloma

OTS514 is a Highly Potent TOPK Inhibitor with Anti-Myeloma Activity

Multiple myeloma represents a heterogeneous disease with various oncogenic mutations, chromosomal translocations, and copy number variations. The mitotic kinase T-LAK cell‐originated protein kinase/PDZ‐binding kinase ( TOPK/PBK) associates with the proliferation of tumor cells, maintenance of cancer stem cells, and poor patient prognosis in many cancers. In addition, TOPK plays...

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...

AZD4547 is a Potent FGFR Family Inhibitor

Fibroblast growth factors (FGF) and their receptors play important roles in multiple biologic processes, such as tissue repair, hematopoiesis, angiogenesis, and embryonic development. The FGFR family mainly comprises 4 main members (FGFR1–4). FGFRs and FGFRs FGF ligand binding can result in FGFR dimerization. In addition, receptor autophosphorylation and activation...

RRx-001 Triggers Apoptosis and Overcomes Drug Resistance in Myeloma

The hypoxic bone-marrow (BM) microenvironment confers growth/survival and drug-resistance in myeloma. Novel therapies via targeting hypoxic-BM milieu may overcome drug resistance. A study from Deepika Sharma Das reported a hypoxia-selective epigenetic agent, RRx-001. In this study, RRx-001 decreases the viability of MM cell lines, as well as overcomes drug-resistance....

AMG 232 is an Orally Active and Best-in-Class MDM2-p53 Inhibitor

The p53 tumor suppressor induces cell growth arrest and apoptosis in response to DNA damage or stress. And inactivation of the p53 pathway plays an indispensable role in tumor survival. Approximately p53 mutations resulting in loss of its function account for 50% human cancers. And the wild-type p53, present...

CP-10 is a Specific PROTAC Degrader of CDK6

CDK6 plays a significant role in cell cycle entrance. However, overexpression of CDK6 correlates to CDK4/6 inhibitor resistance in breast cancer cell lines and patient samples. Moreover, point mutation of CDK6 could possibly result in attenuation of drug binding affinity or hyperactivation of CDK6. Thus, there is an urgent...