A natural inhibitor of NOD2 and NF-κB signaling

Parthenolide is a sesquiterpene lactone from the plant feverfew (T. parthenium). It inhibits the growth of the promastigote form of L. amazonensis (IC₅₀ = 3.6 μg/ml). Parthenolide also induces apoptosis in cancer cells, at least in part by inhibiting NF-κB- and STAT-mediated anti-apoptotic gene transcription. This compound has also been shown to block inflammation by inhibiting signaling through NF-κB. Inhibition of NF-κB by parthenolide can be achieved by direct binding of the pattern recognition receptor NOD2 by parthenolide.

For immunochemical analysis of Rb

Antigen: synthetic peptide corresponding to a region of the caspase-3-induced cleavage site of human Rb · Clone designation: 172C1094 · Host: mouse · Application(s): WB and IHC · The retinoblastoma gene product (Rb) is a tumor suppressor protein and acts as cell cycle regulator. Recently, Rb has been shown to play a role in apoptosis. During apoptosis, Rb is subjected to cleavage by a caspase-3 like protease. Caspase-3 cleaves Rb into 48 and 68kDa fragments.{19626-19628} Cleavage of Rb would make it functionally inactive, causing release of E2F-1. The E2F-1 then may promote apoptosis. The antibody recognizes cleaved Rb. The antibody does not recognize full-length Rb.

A DNA-binding anti-tumor antibiotic

Mithramycin A is a DNA-binding, anti-tumor and neuroprotective antibiotic originally isolated from S. grieseus that has long been used as a chemotherapeutic agent. It mediates its protective function, in part, by regulating acetylation of histones or transcription factors and, thereby, chromatin accessibility to transcriptional machinery. As a selective Sp1 inhibitor, mithramycin A binds to GC rich DNA sequences, displacing Sp1 transcription factor binding to oncogene promoters, which inhibits their expression. Mithramycin A (at 10-200 nM) can sensitize tumor cells to TRAIL-induced apoptosis and has been used to selectively target tumor cells in many different cancer models.

A high-affinity ligand for retinoid X receptors

Bexarotene is a high-affinity ligand for retinoid X receptors (RXRs) (EC₅₀ = 28, 25, and 20 nM for RXRα, β, and γ, respectively). It inhibits cell cycle progression, induces apoptosis, prevents or overcomes multidrug resistance through multidrug resistance protein 1 (MDR1), and blocks angiogenesis and metastasis, making it a promising chemopreventive agent against cancer. Bexarotene also, through RXR activation, stimulates clearance of soluble β-amyloid, reduces plaque area, and reverses deficits related to Alzheimer’s disease in mice.

Inhibitor of acid sphingomyelinase

Sphingomyelinases catalyze the degradation of cellular sphingomyelin to phosphorylcholine and ceramide. Acid sphingomyelinase has vacuolar activity that is important in a variety of physiological and pathophysiological processes. 1-Aminodecylidene bis-phosphonic acid (sodium salt) is a potent inhibitor of acid sphingomyelinase (IC₅₀ = 20 nM). It completely inhibits dexamethasone-induced apoptosis in HepG2 cells, presumably by preventing the generation of proapoptotic ceramide. This compound is more than 5,000 times more selective for acid sphingomyelinase than for the Mg2+-dependent neutral sphingomyelinase (IC₅₀ > 100 μM).

Natural vasorelaxant and inhibitor of EGFRs and HATs

Delphinidin chloride is an anthocyanidin, a natural plant pigment which serves as the precursor of certain anthocyanins that provide the blue-red colors of flowers, fruits, and red wine. Delphinidin induces the release of nitric oxide by vascular endothelium, causing vasorelaxation. It also inhibits signaling through epithelial growth factor receptors, suppressing the expression of estrogen receptor α and inducing both apoptosis and autophagy at a dose of 1-40 μM. Delphinidin also inhibits the histone acetyltransferase activities of p300/CBP (IC₅₀ ~ 30 μM).

