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MAP Kinase Pathways
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ALX-270-022 Revised 09-Jan-08
AEBSF . hydrochloride
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SYNONYMS 4-(2-Aminoethyl)benzenesulfonylfluoride . HCl
Pefabloc®SC
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY Proteases Other Products
Ordering Information
Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-270-022-M050   50 mg 40.00 USD Add To Cart
ALX-270-022-M250   250 mg 145.00 USD Add To Cart
ALX-270-022-G001   1 g 360.00 USD Add To Cart
Product Specification
FORMULA: C8H10FNO2S . HCl
MW: 203.2 . 36.5
CAS NUMBER: 30827-99-7
PURITY: ≥98% (HPLC)
APPEARANCE: White to off-white powder.
SOLUBILITY: Soluble in water or 100% ethanol.
SHIPPING: AMBIENT
LONG TERM STORAGE: +4°C
HANDLING: Protect from moisture.

Product Description
Specific irreversible inhibitor of serine proteases including trypsin, chymotrypsin, plasmin, plasma kallikrein, and thrombin. Stable, non-toxic alternative to PMSF (Prod. No. ALX-270-184). Inhibitor of NAD(P)H oxidase. Activator of MAP kinases JNK and p38.
Product Specific Literature References
Irreversible enzyme inhibitors. 180. Irreversible inhibitors of the C'la component of complement derived from m-(phenoxypropoxy)benzamidine and phenoxyacetamide: B.R. Baker & H.J. Cory; J. Med. Chem. 14, 119 (1971) Abstract
Serine protease inhibitors block priming of monocytes for enhanced release of superoxide: P. Megyeri, et al.; Immunology 86, 629 (1995) Abstract; Full Text
Inhibition of amyloid beta-protein production in neural cells by the serine protease inhibitor AEBSF: M. Citron, et al.; Neuron 17, 171 (1996) Abstract
Lysis of leukemic cells by human macrophages: inhibition by 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor: Y. Nakabo & M.J. Pabst; J. Leukoc. Biol. 60, 328 (1996) Abstract; Full Text
Inhibition of NADPH oxidase activation by 4-(2-aminoethyl)-benzenesulfonyl fluoride and related compounds: V. Diatchuk, et al.; J. Biol. Chem. 272, 13292 (1997) Abstract; Full Text
4-(2-Aminoethyl)benzenesulfonyl fluoride attenuates tumor-necrosis-factor-alpha-induced blood-brain barrier opening: P. Megyeri, et al.; Eur. J. Pharmacol. 374, 207 (1999) Abstract
Evaluation of two inhibitors of invasion: LY311727 [3-(3-acetamide-1-benzyl-2-ethyl-indolyl-5-oxy)propane phosphonic acid] and AEBSF [4-(2-aminoethyl)-benzenesulphonyl fluoride] in acute murine toxoplasmosis: R. Buitrago-Rey, et al.; J. Antimicrob. Chemother. 49, 871 (2002) Abstract; Full Text
Heme oxygenase-1 gene activation by the NAD(P)H oxidase inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride via a protein kinase B, p38-dependent signaling pathway in monocytes: N. Wijayanti, et al.; J. Biol. Chem. 280, 21820 (2005) Abstract; Full Text
Inhibitory effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride, a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression: T. Hosoi, et al.; Eur. J. Pharmacol. 554, 8 (2007) Abstract
Further Categories Containing This Product:
Heme Oxygenase / Related Products • MAPK Pathway Activators • Cell Stress, Oxidative Stress & Redox Signalling Other Products • Fatty Acid Amide Hydrolase [FAAH] / Related Products
 
 
ALX-270-448 Revised 24-Jul-06
ALK5 Inhibitor I
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SYNONYMS TGF-β RI Kinase Inhibitor I
3-(Pyridin-2-yl)-4-(4-quinonyl)]-1H-pyrazole
PRODUCT LINE Chemokines & Cytokines
PRODUCT CATEGORY Transforming Growth Factor beta [TGFbeta] & Receptors / Related Products
Ordering Information
Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-270-448-M001   1 mg 30.00 USD Add To Cart
ALX-270-448-M005   5 mg 90.00 USD Add To Cart
Product Specification
FORMULA: C17H12N4
MW: 272.3
PURITY: ≥97% (1H-NMR)
APPEARANCE: Yellow to brown solid.
SOLUBILITY: Soluble in DMSO or methanol.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
USE/STABILITY: Stable for 2 years after receipt when stored at -20°C. Stock solutions are stable for up to 3 months when stored at -20°C.
HANDLING: Protect from light.
HAZARD: MAY BE CARCINOGENIC. HARMFUL.

