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MAP Kinase Pathways
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ALX-380-116 Revised 07-Apr-08
Hypothemycin
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PRODUCT LINE Natural Products / Antibiotics
PRODUCT CATEGORY Antibiotics - Antifungal
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ALX-380-116-C250   250 µg 140.00 USD Add To Cart
ALX-380-116-M001   1 mg 420.00 USD Add To Cart
Product Specification
FORMULA: C19H22O8
MW: 378.4
CAS NUMBER: 76958-67-3
SOURCE/HOST: Isolated from Phoma sp.
PURITY: ≥98% (HPLC)
APPEARANCE: Off-white solid.
SOLUBILITY: Soluble in DMSO or acetone; insoluble in methanol or water.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C

Product Description
Exhibits antifungal and cytotoxic activity against some tumor cell lines partly attributed to inhibition of Ras-inducible genes. Inhibits proliferation of mouse and human T cells and modulates production of cytokines during T cell activation. Facilitates the ubiquitinylation process of cyclin D1. Has been identified as a potent and selective inhibitor of threonine/tyrosine-specific kinase, MEK, and other protein kinases that contain a conserved cysteine residue in the ATP-binding site in both in vitro and in vivo studies.
Product Specific Literature References
Metabolites of pyrenomycetes XIII: Structure of (+) hypothemycin, an antibiotic macrolide from hypomyces trichothecoides: M.S.R. Nair & S.T. Carey; Tetrahedron Lett. 21, 2011 (1980)
Metabolites of pyrenomycetes. XIV: Structure and partial stereochemistry of the antibiotic macrolides hypothemycin and dihydrohypothemycin: M.S.R. Nair, et al.; Tetrahedron 37, 2445 (1981)
Revised structure and stereochemistry of hypothemycin: T. Agatsuma et al.; Chem. Pharm. Bull. 41, 373 (1993)
Antitumor efficacy of hypothemycin, a new Ras-signaling inhibitor: H. Tanaka, et al.; Jpn. J. Cancer Res. 90, 1139 (1999) Abstract
Hypothemycin inhibits the proliferative response and modulates the production of cytokines during T cell activation: R. Camacho, et al.; Immunopharmacology 44, 255 (1999) Abstract
Suppression of oncogenic transformation by hypothemycin associated with accelerated cyclin D1 degradation through ubiquitin-proteasome pathway: H. Sonoda, et al.; Life Sci. 65, 381 (1999) Abstract
Resorcylic acid lactones: naturally occurring potent and selective inhibitors of MEK: A. Zhao, et al.; J. Antibiot. 52, 1086 (1999) Abstract
Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides: A. Schirmer, et al.; PNAS 103, 4234 (2006) Abstract; Full Text
Chemistry and biology of resorcylic acid lactones: N. Winssinger, et al.; Chem. Commun. (Camb). 1, 22 (2007), (Review) Abstract
Further Categories Containing This Product:
MAPK Pathway Inhibitors • Antibiotics - Protein Kinase Inhibitors • CDKs & Cyclins Other Products • Tyrosine Kinase Inhibitors • Antitumor Agents (DNA Interaction & Gene Regulation) • Antitumor Antibiotics • Antibiotics - Proteasome/Ubiquitin Modulators • Ubiquitination Other Products • Ras Signalling Pathway Other Products
 
 
ALX-159-600 Revised 14-Jul-08
JNK Inhibitor 1 (L-stereoisomer)
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SYNONYMS L-JNKI1
c-Jun N-terminal Kinase Peptide Inhibitor 1, L-stereoisomer
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY JNK [SAPK1]/Related Products
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ALX-159-600-R100   100 µl 125.00 USD Add To Cart
ALX-159-600-R200   200 µl 225.00 USD Add To Cart
Product Specification
SEQUENCE: GRKKRRQRRR-PP-RPKRPTTLNLFPQVPRSQD-amide
FORMULA: C164H286N66O40
MW: 3822.5
CONCENTRATION: 1mM
PURITY: ≥97% (HPLC)
FORMULATION: Liquid. Sterile, ready-to-use solution in PBS.
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
HANDLING: After opening, prepare aliquots and store at -20°C. Avoid freeze/thaw cycles. Keep on ice at all times.
POSITIVE CONTROL: Prod. No. ALX-168-009/1
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Product Description

