Blog of Signaling Pathways

BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes

2 views | May 06 2021

Shuiyan Wu et al. thought that the BRD4 degrader ARV-825 could effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL. [Read the Full Post]

A fluorometric erythrophagocytosis assay using differentiated monocytic THP-1 cells to assess the clinical significance of antibodies to red blood cells

1 views | May 06 2021

Abdelwahab Hassan Ahmed Balola et al. thought that the flow cytometry-based erythrophagocytosis test described here was quantitative, highly reliable, and might be helpful for the assessment of the clinical significance of antibodies to RBCs. [Read the Full Post]

Selective Secretase Targeting for Alzheimer's Disease Therapy

1 views | May 05 2021

Alvaro Miranda et al. summarized structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities. [Read the Full Post]

Targeting MCL-1 dysregulates cell metabolism and leukemia-stroma interactions and resensitizes acute myeloid leukemia to BCL-2 inhibition

1 views | May 05 2021

Bing Z Carter et al. found that co-targeting MCL-1 and BCL-2 improved the efficacy of and overcame preexisting and acquired resistance to BCL-2 inhibition. [Read the Full Post]

Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor

1 views | May 04 2021

Zoltan Szlavik et al. reported the discovery of clinical candidate S64315, a selective small molecule inhibitor of Mcl-1. [Read the Full Post]

Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma

1 views | May 04 2021

Nabanita Mukherjee et al. suggested that several pro-apoptotic BCL2 family members, BCL2-like 11 (apoptosis facilitator) (BIM), phorbol-12-myristate-13-acetate-induced protein 1 (NOXA) or BID, played a role in the combination-induced effects. [Read the Full Post]

Direct Conjugation of NEDD8 to the N-Terminus of a Model Protein Can Induce Degradation

2 views | May 03 2021

Kartikeya Vijayasimha et al. suggested that under certain conditions, such as the model system described here, the covalent linkage of NEDD8 to a protein substrate might result in the target proteins degradation. [Read the Full Post]

IL33 (Interleukin 33)/ST2 (Interleukin 1 Receptor-Like 1) Axis Drives Protective Microglial Responses and Promotes White Matter Integrity After Stroke

1 views | May 03 2021

Di Xie et al. found that the IL33/ST2/STAT6 signaling as a potential immune regulatory mechanism to modulate microglia/macrophage activity, improved white matter integrity, and restored long-term neurological functions after stroke. [Read the Full Post]

Ibrutinib combinations in CLL therapy: scientific rationale and clinical results

1 views | May 01 2021

Natalia Timofeeva et al. found a new standard of care for CLL is expected to emerge from these investigations. [Read the Full Post]

SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243

1 views | May 01 2021

Yasuhisa Murai et al. found that findings uncover a previously unknown function of SLFN11 as a regulator of protein quality control and attenuator of ER stress and UPR. Moreover, they suggest the potential value of TAK-243 in SLFN11-deficient tumors. [Read the Full Post]

Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment

2 views | Apr 30 2021

Sophia Thy et al. thought that BETi could be used to "episensitize" UC cells to cytotoxic chemotherapy and inhibitors of DNA repair by inducing BRCAness in non BRCA1/2 mutated cancers. [Read the Full Post]

Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease

1 views | Apr 30 2021

Philipp von Hundelshausen et al. thought that specific platelet function tests in blood might help to estimate the probability of bleeding of newly developed BTKi. [Read the Full Post]

P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib

1 views | Apr 29 2021

Xiao-Ru Zhou et al. provided a promising combination therapy for MCL and highlighted the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor. [Read the Full Post]

AZ304, a novel dual BRAF inhibitor, exerts anti-tumour effects in colorectal cancer independently of BRAF genetic status

2 views | Apr 29 2021

Rui Ma et al. found that the BRAF inhibitor AZ304 had broad spectrum antitumour activity, which was significantly enhanced by combination with Cetuximab in colorectal cancers in vitro and in vivo. [Read the Full Post]

Combined blockade of polo-like kinase and pan-RAF is effective against NRAS-mutant non-small cell lung cancer cells

2 views | Apr 28 2021

Siyeon Park et al. found that human NRAS-mutant NSCLC cells were moderately sensitive to pan-RAF inhibitors. [Read the Full Post]

Mini review: The FDA-approved prescription drugs that target the MAPK signaling pathway in women with breast cancer

2 views | Apr 28 2021

Fatemeh Khojasteh Poor et al. summarized the FDA-approved prescription drugs that targeted the MAPK signaling pathway in women with BC. [Read the Full Post]

Glutamine deficiency promotes stemness and chemoresistance in tumor cells through DRP1-induced mitochondrial fragmentation

1 views | Apr 27 2021

Parash Prasad et al. suggested that glutamine deficiency in the core of tumors could increase the cancer stem cell population and the combination therapy with MDiVi-1 and L-DON was a useful approach to reduce CSCs population in tumor. [Read the Full Post]

MLL1 combined with GSK3 and MAP2K inhibition improves the development of in vitro-fertilized embryos

1 views | Apr 27 2021

Xuejie Han et al. found that the application of 3i provided a new method for improving IVF embryo production in domestic animals. [Read the Full Post]

CDK9 inhibition improves diabetic nephropathy by reducing inflammation in the kidneys

2 views | Apr 26 2021

Xiaojing Yang et al. suggested that CDK9 might serve as a potential therapeutic target for DN. [Read the Full Post]

Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs

3 views | Apr 26 2021

Zuzana Mrkvová et al. thought that a combination of TNF-α and smac mimetic could be a suitable strategy for overcoming resistance to therapy in cells unable to trigger apoptosis. [Read the Full Post]