Product Description

Cell permeable, potent, selective and ATP-competitive inhibitor of TGF-β RI kinase (IC50=51nM). Displays ~15-fold greater selectivity over p38α MAPK (IC50=740nM). Inhibits TGF-β-dependent cellular growth (IC50=89nM in NIH 3T3 mouse fibroblasts) and transcription activation (IC50=47nM in mink lung cells).
Product Specific Literature References
Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain: J.S. Sawyer, et al.; J. Med. Chem. 46, 3953 (2003) Abstract
Successful shape-based virtual screening: the discovery of a potent inhibitor of the type I TGFbeta receptor kinase (TbetaRI): J. Singh, et al.; Bioorg. Med. Chem. Lett. 13, 4355 (2003) Abstract
Further Categories Containing This Product:
MAPK Pathway Inhibitors
 
 
ALX-270-445 Revised 20-Jul-06
ALK5 Inhibitor II
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SYNONYMS TGF-β RI Kinase Inhibitor II
2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine
PRODUCT LINE Chemokines & Cytokines
PRODUCT CATEGORY Transforming Growth Factor beta [TGFbeta] & Receptors / Related Products
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Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-270-445-M001   1 mg 60.00 USD Add To Cart
ALX-270-445-M005   5 mg 240.00 USD Add To Cart
Product Specification
FORMULA: C17H13N5
MW: 287.3
PURITY: ≥97% (1H-NMR)
APPEARANCE: Yellow solid.
SOLUBILITY: 5mg/ml soluble in DMSO or methanol.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
USE/STABILITY: Stable for 2 years after receipt when stored at -20°C. Stock solutions are stable for up to 6 months when stored at -20°C.
HANDLING: Protect from light.

Product Description
Cell permeable, potent, selective and ATP-competitive inhibitor of TGF-β RI kinase (IC50=23nM, 4nM and 18nM for binding, auto-phosphorylation and cellular assay in HepG2 cells of TGF-β RI kinase, respectively). Minimally affects a panel of 9 closely related kinases including p38 MAPK (IC50>16µM).
Product Specific Literature References
Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors: F. Gellibert, et al.; J. Med. Chem. 47, 4494 (2004) Abstract
Further Categories Containing This Product:
MAPK Pathway Inhibitors
 
 
ALX-270-385 Revised 17-Jul-07
Aloisine A
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SYNONYMS RP107
7-n-Butyl-6-(4-hydroxyphenyl)[5H]pyrrolo[2,3-b]pyrazine
PRODUCT LINE Cell Cycle
PRODUCT CATEGORY CDK & Cyclin Inhibitors
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ALX-270-385-M001   1 mg 30.00 USD Add To Cart
Product Specification
FORMULA: C16H17N3O
MW: 267.3
PURITY: ≥95%
APPEARANCE: Yellow solid.
SOLUBILITY: Soluble in DMSO.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
HANDLING: Protect from light. Packaged under inert gas.

Product Description
Cell permeable, potent, selective, reversible and ATP-competitive inhibitor of CDK1/cyclin B (IC50=150nM), CDK2/cyclin A (IC50=120nM), CDK2/cyclin E (IC50=400nM), CDK5/p25
(IC50=200nM), CDK5/p35 (IC50=160nM) and GSK-3α (IC50=500nM). Also inhibits GSK-3β (IC50=650nM) and c-Jun N-terminal kinase (JNK) (IC50~3-10µM). Poor inhibitor of CK1, CK2, CDK4/cyclin D1, MAPKK, PKA, PKG, PKCs and c-raf (IC50≥100µM). Blocks cell cycle in both G1 and G2 phase.
Product Specific Literature References
Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects: Y. Mettey, et al.; J. Med. Chem. 46, 222 (2003) Abstract
Further Categories Containing This Product:
GSK-3 Inhibitors • JNK [SAPK1] / Related Products • Cell Cycle Blockers & Inhibitors / Related Products
 
 
ALX-340-029 Revised 08-Jul-08
Anandamide
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SYNONYMS AEA
N-Arachidonoylethanolamine
(all-Z)-N-(2-Hydroxyethyl)-5,8,11,14-eicosatetraenamide
PRODUCT LINE Neurobiology
PRODUCT CATEGORY Anandamide & Anandamide Analogs
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ALX-340-029-M005   5 mg 51.00 USD Add To Cart
Product Specification
FORMULA: C22H37NO2
MW: 347.5
CAS NUMBER: 94421-68-8
MERCK INDEX: 14: 624
RTECS: JX3842500
CONCENTRATION: 50mg/ml 
PURITY: ≥98%
FORMULATION: Liquid. Solution in ethanol.
SOLUBILITY: 10mg/ml soluble in DMSO or dimethyl formamide.
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
USE/STABILITY: Stable for at least 1 year after receipt when stored at -20°C. Stable for at least 6 months in other organic solvents when stored at -20°C.
HANDLING: Protect from light and oxygen.