A mitochondrial F1F0-ATP synthase inhibitor

Oligomycins are macrolides created by Streptomyces species that can be toxic to other organisms. Different oligomycin isomers are highly specific for the disruption of mitochondrial metabolism. Oligomycin A, a dominant analog of the isomers, is an inhibitor of mitochondrial F1F0-ATP synthase that induces apoptosis in a variety of cell types (average GI₅₀ = 270 nM). Oligomycin A exhibits antifungal, antitumor, and nematocidal activities, but has poor solubility in water and other biocompatible solvents, which limits its clinical application.

A mycotoxin that disrupts microtubule organization

Citrinin is a mycotoxin originally isolated from P. citrinum that is also produced by a variety of other fungi that are found as contaminants in human foodstuffs and animal feeds. Citrinin exerts cytotoxic and genotoxic effects in various mammalian cells, causing mycotoxic nephropathy in livestock and Balkan nephropathy and yellow rice fever in humans. Because citrinin induces apoptosis and blocks tubulin polymerization as well as mitotic spindle assembly, it is useful as a biological research reagent.

An antibiotic that inhibits protein and DNA synthesis

Anisomycin is a pyrrolidine antibiotic produced by S. griseolus that inhibits protein and DNA synthesis. It activates stress-activated protein kinase, MAP kinase, and other signal transduction pathways. At 30 mg/kg, anisomycin displays immunosuppressive activity superior to that of Cyclosporine A, blocking T cell proliferation in skin-transplanted mice. Through a caspase-8-dependent pathway, anisomycin acts as a potent and specific anoikis sensitizer of malignant epithelial cells resistant to apoptosis upon detachment from the ECM, preventing distal tumor formation in a mouse model of prostate cancer metastases.

A side-chain substituted oxysterol

25-hydroxy Cholesterol is a side-chain substituted oxysterol derived from dietary cholesterol that inhibits the cleavage of sterol regulatory element binding proteins (SREBPs) to suppress endogenous cholesterol synthesis in various cell types. It has been implicated in a variety of metabolic events including cholesterol homeostasis and atherosclerosis as well as antitumor activities as it has been shown to induce apoptosis through down-regulation of Bcl-2 expression and activation of caspases. Immunomodulating capabilities have also been observed as the oxysterol can act as a LXR-RXR ligand coupling cholesterol synthesis to T cell proliferation, can reduce (EC₅₀ ~ 65 nM) IgA production by B cells in response to IL-2, and can suppress differentiation of monocytes into macrophages.

An internal standard for the quantification of 25-hydroxy cholesterol

25-hydroxy Cholesterol contains six deuterium atoms at the 26, 26, 26, 27, 27, and 27 positions. It is intended for use as an internal standard for the quantification of 25-hydroxy cholesterol by GC- or LC-mass spectrometry. 25-hydroxy Cholesterol is a side-chain substituted oxysterol derived from dietary cholesterol that inhibits the cleavage of sterol regulatory element binding proteins (SREBPs) to suppress endogenous cholesterol synthesis in various cell types. It has been implicated in a variety of metabolic events including cholesterol homeostasis and atherosclerosis as well as antitumor activities as it has been shown to induce apoptosis through down-regulation of Bcl-2 expression and activation of caspases. Immunomodulating capabilities have also been observed as the oxysterol can act as a LXR-RXR ligand coupling cholesterol synthesis to T cell proliferation, can reduce (EC₅₀ ~ 65 nM) IgA production by B cells in response to IL-2, and can suppress differentiation of monocytes into macrophages.

For immunochemical analysis of HMGB1 (Clone IMG19N10B7)

Antigen: full-length recombinant human HMGB1 · Clone designation: IMG19N10B7 · Host: mouse · Isotype: IgG2bĸ · Application(s): FC, IHC (paraffin), and WB · High Mobility Group Protein B₁ (HMGB1) belongs to the HMGB family and contains two HMG box DNA-binding domains. It is a highly conserved, ubiquitous protein present in the nuclei and cytoplasm of nearly all cell types, and is a necessary and sufficient mediator of inflammation during sterile and infection-associated responses. HMGB1 also act as DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). It is reported that the level of HMGB1 is elevated during sterile tissue injury, infection, lethal endotoxemia or sepsis, collagen-induced arthritis, and ischemia-reperfusion induced tissue injury.

