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DNA Damage Checkpoint
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ALX-350-290 Revised 18-Nov-08
Debromohymenialdisine
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SYNONYMS DBH
4-(2-Amino-4-oxo-2-imidazolin-5-ylidene)-4,5,6,7-tetrahydropyrrolo[2,3-c]azepin-8-one
PRODUCT LINE Natural Products / Antibiotics
PRODUCT CATEGORY Natural Products - Protein Kinase Inhibitors
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ALX-350-290-C100   100 µg 90.00 USD Add To Cart
Product Specification
FORMULA: C11H11N5O2
MW: 245.2
CAS NUMBER: 75593-17-8, 125118-55-0
SOURCE/HOST: Isolated from sponge Axinella carteri.
PURITY: ≥95% (HPLC)
APPEARANCE: Yellow solid.
SOLUBILITY: Soluble in 100% ethanol or DMSO.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
HANDLING: Protect from light. Keep under inert gas.
IDENTITY: Identity determined by 1H-NMR and MS.

Product Description
Inhibitor of G2 DNA damage checkpoint (IC50=8µM) and check point kinases 1 (Chk1) (IC50=3µM) and 2 (Chk2) (IC50=3.5µM) [1,3]. Unlike other checkpoint inhibitors DBH does not inhibit ataxia-telangiectasia mutated (ATM) or ATM-Rad3-related protein. Also inhibits MAP kinase kinase 1 (MEK-1) (IC50=881nM) but is not as potent as 10Z-hymenialdisine (Prod. No. ALX-350-289) (IC50=6nM) [2].
Product Specific Literature References
[1] Inhibition of the G2 DNA damage checkpoint and of protein kinases Chk1 and Chk2 by the marine sponge alkaloid debromohymenialdisine: D. Curman, et al.; J. Biol. Chem. 276, 17914 (2001) Abstract; Full Text
[2] Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1): D. Tasdemir, et al.; J. Med. Chem. 45, 529 (2002) Abstract
[3] G2 checkpoint abrogators as anticancer drugs: T. Kawabe; Mol. Cancer Ther. 3, 513 (2004) Abstract
Further Categories Containing This Product:
MAPK Pathway Inhibitors • Chk1 & Chk2 / Related Products • Natural Products for Cell Cycle Research • Alkaloids • Marine Natural Products
 
 
ALX-350-289 Revised 18-Nov-08
10Z-Hymenialdisine
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SYNONYMS 4-(2-Amino-4-oxo-2-imidazolin-5-ylidene)-2-bromo-4,5,6,7-tetrahydropyrrolo[2,3-c]azepin-8-one
PRODUCT LINE Natural Products / Antibiotics
PRODUCT CATEGORY Natural Products - Protein Kinase Inhibitors
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ALX-350-289-C500   500 µg 190.00 USD Add To Cart
ALX-350-289-M001   1 mg 340.00 USD Add To Cart
Product Specification
FORMULA: C11H10BrN5O2
MW: 324.1
CAS NUMBER: 82005-12-7
SOURCE/HOST: Isolated from sponge Axinella carteri.
PURITY: ≥97% (HPLC)
APPEARANCE: Yellow needles.
SOLUBILITY: Soluble in DMSO.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
HANDLING: Protect from light.
HAZARD: TOXIC.
IDENTITY: Identity determined by 1H- NMR and MS.

