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New Members of the IL-1 (IL-1α/β, IL-18, IL-33) Family
ALX-522-127 IL-1F5 (human) (rec.)
ALX-522-128 IL-1F6 (human) (rec.)
ALX-522-129 IL-1F8 (human) (rec.)
ALX-522-130 IL-1F9 (human) (rec.)
IL-1F5, F6, F8 and F9 are new members of the IL-1 (IL-1α/β, IL-18, IL-33) family. IL-1F6, IL-1F8 and IL-1F9 activate the NF-κB and MAPK pathways through the IL-Rrp2 and IL-1RAcP receptor complex leading to the production of IL-6 and IL-8. Agonistic activation of the IL-1F6, F8 and F9 is counterbalanced by the inhibitory activity of IL-1F5. These interleukins are mainly expressed in skin keratinocytes and internal epithelial tissues exposed to pathogenic bacteria suggesting a role in immune signalling and inflammation. IL-F5, F6 and F9 as well as the receptor IL-1Rrp2 are increased in psoriasis.
LIT: Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2: R. Debets, et al.; J. Immunol. 167, 1440 (2001) • Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs: J.E. Towne, et al.; J. Biol. Chem. 279, 13677 (2004)
Related Product: MAb to IL-1F1 (mouse) (Flo1)
New BRCA2 Binding Protein Antibody
ALX-210-951 PAb to PALB2 (human) (AT126)
PALB2 (Partner and Localizer of BRCA2) is a new BRCA2 (a breast cancer susceptibility gene) binding protein. PALB2 colocalizes with BRCA2 in nuclear foci, promotes its stability in key nuclear structures (chromatin and nuclear matrix), and enables its recombinational repair and checkpoint functions. Mutations in the gene of PALB2 may contribute to breast cancer development (as well as prostate cancer) and cause Fanconi anemia.
LIT: Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2: B. Xia, et al.; Mol. Cell 22, 719 (2006) • Fanconi anemia is associated with a defect in the BRCA2 partner PALB2: B. Xia, et al.; Nat. Genet. 39, 159 (2007) • Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins: W. Wang; Nat. Rev. Genet. 8, 735 (2007) • The Fanconi anemia pathway and ubiquitin: C. Jacquemont & T. Taniguchi; BMC Biochem. 8 Suppl 1, S10 (2007) • PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene: N. Rahman, et al.; Nat. Genet. 39, 165 (2007)
Truncated Analog of α-Gal-Cer
ALX-306-029 OCH
OCH is a truncated analog of α-Gal-Cer. It selectively induces IL-4, as opposed to IFN-γ. OCH offers protection in mice against experimental autoimmune encephalomyelitis (EAE). Stimulation of NKT cells with α-Gal-Cer results in release of a mixture of Th1 and Th2 cytokines, stimulation with OCH results
in release of primarily Th2 cytokines.
LIT: Glycolipids for natural killer T cells: P. B. Savage, et al.; Chem. Soc. Rev. 35, 771 (2006) (Review)
Related Products: α-Gal-Cer / Gb3 / iGb3
New Glucose Uptake Modulater in Adipocytes
ALX-201-407 FGF-21 (human) (rec.) (His)
FGF-21 (Fibroblase Growth Factor 21) is a liver-derived endocrine factor that stimulates glucose uptake in adipocytes through activation of FGF receptors. Recent studies suggest that the expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPARα), a molecule which regulates the utilization of fat as an energy source during starvation. Thus, FGF-21 may play a role in diabetes and other metabolic diseases.
LIT: BetaKlotho is required for metabolic activity of fibroblast growth factor 21: Y. Ogawa, et al.; PNAS 104, 7432 (2007) • PPARalpha is a key regulator of hepatic FGF21: T. Lundasen, et al.; BBRC 360, 437 (2007) • Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21: H. Kurosu, et al.; J. Biol. Chem. 282, 26687 (2007)
Related Products: FGF-21 (mouse) (rec.) (His) / FGF-21 (human) (rec.) (FLAG) / FGF-21 (mouse) (rec.) (FLAG) / FGF-21 (human):Fc (human) (rec.) / FGF-21 (mouse):Fc (human) (rec.) / PAb to FGF-21 (human) / PAb to FGF-21 (mouse)
Notch 1 Ligand
ALX-201-390 Jagged-1 (human):Fc (human) (rec.)
The Notch family of proteins are involved in the regulation of key biological processes such as cell fate determination, proliferation differentiation and apoptosis. Jagged-1 (JAG1; HJ1; CD339), a cell surface glycoprotein, is one of several ligands that activate multiple Notch receptors and is involved in mediating Notch signalling. Jagged-1 signalling through notch 1 has been shown to play a role in hematopoiesis. Jagged-1 also seems to be involved in early and late stages of mammalian cardiovascular development and has been shown to enhance fibroblast growth factor-induced angiogenesis (in vitro). Jagged-1 overexpression has been reported in many glioma cell lines and seems to be critical for glioma cell survival and proliferation. Mutations in the human Jagged-1 gene cause Alagille syndrome.