For immunochemical analysis of HMGB1

Antigen: full-length recombinant human HMGB1 · Clone designation: IMG19N15F4 · Host: mouse · Isotype: IgG1ĸ · Application(s): FC, IHC (paraffin), and WB · High Mobility Group Protein B₁ (HMGB1) belongs to the HMGB family and contains two HMG box DNA-binding domains. It is a highly conserved, ubiquitous protein present in the nuclei and cytoplasm of nearly all cell types, and is a necessary and sufficient mediator of inflammation during sterile and infection-associated responses. HMGB1 also act as DNA nuclear binding protein that has been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). It is reported that the level of HMGB1 is elevated during sterile tissue injury, infection, lethal endotoxemia or sepsis, collagen-induced arthritis, and ischemia-reperfusion induced tissue injury.

For immunochemical analysis of p53DINP1

Antigen: Synthetic peptides from human p53DINP1 · Host: Rabbit · Application(s): WB · A novel p53 inducible gene was identified and designated p53DINP1 (for p53-dependent damage-inducible nuclear protein). p53DINP1 may regulate p53-dependent apoptosis through phosphorylation at Ser⁴⁶ and induction of p53AIP1. p53DINP1/SIP is expressed in many tissues and induced by a variety of stress agents including UV stress, mutagenic stress, heat shock, and oxidative stress.

An inhibitor of ETS family transcription factors

Ewing’s sarcoma is characterized by the formation of an oncogenic fusion protein, EWS-FLI1, which binds to RNA helicase A. YK-4-279 binds to EWS-FLI1 (K_d = 9.48 μM), blocking the interaction of EWS-FLI1 and RNA helicase and driving apoptosis in Ewing’s sarcoma family tumors. Through these effects, YK-4-279 reduces the growth of Ewing’s sarcoma orthotopic xenografts. Importantly, it is effective in Ewing’s sarcoma cells, both in vitro and in vivo, that are chemotherapy-resistant. YK-4-279 also binds the ETS transcription factors ERG and ETV1 (K_d = 11.7 and 17.4, respectively), which form fusion proteins that contribute to some types of prostate cancer. (−)-YK-4-279 is a highly purified enantiomer of YK-4-279. Its properties have not been characterized.

An inhibitor of ETS family transcription factors

Ewing’s sarcoma is characterized by the formation of an oncogenic fusion protein, EWS-FLI1, which binds to RNA helicase central to disease. YK-4-279 binds to EWS-FLI1 (K_d = 9.48 μM), blocking the interaction of EWS-FLI1 and RNA helicase and driving apoptosis in Ewing’s sarcoma family tumors. Through these effects, YK-4-279 reduces the growth of Ewing’s sarcoma orthotopic xenografts. Importantly, it is effective in Ewing’s sarcoma cells, both in vitro and in vivo, that are chemotherapy-resistant. YK-4-279 also binds the ETS transcription factors ERG and ETV1 (K_d = 11.7 and 17.4, respectively), which form fusion proteins that contribute to some types of prostate cancer. (+)-YK-4-279 is a highly purified enantiomer of YK-4-279. Its properties have not been characterized.

Active, pure human recombinant enzyme

Source: recombinant C-terminal FLAG-tagged protein expressed in E. coli · M_r: 76.3 kDa · TNF Receptor-Associated Protein 1 (TRAP1) is a mitochondrial protein that plays a role in maintaining mitochondrial function and regulating cell apoptosis as a pro-survival protein. TRAP1 was initially identified as an interacting protein that binds to the intracellular domain of TNF-α Receptor 1 (TNFR1) in vitro. TRAP1 is a member of the Heat Shock Protein 90 (HSP90) family that possess ATPase activity. TRAP1 has been seen to be upregulated in tumor cells and failure of anticancer drug treatment in cells has been associated with increased levels of TRAP1, which is thought to elicit a pro-survival pathway in cells. Increased expression of TRAP1 in cardiomyocytes induced by hypoxic stress plays a protective role by regulating the opening of the mitochondrial permeability transition pore. Geldanamycin is a naturally occuring inhibitor that binds to the ATP binding site of TRAP1 and inhibits its activity. The small molecule inhibitor SNX-0723 also binds and inhibits TRAP1. Both inhibitors have binding dissociation constants (K_d) of 1-2 μM.