Product Description
Originally isolated from the sponges Axinella verrucosa and Acantella aurantiaca. Potent inhibitor of mitogen-activated protein kinase kinase-1 (MEK-1) (IC50=6nM). Blocks the in vivo phosphorylation of the microtubule-binding protein tau at sites that are hyperphosphorylated by glycogen synthase kinase-β (GSK-3β) and CDK5/p35 in Alzheimer’s disease. Inhibitor of DNA damage checkpoint at G2 phase (IC50=6µM), cyclin-dependent kinases CDK1/cyclin B (IC50=22nM), CDK2/cyclin A (IC50=70nM), CDK2/cyclin E (IC50=40nM), CDK4/cyclin D1 (IC50=600nM), CDK5/p25 (IC50=28nM), GSK-3β (IC50=10nM), and casein kinase 1 (CK1) (IC50=35nM). Inhibitor of NF-κB activation and of various pro-inflammatory cytokines such as IL-1, IL-2 (IC50=2.4µM), IL-6, IL-8, TNF-α (IC50=1.4µM) and nitric oxide (NO) (IC50=0.8µM) in a variety of cell lines.
Product Specific Literature References
Isolation and x-ray crystal structure of a novel bromo-compound from two marine sponges: G. Cimino, et al.; Tetrahedron Lett. 23, 767 (1982)
Bioactive alkaloids from the tropical marine sponge Axinella carteri: A. Supriyono, et al.; Z. Naturforsch. [C] 50, 669 (1995) Abstract
The natural product hymenialdisine inhibits interleukin-8 production in U937 cells by inhibition of nuclear factor-kappaB: J.J. Breton & M.C. Chabot-Fletcher; J. Pharmacol. Exp. Ther. 282, 459 (1997) Abstract; Full Text
Inhibition of NFkappaB-mediated interleukin-1beta-stimulated prostaglandin E2 formation by the marine natural product hymenialdisine: A. Roshak, et al.; J. Pharmacol. Exp. Ther. 283, 955 (1997) Abstract; Full Text
Inhibition of interleukin-1-induced proteoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine: A.M. Badger, et al.; J. Pharmacol. Exp. Ther. 290, 587 (1999) Abstract; Full Text
Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent: L. Meijer, et al.; Chem. Biol. 7, 51 (2000) Abstract
Inhibition of the G2 DNA damage checkpoint and of protein kinases Chk1 and Chk2 by the marine sponge alkaloid debromohymenialdisine: D. Curman, et al.; J. Biol. Chem. 276, 17914 (2001) Abstract; Full Text
An investigation of cell proliferation and soluble mediators induced by interleukin 1beta in human synovial fibroblasts: comparative response in osteoarthritis and rheumatoid arthritis: H. Inoue, et al.; Inflamm. Res. 50, 65 (2001) Abstract
Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1): D. Tasdemir, et al.; J. Med. Chem. 45, 529 (2002) Abstract
Inhibition of cytokine production by hymenialdisine derivatives: V. Sharma, et al.; J. Med. Chem. 47, 3700 (2004) Abstract
Further Categories Containing This Product:
CDK & Cyclin Inhibitors • MAPK Pathway Inhibitors • Natural Products - NF-kB Pathway Inhibitors • NF-kB Pathway Inhibitors • Natural Products for Cell Cycle Research • Alkaloids • Natural Products - Nitric Oxide Pathway Modulators • DNA Damage Checkpoint Other Products • GSK-3 Inhibitors • Marine Natural Products
 
 
ALX-804-229 Revised 11-Jan-07
Monoclonal Antibody to Rad9 (human) (93A535)
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PRODUCT LINE Cell Cycle
PRODUCT CATEGORY DNA Damage Checkpoint Other Products
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ALX-804-229-C100   100 µg 293.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
CLONE: 93A535
ISOTYPE: Mouse IgG1
CONCENTRATION: 0.5mg/ml
PURITY DETAIL: Protein G-affinity purified.
FORMULATION: Liquid. In PBS containing 0.2% gelatin and 0.05% sodium azide.
IMMUNOGEN: Recombinant human Rad9.
SPECIFICITY: Recognizes human Rad9. Detects a band of ~50kDa by Western blot.
APPLICATION: Immunocytochemistry (see [7])
Immunoprecipitation
Western Blot (1-2µg/ml)
SHIPPING: SHIPPED ON BLUE ICE
SHORT TERM STORAGE: +4°C
LONG TERM STORAGE: -20°C
USE/STABILITY: Stable for 6 months when stored at +4°C.
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Product Specific Literature References
[1] Cloning and sequence analysis of the Saccharomyces cerevisiae RAD9 gene and further evidence that its product is required for cell cycle arrest induced by DNA damage: R.H. Schiestl, et al.; Mol. Cell. Biol. 9, 1882 (1989) Abstract
[2] Characterization of RAD9 of Saccharomyces cerevisiae and evidence that its function acts posttranslationally in cell cycle arrest after DNA damage: T.A. Weinert & L.H. Hartwell; Mol. Cell. Biol. 10, 6554 (1990) Abstract
[3] A human homolog of the Schizosaccharomyces pombe rad9+ checkpoint control gene: H.B. Lieberman, et al.; PNAS 93, 13890 (1996) Abstract
[4] MEC1-dependent phosphorylation of Rad9p in response to DNA damage: A. Emili; Mol. Cell 2, 183 (1998) Abstract
[5] Human homologs of Schizosaccharomyces pombe rad1, hus1, and rad9 form a DNA damage-responsive protein complex: E. Volkmer & L.M. Karnitz; J. Biol. Chem. 274, 567 (1999) Abstract; Full Text
[6] The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1: R.P. St. Onge, et al.; Mol. Biol. Cell 10, 1985 (1999) Abstract
[7] Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-x L and promotes apoptosis: K. Komatsu, et al.; Nature Cell Biol. 2, 1 (2000) Abstract
General Information
Rad9 is a cell cycle checkpoint protein: DNA damage leads to extensive phosphorylation of Rad9 [4] which then inhibits progression from G2 in order to preserve cell viability, allowing proper ligation of DNA breaks before the entry of cells into mitosis [1,2]. The human homolog [3] of S. pombe Rad9 is physically proximal to the upstream (DNA damage) signal and associates with two other checkpoint control proteins, Rad1 and HHUS1 [5,6]. Rad9 also interacts with Bcl-2 family proteins Bcl-2 and Bcl-XL, but not with BAX or BAD. Overexpression of Rad9 in mammalian cells leads to apoptosis, where as antisense Rad9 RNA suppresses cell death induced by methyl methanesulphonate [7].
Further Categories Containing This Product:
DNA Replication Other Products • Monoclonal Antibodies
 