Cell permeable JNK (c-Jun N-terminal kinase) inhibitor. For increased cell permeability the peptide was covalently linked to the 10 aa recognized by the TAT transporter. Neuroprotective agent for stroke.
Product Specific Literature References
[1] Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death: C. Bonny, et al.; Diabetes 50, 77 (2001) Abstract; Full Text
Hyperosmolarity and CD95L trigger CD95/EGF receptor association and tyrosine phosphorylation of CD95 as prerequisites for CD95 membrane trafficking and DISC formation: R. Reinehr, et al.; FASEB J. 17, 731 (2003) Abstract
Translation inhibitors sensitize prostate cancer cells to TRAIL-induced apoptosis by activating c-Jun N-terminal kinase: N.K. Sah, et al.; J. Biol. Chem. 278, 20593 (2003) Abstract; Full Text
A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia: T. Borsello, et al.; Nat. Med. 9, 1180 (2003) Abstract
Activation of JNK in sensory neurons protects against sensory neuron cell death in diabetes and on exposure to glucose/oxidative stress in vitro: S.A. Price, et al.; Ann. NY Acad. Sci. 1010, 95 (2003)
Insulin-secreting beta-cell dysfunction induced by human lipoproteins: M.E. Roehrich, et al.; J. Biol. Chem. 278, 18368 (2003) Abstract; Full Text
Inhibition of c-Jun NH2-terminal kinase activity improves ischemia/reperfusion injury in rat lungs: M. Ishii, et al.; J. Immunol. 172, 2569 (2004) Abstract
General Information
BACKGROUND/TECHNICAL INFORMATION A protein inhibitor named IB1 has been described that competitively blocks the interaction between JNK and c-Jun, thereby inhibiting the signalling events downstream of JNK [2,3] like c-Jun, ATF2 and ELK1 phosphorylation. To convert IB1 into cell-permeable inhibitors of JNK (JNKI peptides) the minimal 20 aa inhibitory sequence of IB1 was covalently linked to the 10 amino acids recognized by TAT transporter [4].
The L-JNKI1 and the protease resistant D-JNKI1 peptides represent the only potent inhibitors that are specific for JNK (JNK1, JNK2 and JNK3). Different from chemical inhibitors that directly affect kinase activity e.g. by competing with the ATP-binding site of the protein kinase, JNKI1 rather inhibits the interaction between JNK and its substrate, resulting in a JNK K.O. phenotype. In contrast to pure diffusion the TAT-peptides are actively transported into cells, where they remain until their proteolytic degradation. They can be used for in vitro as well as for in vivo applications (IC50~1µM).
D-JNKI1 is the only form found to be active on neuronal cells, probably due to a high level of proteolytic degradation of the L-stereoisomer (T. Borsello and C. Bonny; unpublished data). As these peptides tend to be toxic in neurons above concentrations of 5µM, it is recommended to use concentrations of ~1µM or less. When interpreting results of c-Jun inhibition, one should also note that a number of other c-Jun kinases are thought to contribute to c-Jun phosphorylation (C. Bonny, personal communication).

*For in vivo applications in mice it is suggested to start with 30-50µl of a 1mM stock solution administered intraperitoneally. Cellular uptake of L-JNKI1 peptides can now be confirmed using the FITC-conjugated L-TAT control peptide (Prod. No. ALX-168-009F).
Note: L-TAT control peptides should only be used with L-JNKI1.
General Literature References
[2] IB1, a JIP-1-related nuclear protein present in insulin-secreting cells: C. Bonny, et al.; J. Biol. Chem. 273, 1843 (1998) Abstract; Full Text
[3] A cytoplasmic inhibitor of the JNK signal transduction pathway: M. Dickens, et al.; Science 277, 693 (1997) Abstract
[4] In vivo protein transduction: delivery of a biologically active protein into the mouse: S.R. Schwarze, et al.; Science 285, 1569 (1999) Abstract
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Further Categories Containing This Product:
MAPK Pathway Inhibitors • Peptides
 
 
ALX-380-267 Revised 11-Feb-08
LL-Z1640-2
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PRODUCT LINE Natural Products / Antibiotics
PRODUCT CATEGORY Antibiotics - Protein Kinase Inhibitors
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ALX-380-267-M001   1 mg 50.00 USD Add To Cart
ALX-380-267-M005   5 mg 200.00 USD Add To Cart
Product Specification
FORMULA: C19H22O7
MW: 362.4
CAS NUMBER: 66018-38-0
SOURCE/HOST: Isolated from Deuteromycetes sp.
PURITY: ≥95% (HPLC)
APPEARANCE: White to off-white solid.
SOLUBILITY: Soluble in methanol, chloroform or ethil acetate.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C

