Functional Assays

Sandwich TR-FRET immunoassay for the quantitative measurement of human CCL17 (C-C motif chemokine 17; CC chemokine TARC) in cell culture supernatants. The kit does not include a recombinant human CCL17/TARC standard, which must be purchased separately from R&D Systems® (catalog number 364-DN).

DR3 (death receptor 3), also known as tumor necrosis factor receptor superfamily member 25 or TNFRSF25, is a membrane receptor of the tumor necrosis factor receptor superfamily of proteins (TNFRSF), which associates with TL1A (TNF-like protein 1A) in T and NK cells. DR3 has been recognized as a significant anti-apoptotic and differentiation factor and it is a co-stimulatory receptor. TL1A, also called TNFSF15, is a member of the tumor necrosis factor family. It is expressed in different immune cells, such as monocyte, macrophage, dendritic cell, T cell and non-immune cells. TL1A competitively binds to DR3, having a higher affinity for DcR3 (decoy receptor 3), providing stimulatory signal for downstream signaling pathways. It then regulates proliferation, activation, apoptosis, and chemokine production in effector cells. The role of DR3 in T cell activation, and consequently in cytokine secretion and cell proliferation, makes it an attractive target in cancer therapy. Inhibition of DR3-

DR3 (death receptor 3), also known as tumor necrosis factor receptor superfamily member 25 or TNFRSF25, is a membrane receptor of the tumor necrosis factor receptor superfamily of proteins (TNFRSF), which associates with TL1A (TNF-like protein 1A) in T and NK cells. DR3 has been recognized as a significant anti-apoptotic and differentiation factor and it is a co-stimulatory receptor. TL1A, also called TNFSF15, is a member of the tumor necrosis factor family. It is expressed in different immune cells, such as monocyte, macrophage, dendritic cell, T cell and non-immune cells. TL1A competitively binds to DR3, having a higher affinity for DcR3 (decoy receptor 3), providing stimulatory signal for downstream signaling pathways. It then regulates proliferation, activation, apoptosis, and chemokine production in effector cells. The role of DR3 in T cell activation, and consequently in cytokine secretion and cell proliferation, makes it an attractive target in cancer therapy. Inhibition of DR3-

ACHE (acetylcholinesterase), also known as AChase or acetylhydrolase, is known to hydrolyze acetylcholine (ACh), a naturally occurring neurotransmitter, into acetic acid and choline. It is a highly effective hydrolase, with an activity near the limit of substrate diffusion. It can be found in motor and sensory neurons, and it is involved in the termination of impulse transmission, by being located on the post-synaptic membrane and hydrolyzing Ach. Ach can be taken up by and used to synthesize acetyl-Coa again in a reaction catalyzed by choline acetyltransferase. ACHE can exist in different molecular forms, which have different expression patterns. It has been known for many years that AD (Alzheimer€™s disease) patients have an abnormal distribution of these molecular forms, with an increase in the light forms versus G4 molecules. P-tau can lead to higher expression of T-ACHE, and ACHE may play a role in formation of beta-amyloid plaques. Inhibitors of ACHE result in high concentrations

ERK1 (extracellular signal-regulated kinase 1) is also known as mitogen-activated protein kinase 3 (MAPK3),  is a dual serine/threonine and tyrosine kinase. ERK (extracellular signal-regulated kinases), also known as classical MAPK (mitogen-activated protein kinases), are protein kinases involved in crucial intracellular signaling pathways, and regulate processes like mitoses, meiosis, and other functions. In the MAPK/ERK pathway Ras proteins are activated by several external molecules, including cytokines and viruses. These are followed by an activation cascade of c-Raf, MEK (mitogen-activated protein kinase kinase) and finally ERK. ERK1/2 in turn activates transcription factors. Disruption of the MAPK/ERK pathway at any point results in cancer. Inhibitors for Ras, Raf and MEK have been developed and result in rapid tumor reductions. However, resistance to treatment and relapse are quite frequent. This has led the field to focus on the development of ERK inhibitors, although these are

The Notch (neurogenic locus notch homolog protein) signaling is evolutionally highly conserved and implicated in various aspects of cancer development and progression. Aberrant activation of Notch1 signaling, often through mutations or overexpression, is associated with several types of cancer, including leukemia, breast cancer, lung cancer, and others. DLL4 (delta like canonical notch ligand 4), as a ligand of Notch receptors, can also influence tumor angiogenesis, promoting the growth of blood vessels within tumors and facilitating tumor progression. As Notch1 and DLL4 signaling pathway plays significant roles in cancer development, several Notch1 and DLL4 neutralizing antibodies have been evaluated in preclinical studies and clinical trials across various cancer types.

CD200 (Cluster of Differentiation 200) and its receptor, CD200R, are cell surface proteins that play a crucial role in immune regulation and tolerance. The CD200-CD200R pathway is primarily involved in inhibiting immune responses, helping to maintain immune homeostasis and prevent excessive inflammation. In many cancers, tumor cells overexpress CD200, which interacts with CD200R on immune cells, particularly myeloid cells like macrophages and dendritic cells. This interaction leads to the suppression of immune responses against the tumor, effectively promoting immune evasion. Neutralizing antibodies against CD200 or CD200R can block this interaction, preventing the inhibitory signal from being delivered to immune cells. As a result, the anti-tumor immune response is enhanced, leading to improved recognition and elimination of tumor cells by the immune system. The development of strategies targeting this complex holds great potential in cancer therapy.

Cereblon is the substrate-binding component of the E3 protein ligase complex Cereblon-CUL4A (cullin-4A)-RBX1 (RING-box protein 1) that targets proteins for degradation through the proteasome system. The binding of Cereblon to a substrate protein engages the E3 ligase activity of the complex and results in the ubiquitination and ultimate degradation of the substrate protein. PROTACs are bifunctional molecules that bring together a therapeutic target and an E3 ligase to promote the ubiquitination and ultimately the degradation of the target. Efficiency of ubiquitination is an important factor for optimization of heterobifunctional degraders. BRD3, also known as RING3L (RING3-like protein) belongs to the BET family of proteins and is involved in transcription by associating with acetylated lysines present in histones and transcription factors. Chromosomal translocations of BRD3 with NUT (nuclear protein in testis) can lead to cancer, and it has been shown that the use of BET inhibitors or

FGR is a tissue-specific member of the Src tyrosine kinase family of proteins, and it is involved in Fcγ receptor signaling pathways in phagocytosis and mitochondrial oxidative phosphorylation. This protein is overexpressed in several cancer types, such as AML (acute myeloid leukemia), and has also been linked to Alzheimer€™s disease (AD), Parkinson€™s disease (PD), pain, diabetes, and schizophrenia. Activation of the FGR/SIRT1 (sirtuin 1)/PGC-1α (peroxisome proliferator-activator receptor γ coactivator 1α) pathway may also be involved in sepsis. Interestingly, it has been found that obesity can lead to FGR activation in macrophages, and contribute to inflammation, making the development of strategies targeting the mitochondrial ROS (reactive oxidative species)- FGR axis clinically relevant in obesity. A deeper understanding of the role of this protein in health and disease will open new therapeutic avenues for several FGR linked disorders.