 
ALX-210-419 Revised 30-Oct-06
Polyclonal Antibody to 53BP1
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SYNONYMS anti-Tumor Protein p53 Binding Protein 1 PAb
anti-TP53BP1 PAb
anti-p202 PAb
PRODUCT LINE Cell Cycle
PRODUCT CATEGORY p53 Other Products
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ALX-210-419-R050   50 µl 180.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
Mouse
SOURCE/HOST: From rabbit.
FORMULATION: Liquid. Neat serum containing 0.05% sodium azide.
IMMUNOGEN: Recombinant human 53BP1 (tumor protein p53 binding protein 1) (aa 1308-1824).
SPECIFICITY: Recognizes native and denatured forms of full-length human 53BP1. Cross-reacts with mouse 53BP1.
APPLICATION: Immunocytochemistry (1:200);
Immunoprecipitation;
Western blot (1:2'000).
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: +4°C
USE/STABILITY: Storage at +4°C is recommended; if freezing is prefered add 50% glycerol.
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Product Description
The 53BP1 protein is implicated in the early response to DNA damage. The residues aa 1308-1824 are central to the antigen sequence recognized by the antibody ALX-210-419.
Product Specific Literature References
Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage: L. Anderson, et al.; Mol. Cell. Biol. 21, 1719 (2001) Abstract
Kinetochore localisation of the DNA damage response component 53BP1 during mitosis: D. Jullien, et al.; J. Cell Sci. 115, 71 (2002) Abstract; Full Text
Further Categories Containing This Product:
DNA Damage Checkpoint Other Products • Polyclonal Antibodies
 
 
ALX-210-803 Revised 09-Feb-05
Polyclonal Antibody to Ataxia telangiectasia Mutated (human)
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SYNONYMS anti-ATM (human) PAb
PRODUCT LINE DNA Regulation / Transcription
PRODUCT CATEGORY Ataxia telangiectasia Mutated / Related Products
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ALX-210-803-C100   100 µg 330.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
SOURCE/HOST: From rabbit.
CONCENTRATION: 0.1mg/ml
FORMULATION: 100µg of purified antibody in 1.0ml of 0.05M sodium phosphate buffer containing 0.1% sodium azide and 0.2% gelatin.
IMMUNOGEN: Synthetic peptide corresponding to aa 819-844 of human ATM (ataxia-telangiectasia mutated).
SPECIFICITY: Recognizes human ATM.
APPLICATION: Immunoprecipitation
Western Blot
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: +4°C
HANDLING: Do not freeze.
Product Description
Ataxia telangiectasia is a recesive childhood disease by mutations in the ATM (AT-mutated) gene. ATM protein and Ataxia telangiectasia and Rad3-related protein (ATR) belongs to a family of protein kinases that share similarities at their C-terminal region with the catalytic domain of PI(3)K (phosphoinositide 3-kinase). ATM and ATR function in response to DNA damage and repair as well as at DNA replication checkpoints during the cell cycle. ATM and ATR directly phosphorylate the breast/ovarian cancer susceptibility gene BRCA1 following DNA damage and also regulate Chk1, which is required for the G2/M checkpoint. Like DNA-PK ATR phosphorylates p53 on serine 15. ATM has also been shown to phosphorylate murine double minute 2 (MDM2) and to interact with histone deacetylase. ATM, but not ATR is cleaved during apoptosis very similar to PARP.
Product Specific Literature References
Ataxia-telangiectasia and cellular responses to DNA damage: M.S. Meyn; Cancer Res. 55, 5991 (1995) Abstract
Defective G2 checkpoint function in cells from individuals with familial cancer syndromes: R.S. Paules, et al.; Cancer Res. 55, 1763 (1995) Abstract
A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia: M.B. Kastan, et al.; Cell 71, 587 (1992) Abstract
Radiosensitivity in ataxia-telangiectasia: a new explanation: R.B. Painter & B.R. Young; PNAS 77, 7315 (1980) Abstract
The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species: K. Savitsky, et al.; Hum. Mol. Genet. 4, 2025 (1995) Abstract
A single ataxia telangiectasia gene with a product similar to PI-3 kinase: K. Savitsky, et al.; Science 268, 1749 (1995) Abstract
General Information
BACKGROUND/TECHNICAL INFORMATION Recommendations for Western blotting