Product Description
Inhibitor of the JNK/p38 pathways. Inhibits anisomycin-induced but not TNF-induced JNK/p38 activation. Potent protein kinase inhibitor.
Product Specific Literature References
A radicicol-related macrocyclic nonaketide compound, antibiotic LL-Z1640-2, inhibits the JNK/p38 pathways in signal-specific manner: K. Takehana, et al.; BBRC 257, 19 (1999) Abstract
Inhibition of HgCl2-induced mitogen-activated protein kinase activation by LL-Z1640-2 in CCRF-CEM cells: M. Matsuoka, et al.; Eur. J. Pharmacol. 409, 155 (2000) Abstract
Cadmium induces phosphorylation of p53 at serine 15 in MCF-7 cells: M. Matsuoka & H. Igisu; BBRC 282, 1120 (2001) Abstract
Effects of pentachlorophenol and tetrachlorohydroquinone on mitogen-activated protein kinase pathways in Jurkat T cells: B. Wispriyono, et al.; Environ. Health Perspect. 110, 139 (2002) Abstract; Full Text
Pharmacological inhibitors of MAPK pathways: J.M. English & M.H. Cobb; TIPS 23, 40 (2002), (Review) Abstract
Suppression of cadmium-induced JNK/p38 activation and HSP70 family gene expression by LL-Z1640-2 in NIH3T3 cells: N. Sugisawa, et al.; Toxicol. Appl. Pharmacol. 196, 206 (2004) Abstract
JNK (c-Jun NH2 terminal kinase) and p38 during ischemia reperfusion injury in the small intestine: T. Murayama, et al.; Transplantation 81, 1325 (2006) Abstract
Involvement of the extracellular signal-regulated protein kinase pathway in phosphorylation of p53 protein and exerting cytotoxicity in human neuroblastoma cells (SH-SY5Y) exposed to acrylamide: T. Okuno, et al.; Arch. Toxicol. 80, 146 (2006) Abstract
Protein kinases as small molecule inhibitor targets in inflammation: M. Gaestel, et al.; Curr. Med. Chem. 14, 2214 (2007), (Review) Abstract
Chemistry and biology of resorcylic acid lactones: N. Winssinger & S. Barluenga; Chem. Commun. 1, 22 (2007), (Review) Abstract; Full Text
Further Categories Containing This Product:
JNK [SAPK1]/Related Products
 
 
ALX-430-142 Revised 30-Nov-06
Locostatin
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SYNONYMS UIC-1005
(4S)-3-[(E)-But-2-enoyl]-4-benzyl-2-oxazolidinone
(4S)-3-[(E)-1-Oxo-2-butenyl]-4-(phenylmethyl)-2-oxazolidinone
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY MAPK Pathway Inhibitors
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ALX-430-142-M005   5 mg 80.00 USD Add To Cart
Product Specification
FORMULA: C14H15NO3
MW: 245.3
PURITY: ≥95%
APPEARANCE: White solid.
SOLUBILITY: Soluble in DMSO (10mg/ml) or methanol (50mg/ml).
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
HANDLING: Protect from light.
HAZARD: HARMFUL. MAY BE MUTAGENIC.
IDENTITY: Identity determined by 1H-NMR and MS.

Product Description
Cell permeable, potent inhibitor of interaction of Raf kinase inhibitor protein (RKIP) with Raf1 kinase. Blocks eukaryotic cell migration (IC50=14µM for inhibition of wound closure in MDCK cell monolayers). Inhibitor of early development in frog embryos and tissue dynamics in embryonic explants. Displays no antibacterial activity.
Product Specific Literature References
A non-antibacterial oxazolidinone derivative that inhibits epithelial cell sheet migration: K.T. Mc Henry, et al.; ChemBioChem 3, 1105 (2002) Abstract
A chemical inhibitor reveals the role of Raf kinase inhibitor protein in cell migration: S. Zhu, et al.; Chem. Biol. 12, 981 (2005) Abstract
A role for RKIP in cell motility: W.M. Bement; Chem. Biol. 12, 953 (2005) Abstract
Sustained activation of Src-family tyrosine kinases by ischemia: A potential mechanism mediating extracellular signal-regulated kinase cascades in hippocampal dentate gyrus: J. Guo, et al.; Neuroscience 143, 827 (2006) Abstract
 