LIT: An antisense oligonucleotide to the notch ligand jagged enhances fibroblast growth factor-induced angiogenesis in vitro: A.B. Zimrin, et al.; J. Biol. Chem. 271, 32499 (1996) • Mutations in the human Jagged1 gene are responsible for Alagille syndrome: T. Oda, et al.; Nat. Genet. 16, 235 (1997) • Familial Tetralogy of Fallot caused by mutation in the jagged1 gene: Z.A. Eldadah, et al.; Human Mol. Genet. 10, 163 (2001) • Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling: S.E. Bell, et al.; J. Cell Sci. 114, 2755 (2001) • Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation: B.W. Purow, et al.; Cancer Res. 65, 2353 (2005) • Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes: H. Li, et al.; BBRC 341, 320 (2006)
Related Products: DLL1 (human) (rec.) / PAb to DLL1 (human) / DLL4 (human):Fc (human) (rec.)
New Cancer Markers
ALX-803-318 MAb to RUNX3 (human) (R3-6E9)
ALX-803-319 MAb to RUNX3 (human) (R3-5G4)
ALX-803-320 MAb to RUNX3 (R3-1E10)
RUNX3 [Runt-related Transcription Factor 3], a novel tumor suppressor, upregulates Bim in gastric epithelial cells undergoing transforming growth factor β-induced apoptosis. It is frequently inactivated in gastric cancer by protein mislocation.
LIT: RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization: K. Ito, et al.; Cancer Res. 65, 7743 (2005) • RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer: Q.C. Lau, et al.; Cancer Res. 66, 6512 (2006) • The RUNX3 tumor suppressor upregulates Bim in gastric epithelial cells undergoing transforming growth factor beta-induced apoptosis: T. Yano, et al.; Mol. Cell. Biol. 26, 4474 (2006)
Wide Panel of PI(3)K Inhibitors
Selective PI(3)K p110α Isoform Inhibitor
ALX-270-455 Compound 15e
Potent and specific inhibitor of phosphoinositide 3-kinase p110α isoform. Inhibits proliferation of A375 melanoma cells (IC50=0.58µM).
LIT: Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110alpha inhibitors: M. Hayakawa, et al.; Bioorg. Med. Chem. 14, 6847 (2006)
Selective PI(3)K p110β Isoform Inhibitor
ALX-270-464 TGX-221
Potent, selective and cell permeable inhibitor of phosphoinositide 3-kinase (PI(3)K) p110β.
LIT: Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils: A.M. Condliffe, et al.; Blood 106, 1432 (2005) • PI 3-kinase p110beta: a new target for antithrombotic therapy: S.P. Jackson, et al.; Nat. Med. 11, 507 (2005)
Selective PI(3)K p110γ Isoform Inhibitors
ALX-270-465 AS-252424
LIT: Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils: A.M. Condliffe, et al.; Blood 106, 1432 (2005) • Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase gamma: V. Pomel, et al.; J. Med. Chem. 49, 3857 (2006)
ALX-270-461 AS-604850
LIT: Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis: M. Camps, et al.; Nat. Med. 11, 936 (2005) • Key role of the p110delta isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110delta function in B cells: A. Bilancio, et al.; Blood 107, 642 (2006)
ALX-270-462 AS-605240
LIT: Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis: M. Camps, et al.; Nat. Med. 11, 936 (2005) • PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus: D.F. Barber, et al.; Nat. Med. 11, 933 (2005)
PI(3)K Inhibitor with an Interesting Profile
ALX-270-460 PI-103
Potent, cell permeable and ATP-competitive inhibitor of DNA-PK, phosphoinositide 3-kinase (PI(3)K), the rapamycin-sensitive (mTORC1), and rapamycin-insensitive (mTORC2) complexes of the protein kinase mTOR. Exhibits little activity towards a panel of more than 40 other kinases even at concentrations as high as 10µM. Effectively blocks cell proliferation in glioma cell lines both in vitro and in vivo.
LIT: A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma: Q.W. Fan, et al.; Cancer Cell 9, 341 (2006) • A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling: Z.A. Knight, et al.; Cell 125, 733 (2006)
New Inflammasome (NALP) Modulator Antibody
ALX-210-949 PAb to Pannexin-1 (human)
Pannexin-1 belongs to a new family of membrane proteins with homology to the invertebrate gap junction proteins innexins. Pannexin-1 has recently been involved in the NALP (inflammasome)-mediated caspase-1 activation and IL-1β.
LIT: Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling: T.D. Kanneganti, et al.; Immunity 26, 433 (2007)
Inhibitor of G9a Histone Methyltransferase
ALX-210-473 BIX 01294
Selective and cell permeable inhibitor of G9a histone methyltransferase.
LIT: Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase: S. Kubicek, et al.; Mol. Cell 25, 473 (2007)
