Assays & Kits

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.

PARP1, also known as poly-(ADP-ribose) polymerase 1 or NAD⁺ ADP-ribosyltransferase 1, is part of the PARP family, and it is the most abundant member.  ADP ribosylation, which is the addition of an ADP-ribose to a protein, is a reversible post-translational modification of proteins mostly involved in the DNA Damage Response (DDR) pathway. Poly-ADP-ribosylation (termed PARylation) is the addition of linear or branched chains of ADP-ribose. PARP1 participates in DNA repair by non-homologous end joining (NHEJ), homologous recombination (HR), microhomology-mediated end-joining (MMEJ) and nucleotide excision repair. Dysfunction of DDR pathways can lead to oncogenesis. Overexpression of PARP1 has been found in breast and colon cancer, neuroblastoma, and others. This overexpression can lead to increasing MMEJ, an error-prone DNA repair mechanism, and genome instability leading to cancer. In addition to being involved in DDR, PARP1 is also linked to inflammation and type I diabetes.

PARP2, also known as poly-(ADP-ribose) polymerase 2 or NAD⁺ ADP-ribosyltransferase 2, is part of the PARP family. ADP ribosylation, which is the addition of an ADP-ribose to a protein, is a reversible post-translational modification of proteins mostly involved in the DNA Damage Response (DDR) pathway. Poly-ADP-ribosylation (termed PARylation) is the addition of linear or branched chains of ADP-ribose. PARP2 participates in DNA repair (only 10% of total PARP activity is due to PARP2), but also in oxidative stress and mitochondrial fragmentation. Dysfunction of the DDR and oxidative stress pathways can lead to oncogenesis. Genetic ablation of PARP2 has indicated roles of PARP2 in adipogenesis, spermatogenesis and thymocyte survival. It is also a co-factor of nuclear receptors like ER (estrogen receptor) and PPAR (peroxisome proliferator-activated receptors). PARP2 is overexpressed in prostate cancer and may contribute to the disease through the FOXA1 (forkhead box protein A1)/

The CDK12/CyclinK complex comprises human CDK12 (cyclin dependent kinase 12) and human cyclinK. CDK12 is ubiquitously expressed, being present at high levels in the reproductive tissues, endocrine tissues, bone marrow and lymph nodes, predominantly in the nucleus of cells. CDK12 is involved in gene expression, transcription elongation and genome stability. CDK12 binds only to cyclinK, and the formation of this complex seems important to maintain cyclinK stability. This complex regulates phosphorylation of serine 2 in the C-terminal domain of RNA polymerase II, which is responsible for transcriptional elongation and synthesis of full-length mature mRNAs. However, lack of CDK12 seems to only affect about 5% or less of the total transcription, indicating a selective role of this complex in the transcription of certain genes. The use of inhibitors, such as THZ531, indicated that the genes being selectively regulated by CDK12/cyclinK are the core DDR (DNA damage and repair) genes. CDK12 pla

Bruton€™s tyrosine kinase or BTK, is a non-receptor kinase protein found in hematopoietic and plasma cells. It is involved in functionality, maturation, and apoptosis of B cells, in addition to regulating signals in the MAPK (mitogen-activated protein kinase), PI3K (phosphoinositide 3-kinase) and NF-κB (nuclear factor kappa B) pathways. The BTK pathway has implications for a number of autoimmune disorders including isolated growth hormone deficiency type III and rheumatoid arthritis. BTK inhibitors have been used in the treatment of inflammatory diseases and hematological disorders including cancer. For instance, Ibrutinib (also known as PCI-32765), is used in the clinic for the treatment of CLL (chronic lymphocytic leukemia), MCL (mantle cell lymphoma) and GvHD (graft versus host disease) and other diseases. However, low-selectivity BTK inhibitors have severe side effects, so further refinement is necessary. Development of highly selective BTK inhibitors will lead to greater benefits

Protein Mixed Lineage Leukemia-1 (MLL1, also known as KMT2A) belongs to the SET1/MLL family which consists of six (MLL1-4/KMT2A-2D, SET1A/KMT2F, and SET1B/KMT2G) major methyltransferases in mammals. MLL1 is a histone-H3 lysine-4 (H3K4) methyltransferase that promotes H3K4 mono-/di-/tri-methylation, a conserved trait of euchromatin associated with transcriptional activation. MLL1 is a master regulator for the transcription of many important genes including homeobox (Hox), which has been implicated in hematopoiesis and embryonic development. MLL1 forms a complex with RbBP5 (retinoblastoma-binding protein 5), ASH2L (Absent, small, homeotic disks-2-like), WDR5 (WD40 repeat-containing protein 5), and DPY30 (DumPY protein 30) to catalyze tri-methylation of H3K4. WDR5 represents a therapeutically exploitable target for cancer treatment as it plays a crucial role in MLL1 complex assembly and disassembly. WDR5 has two protein interaction sites: the WDR5-interacting (WIN) binding site and the WD

The Mixed Lineage Leukemia-4 (MLL4, also known as KMT2B) protein belongs to the SET1/MLL family which consists of six (MLL1-4/KMT2A-2D, SET1A/KMT2F, and SET1B/KMT2G) major methyltransferases in mammals. MLL4 is a histone-H3 lysine-4 (H3K4) methyltransferase that promotes H3K4 mono-/di-/tri-methylation, a conserved trait of euchromatin associated with transcriptional activation. MLL4 is a critical player in memory formation. MLL4 forms a complex with RbBP5 (retinoblastoma-binding protein 5), ASH2L (Absent, small, homeotic disks-2-like), WDR5 (WD40 repeat-containing protein 5), and DPY30 (DumPY protein 30) to catalyze methylation of H3K4. WDR5 represents a therapeutically exploitable target for cancer treatment as it plays a crucial role in MLL1 complex assembly and disassembly. WDR5 has two protein interaction sites: the WDR5-interacting (WIN) binding site and the WDR5-binding-motif (WBM) site. MLL1-4 forms the complex via WIN binding site, while RbBP5 is bound to WBM site, which is als

EGFR (epidermal growth factor receptor), also known as ERBB-1 and HER1, is the cell-surface tyrosine kinase receptor for members of the epidermal growth factor family. Its ligands include EGF, TGFα (transforming growth factor alpha), HB-EGF (heparin-binding EGF), betacellulin, amphiregulin, epiregulin and epigen. EGFR exists as an inactive monomer until it gets activated. Upon ligand binding it forms an asymmetric dimer, for instance with HER2 (human epidermal growth factor receptor 2), which induces autophosphorylation, creating binding sites for adaptor proteins such as GRB2 (growth factor receptor-bound protein 2) and/or CBL (Casitas B-lineage lymphoma). EGFR can bind to several adaptor proteins simultaneously and thus activate multiple positive and negative signaling pathways. Overexpression and/or hyperactivation of EGFR kinase is associated with several human cancers such as lung, glioblastoma (GBM), and epithelial tumors of the neck and head, being the most common mutation in GB