 
ALX-168-009F Revised 28-Jul-08 New product
L-TAT Control Peptide (for Prod. No. ALX-159-600) (FITC)
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SYNONYMS JNK Inhibitor 1 (L-stereoisomer) Control Peptide (for Prod. No. ALX-159-600) (FITC)
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY JNK [SAPK1]/Related Products
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ALX-168-009F-R050 FITC 50 µl 110.00 USD Add To Cart
Product Specification
SEQUENCE: FITC-β-A-RKKRRQRRRA-amide
FORMULA: C80H128N34O17S
MW: 1870.2
CONCENTRATION: 1mM
PURITY: ≥90% (HPLC)
FORMULATION: Liquid. In sterile PBS.
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
HANDLING: Avoid freeze/thaw cycles. After opening, prepare aliquots and store at -20°C. Keep on ice at all times.
Product Description
Control peptide for L-JNKI. For more details see L-JNKI1 (Prod.No. ALX-159-600).
Product Specific Literature References
Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death: C. Bonny, et al.; Diabetes 50, 77 (2001) Abstract; Full Text
Hyperosmolarity and CD95L trigger CD95/EGF receptor association and tyrosine phosphorylation of CD95 as prerequisites for CD95 membrane trafficking and DISC formation: R. Reinehr, et al.; FASEB J. 17, 731 (2003) Abstract; Full Text
Related Products
Further Categories Containing This Product:
Peptides
 
 
ALX-804-061 Revised 24-Jun-08
Monoclonal Antibody to ERK1/2 (phosphorylated) (12D4)
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SYNONYMS anti-MAPK2/3 (phosphorylated) MAb (12D4)
anti-MAP Kinase 2/3 (phosphorylated) MAb (12D4)
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY ERK1 & ERK2/Related Products
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ALX-804-061-C100   100 µg 453.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
Mouse
Rat
Dog
CLONE: 12D4
ISOTYPE: Mouse IgG1
PURITY DETAIL: Purified from serum-free cell culture supernatant by subsequent thiophilic adsorption and size exclusion chromatography.
FORMULATION: Lyophilized from 1ml 2x PBS, 0.09% sodium azide, PEG and sucrose.
RECONSTITUTION: Reconstitute with 1ml distilled water (15 min., RT).
IMMUNOGEN: Peptide comprising the pThr-Glu-pTyr motif in activated ERK1 and ERK2.
SPECIFICITY: Recognizes the pThr-Glu-pTyr motif of activated human, mouse, rat and dog ERK1 and ERK2. Requires phosphorylation both at the threonine and the tyrosine site and does not cross-react with the non-phosphorylated form of the protein. Does not cross-react with activated JNK or p38.
APPLICATION: Immunocytochemistry (1-10µg/ml)
Immunohistochemistry
Immunoprecipitation (1-10µg per 106 pervanadate-treated A431 or HepG2 cells)
Western Blot (0.5µg/ml for HRPO/ECL detection).
Recommended blocking buffer CPPT: 10mM TRIS-HCl, pH 7.4, 0.5% (w/v) casein, 1% (w/v) PEG 4’000, 1% (w/v) polyvinylpyrrolidone, 0.1% (v/v) Tween 20, 150mM sodium chloride.
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
USE/STABILITY: Reconstituted antibody is stable for 1 year when stored at -80°C. Thaw aliquots at +37°C. Thawed aliquots may be stored at +4°C for up to 3 months.
HANDLING: After reconstitution, prepare aliquots and freeze in liquid nitrogen. Avoid freeze/thaw cycles.
POSITIVE CONTROL: Included (Prod. No. ALX-840-025).
Product Specific Literature References
IL-4-induced priming of human intestinal mast cells for enhanced survival and Th2 cytokine generation is reversible and associated with increased activity of ERK1/2 and c-Fos: A. Lorentz, et al.; J. Immunol. 174, 6751 (2005) Abstract; Full Text
Further Categories Containing This Product:
Phospho-specific Antibodies • Monoclonal Antibodies
 
