Signaling Pathway Product Solutions

Cancer cells are known to over-express a number of anti-apoptotic proteins that belong to the BCL2 family on the surface of the mitochondria. These proteins interact with pro-apoptotic proteins and regulate the intrinsic apoptotic pathway by controlling the mitochondrial membrane permeability and release of the pro-apoptotic factor cytochrome c that initiates activation of the caspase cascade and apoptosis. Eurofins DiscoverX offers novel, direct, cell-based assays to study these apoptotic players. These apoptosis signaling pathway assays are based on the InCELL Hunter^™ target engagement destabilization assay. The portfolio covers pre-validated cell lines and assay-ready kits that allow you to screen for protein interaction inhibitors (small molecules or siRNA) in an HTS-friendly and simple assay format.

cAMP-regulated transcriptional co-activators TORC1 (CRTC1) and TORC2 (CRTC2) are known to regulate the cAMP-responsive element-binding (CREB) protein. Rising intracellular cAMP levels lead to de-phosphorylation of CRTC1 and CRTC2 that leads to the translocation of CRTC to the nucleus. CRTC translocation is known to be regulated by AMPK (5′-AMP activated kinase), PKA, and SIK. TORC2 and AMPK are potential therapeutic targets for Type II Diabetes. Eurofins DiscoverX offers novel direct, functional cellular assays in the form of PathHunter cell lines and assay-ready kits for TORC1 (CRTC1) and TORC2 (CRTC2) translocation. These products enable measurement of compound effects on CRTC1 and CRTC2 translocation or for screening and profiling small molecules, siRNA, or inhibitors of upstream targets AMPK, S1K, or CRTC.

DNA damage results in cell cycle arrest, apoptosis, and the stabilization and repair of the cellular genome. The DNA damage PathHunter assay includes downstream targets such as ATM, ATR, CDC25A, Chk1, Chk2, Caspase 3, and p21, and signals through p53-dependent and -independent processes. Eurofins DiscoverX offers a novel direct, functional cellular assay for predictive toxicology that is reliable, easy to run, user-friendly, and compatible with 384 well protocols. This assay in the form of a cell line allows you to obtain the effect of your early stage compound on key cellular pathways such as DNA damage (p53) or ER stress. The cell line provides a scope for screening targets upstream of the p53 pathway or for studying compound toxicity profiles (genotoxic markers).

Nuclear factor kappa B (NF-κB) belongs to a family of transcription factors that play pivotal roles in inflammatory responses and immunological reactions. The NF-κB pathway can be activated by a variety of stimuli, including TNF-α (tumor necrosis factor alpha), interleukin 1 (IL-1), T and B cell mitogens, bacterial lipopolysaccharide (LPS), and viral proteins. Eurofins DiscoverX offers simple one-step degradation, reporter, and nuclear translocation assays to study the NF-κB pathway. These fully optimized, target-validated cell lines provide you convenience, relevant hits, and guaranteed performance for screening, profiling, or research applications, including monitoring the degradation of IκB or screening inhibitors for TNFα signaling or IκB kinases.

NRF2 [Nuclear factor (erythroid-derived 2)-like 2] and its downstream target genes are the primary cellular defense against the cytotoxic effects of oxidative stress. Cell damage due to free radicals from oxidative stress contributes to diseases such as arteriosclerosis, stroke, asthma, cardiac infarctions, Alzheimer’s disease, Parkinson’s disease, and cancer, making the NRF2 pathway a high-profile therapeutic target.

PI3K/AKT signaling regulates cellular processes such as proliferation, growth, survival, apoptosis, and the up regulation of hypoxia-related proteins. Screen for inhibitors to PI3 kinase and AKT and analyze receptor activation, phosphorylation, or downstream FOXO translocation in an HTS-friendly, cell-based format without the need for antibodies. Additionally, measure compound-target engagement though compound-induced stabilization of PI3Kδ target protein.

Membrane-bound transcription factors, sterol regulatory element binding protein-1 and -2 (SREBP-1 and SREBP-2), mediate cholesterol and fatty acids homeostasis. SREBP-2 monitors cellular cholesterol levels and responds to low levels of cholesterol by the transcription of genes for HMG-CoA Reductase and other enzymes involved in the cholesterol synthesis pathway. Recent studies implicate SREBP-2 in hypercholesterolemia, coronary heart disease, obesity, autophagy, and Alzheimer’s disease. Eurofins DiscoverX offers novel direct, functional cell-based assays for SREBP2 translocation capable of screening or profiling the SREBP cholesterol sensing pathway inhibitors and measuring the effect of compounds on SREBP2 translocation.

TGFβ (Transforming Growth Factor beta) is a small secreted polypeptide that signals through the type II serine/threonine kinase dimeric receptor (TGFβR2) that recruits and phosphorylates the type I dimeric receptor (TGFβR1). TGFβR1 phosphorylates and activates the SMAD transcription factors that regulate genes involved in cell proliferation, differentiation, apoptosis, and growth. Many advanced stage cancers are known to over-express TGFβ and TGFβR, promoting aggressive tumor formation. Inhibiting the TGFβ signaling pathway is a key therapeutic strategy in treating cancer. Enable your therapeutic programs by discovering small molecule inhibitors or biologics to TGFβR by using a robust and simple PathHunter TGFβR1/TGFβR2 Dimerization Assay. Analyze small molecule and biologics (antibody) receptor dimerization inhibitors and study compound toxicity profiles.

Wnt signaling plays a pivotal role in development, and it is implicated in a variety of disease states ranging from cancer to kidney and reproductive tract defects. Wnt ligands are associated with both β-Catenin dependent (canonical) and β-Catenin independent pathways. Analyze small molecules, siRNA, or functional antibodies that activate the frizzled (Fz) GPCR receptor and inhibit upstream GSK3β.