ATM is a high MW protein of ~350kDa and as such, conditions may require optimization. 100-150µg of cell lysate is loaded on 5% acrylamide gels (until 200kDa marker is halfway through the gel) and transferred to nitrocellulose using semi-dry transfer at 9V constant voltage for 2 hours. Detection should be done using HRP-conjugated anti-rabbit IgG. This antibody may detect several smaller non-specific bands present in both ATM mutant and wild type cells. Therefore, careful titering of antibody concentrations is recommended.
Further Categories Containing This Product:
Polyclonal Antibodies
 
 
ALX-210-798 Revised 27-Dec-06
Polyclonal Antibody to ATR (human)
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SYNONYMS anti-Ataxia telangiectasia and Rad3-related Protein (human) PAb
PRODUCT LINE DNA Regulation / Transcription
PRODUCT CATEGORY Ataxia telangiectasia Mutated / Related Products
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ALX-210-798-R100   100 µl 379.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
SOURCE/HOST: From rabbit.
CONCENTRATION: 4mg/ml
FORMULATION: Liquid. Affinity purified IgG in PBS containing 0.05% sodium azide.
IMMUNOGEN: Recombinant human ATR (ataxia telangiectasia and Rad3-related protein) (aa 400-460).
SPECIFICITY: Recognizes human ATR. Detects a band of ~305kDa by Western blot.
APPLICATION: Immunoprecipitation
Western Blot (1:1'000)
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
HANDLING: Avoid freeze/thaw cycles.
Further Categories Containing This Product:
Polyclonal Antibodies
 
 
ALX-210-066 Revised 30-Oct-06
Polyclonal Antibody to ATRIP (human)
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SYNONYMS anti-ATR-interacting Protein (human) PAb
anti-ATM and Rad3-related Interacting Protein (human) PAb
anti-Ataxia telangiectasia and Rad3-related Interacting Protein (human) PAb
PRODUCT LINE DNA Regulation / Transcription
PRODUCT CATEGORY Ataxia telangiectasia Mutated / Related Products
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ALX-210-066-C050   50 µg 220.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
SOURCE/HOST: From rabbit.
CONCENTRATION: ~3.8mg/ml
FORMULATION: Liquid. Protein G purified antibody in PBS containing 10% glycerol and 0.02% sodium azide.
IMMUNOGEN: Recombinant human ATRIP (Ataxia telangiectasia and Rad3-related interacting protein) (aa 1-182).
SPECIFICITY: Recognizes human ATRIP.
APPLICATION: Immunohistochemistry
Immunoprecipitation (0.1-0.5µg)
Western Blot (0.75µg/ml)
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
HANDLING: Avoid freeze/thaw cycles.
Product Specific Literature References
ATR and ATRIP: partners in checkpoint signaling: D. Cortez, et al.; Science 294, 1713 (2001) Abstract
Further Categories Containing This Product:
Polyclonal Antibodies
 
 
ALX-201-233 Revised 22-Jun-07
Rad9/Rad1/Hus1 (human) (recombinant)
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SYNONYMS 9-1-1 Complex (human) (recombinant)
PRODUCT LINE Cell Cycle
PRODUCT CATEGORY DNA Damage Checkpoint Other Products
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ALX-201-233-C005   5 µg 240.00 USD Add To Cart
Product Specification
MW: 106kDa (heterotrimer of 43, 31 and 32kDa)
SOURCE/HOST: Produced in baculovirus.
CONCENTRATION: 1mg/ml
PURITY: ≥90% (by SDS-PAGE).
FORMULATION: Liquid. In 25mM Tris, pH 8.0, containing 20% glycerol, 100mM sodium chloride and 1mM β-mercaptoethanol.
SHIPPING: SHIPPED ON DRY ICE
LONG TERM STORAGE: -80°C
HANDLING: After opening, prepare aliquots and store at -80°C. Avoid freeze/thaw cycles.
Product Specific Literature References
The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilisation efficiency: implications for DNA repair: M. Toueille, et al.; Nucl. Acids Res. 32, 3316 (2004) Abstract; Full Text
The human checkpoint sensor and alternative DNA clamp Rad9-Rad1-Hus1 modulates the activity of DNA ligase I, a component of the long-patch base excision repair machinery: E. Smirnova, et al.; Biochem. J. 389, 13 (2005) Abstract
General Literature References
Regulation of the DNA replication fork: a way to fight genomic instability: M. Toueille and U. Hubscher; Chromosoma 113, 113 (2004) Abstract
Further Categories Containing This Product:
Recombinant Proteins / Fusion Proteins • DNA Replication Other Products
 
 
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