 
ALX-804-288 Revised 20-Sep-07
Monoclonal Antibody to ERK2 (6G11)
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SYNONYMS anti-MAPK2 MAb (6G11)
anti-MAP Kinase 2 MAb (6G11)
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY ERK1 & ERK2/Related Products
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ALX-804-288-C100   100 µg 380.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
Mouse
Rat
Dog
CLONE: 6G11
ISOTYPE: Mouse IgG1
PURITY DETAIL: Purified from serum-free cell culture supernatant by subsequent thiophilic adsorption and size exclusion chromatography.
FORMULATION: Lyophilized from 1ml 2x PBS, 0.09% sodium azide, PEG and sucrose.
RECONSTITUTION: Reconstitute with 1ml distilled water (15 min., RT).
IMMUNOGEN: Synthetic peptide comprising the pThr-Glu-pTyr motif in activated ERK1 and ERK2.
SPECIFICITY: Recognizes the C-terminus of human, mouse, rat and dog ERK2. Does not cross-react with ERK1.
APPLICATION: Immunoprecipitation
Western Blot (0.5µg/ml for HRPO/ECL detection).
Recommended blocking buffer milk: 2x PBS, 5-8% (w/v) dry milk powder and 0.1% (v/v) Tween 20.
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
USE/STABILITY: Reconstituted antibody is stable for 1 year when stored at -80°C. Thaw aliquots at +37°C. Thawed aliquots may be stored at +4°C for up to 3 months.
HANDLING: Avoid freeze/thaw cycles. After reconstitution, prepare aliquots and freeze in liquid nitrogen.
POSITIVE CONTROL INCLUDED: yes
Product Specific Literature References
IL-4-induced priming of human intestinal mast cells for enhanced survival and Th2 cytokine generation is reversible and associated with increased activity of ERK1/2 and c-Fos: A. Lorentz, et al.; J. Immunol. 174, 6751 (2005) Abstract; Full Text
Further Categories Containing This Product:
Monoclonal Antibodies
 
 
ALX-804-241 Revised 30-May-08
Monoclonal Antibody to JNK/p38 (phosphorylated) (9H8)
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SYNONYMS anti-SAPK1/2 (phosphorylated) MAb (9H8)
anti-SAP Kinase 1/2 (phosphorylated) MAb (9H8)
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY JNK [SAPK1]/Related Products
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ALX-804-241-C100   100 µg 453.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
Mouse
CLONE: 9H8
ISOTYPE: Mouse IgG1
PURITY DETAIL: Purified from serum-free cell culture supernatant by subsequent thiophilic adsorption and size exclusion chromatography.
FORMULATION: Lyophilized from 1ml 2x PBS, 0.09% sodium azide, PEG and sucrose.
RECONSTITUTION: Reconstitute with 1ml distilled water (15 min., RT).
IMMUNOGEN: Synthetic peptide corresponding to a portion of phosphorylated JNK and p38.
SPECIFICITY: Recognizes the TG/PpT motif of activated, monophosphorylated and the dually phosphorylated site pTG/PpT of human and mouse JNK and p38. Does not cross-react with the non-phosphorylated form of the protein or with activated ERK1 or ERK2.
APPLICATION: Immunohistochemistry
Immunoprecipitation
Western Blot: Recommended blocking buffer CPPT: 10mM TRIS-HCl, pH 7.4, 0.5% (w/v) casein, 1% (w/v) PEG 4’000, 1% (w/v) polyvinylpyrrolidone, 0.1% (v/v) Tween 20, 150mM sodium chloride.
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
USE/STABILITY: Reconstituted antibody is stable for 1 year when stored at -80°C. Thaw aliquots at +37°C. Thawed aliquots may be stored at +4°C for up to 3 months.
HANDLING: Avoid freeze/thaw cycles. After reconstitution, prepare aliquots and freeze in liquid nitrogen.
POSITIVE CONTROL: Included (Prod. No. ALX-840-037).
Product Description
Stress-activated Protein Kinases (SAPKs) are strongly activated in response to adverse stimuli such as heat and osmotic shock, UV light and other DNA-damaging reagents, and inhibitors of protein synthesis. They are also activated strongly in response to agonists that are released or produced under conditions of stress, such as proinflammatory cytokines
Further Categories Containing This Product:
Phospho-specific Antibodies • p38 Kinases/Related Products • Monoclonal Antibodies
 
 
ALX-804-394 Revised 05-Jun-07
Monoclonal Antibody to Mxi2 (2F2)
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PRODUCT LINE Signal Transduction
PRODUCT CATEGORY p38 Kinases/Related Products
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ALX-804-394-C100   100 µg 380.00 USD Add To Cart
Product Specification
SPECIES CROSSREACTIVITY:
Human
Mouse
Rat
Dog
CLONE: 2F2
ISOTYPE: Mouse IgG1
PURITY DETAIL: Purified from serum-free cell culture supernatant by subsequent thiophilic adsorption and size exclusion chromatography.
FORMULATION: Lyophilized from 1ml 2x PBS, 0.09% sodium azide, PEG and sucrose.
RECONSTITUTION: Reconstitute with 1ml distilled water (15 min., RT).
IMMUNOGEN: Synthetic peptide corresponding to N-terminal human p38.
SPECIFICITY: Recognizes the N-terminus of human, mouse, rat and dog p38 splice variant Mxi2. Does not cross-react with p38 (SAPK2a).