Product Description
Endogenous [1] ligand for the CB1 receptor (CB1: Ki=52nm; CB2: Ki=1930nm [2]) and TRPV1 (Ki=5.78µM [3,4]). Inhibits NF-κB activation through direct binding to IKKβ [5] and induces apoptosis independently of cannabinoid or vanilloid receptors [6]. Activates the MAP kinase (MAPK/ERK) signalling pathway [7].
Product Specific Literature References
[1] Isolation and structure of a brain constituent that binds to the cannabinoid receptor: W.A. Devane, et al.; Science 258, 1946 (1992) Abstract
[2] Novel analogues of arachidonylethanolamide (anandamide): affinities for the CB1 and CB2 cannabinoid receptors and metabolic stability: S. Lin, et al.; J. Med. Chem. 41, 5353 (1998) Abstract
[3] Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide: P.M. Zygmunt, et al.; Nature 400, 452 (1999) Abstract
[4] Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens: R.A. Ross, et al.; Br. J. Pharmacol. 132, 631 (2001) Abstract
[5] Anandamide inhibits nuclear factor-kappaB activation through a cannabinoid receptor-independent pathway: R. Sancho, et al.; Mol. Pharmacol. 63, 429 (2003) Abstract
[6] Anandamide induces cell death independently of cannabinoid receptors or vanilloid receptor 1: possible involvement of lipid rafts: K.P. Sarker, et al.; Cell Mol. Life Sci. 60, 1200 (2003) Abstract
[7] The MAP kinase signal transduction pathway is activated by the endogenous cannabinoid anandamide: M. Wartmann, et al.; FEBS Lett. 359, 133 (1995) Abstract
Biochemistry and pharmacology of arachidonylethanolamide, a putative endogenous cannabinoid: C.J. Hillard & W.B. Campbell; J. Lipid Res. 38, 2383 (1997), (Review) Abstract
The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation: L. De Petrocellis, et al.; PNAS 95, 8375 (1998) Abstract
Cannabinoid receptors and their endogenous agonist, anandamide: J. Axelrod & C.C. Felder; Neurochem. Res. 23, 575 (1998), (Review) Abstract
Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action: V. Di Marzo, et al.; TINS 21, 521 (1998), (Review) Abstract
Endocannabinoids: a new class of vasoactive substances: M.D. Randall & D.A. Kendall; TIPS 19, 55 (1998), (Review) Abstract
Metabolism of anandamide and 2-arachidonoylglycerol: an historical overview and some recent developments: V. Di Marzo, et al.; Lipids 34, S319 (1999), (Review) Abstract
Anandamide: a candidate neurotransmitter heads for the big leagues: D.W. Self; Nat. Neurosci. 2, 303 (1999), (Review) Abstract
New perspectives on enigmatic vanilloid receptors: A. Szallasi & V. Di Marzo; TINS 23, 491 (2000), (Review) Abstract
Anandamide: some like it hot: V. Di Marzo, et al.; TIPS 22, 346 (2001), (Review) Abstract
Anandamide is an endogenous inhibitor for the migration of tumor cells and T lymphocytes: J. Joseph, et al.; Cancer Immunol. Immunother. 53, 723 (2004) Abstract
Anandamide-induced cell death in primary neuronal cultures: role of calpain and caspase pathways: V.A. Movsesyan, et al.; Cell Death Differ. 11, 1121 (2004) Abstract
Arachidonylethanolamide induces apoptosis of human glioma cells through vanilloid receptor-1: E. Contassot, et al.; J. Neuropathol. Exp. Neurol. 63, 956 (2004) Abstract
Preferred conformations of endogenous cannabinoid ligand anandamide: J.Z. Chen, et al.; Life Sci. 76, 2053 (2005) Abstract
The cardiovascular actions of anandamide: more targets?: M.D. Randall; Br. J. Pharmacol. 145, 565 (2005) Abstract; Full Text
Accumulation of anandamide: Evidence for cellular diversity: C.J. Hillard and A. Jarrahian; Neuropharmacology 48, 1072 (2005) Abstract
Anandamide as an intracellular messenger regulating ion channel activity: M. van der Stelt and V. Di Marzo; Prostaglandins Other Lipid Mediat. 77, 111 (2005) Abstract
Anandamide reduces infarct size in rat isolated hearts subjected to ischaemia-reperfusion by a novel cannabinoid mechanism: N.J. Underdown, et al.; Br. J. Pharmacol. 146, 809 (2005) Abstract
Anandamide inhibits adhesion and migration of breast cancer cells: C. Grimaldi, et al.; Exp. Cell Res. 312, 363 (2006) Abstract
General Information
BACKGROUND/TECHNICAL INFORMATION To change the solvent, evaporate the ethanol under a gentle stream of nitrogen and immediately add the solvent of choice.
Further Categories Containing This Product:
Endocannabinoids • MAPK Pathway Activators • Apoptosis Inducers & Inhibitors Other Products • Endovanilloids • NF-kB Pathway Inhibitors
 
 
ALX-380-051 Revised 20-Jun-08
Anisomycin
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SYNONYMS 2-(p-Methoxybenzyl)-3,4-pyrrolidinediol-3-acetate
PRODUCT LINE Natural Products / Antibiotics
PRODUCT CATEGORY Antibiotics - Other Signal Transduction Pathway Modulators
Ordering Information
Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-380-051-M010   10 mg 35.00 USD Add To Cart
ALX-380-051-M050   50 mg 140.00 USD Add To Cart
ALX-380-051-M100   100 mg 250.00 USD Add To Cart
Product Specification
FORMULA: C14H19NO4
MW: 265.3
CAS NUMBER: 22862-76-6
MERCK INDEX: 14: 670
RTECS: BZ9800000
SOURCE/HOST: Isolated from Streptomyces griseolus.
PURITY: ≥98% (HPLC)
APPEARANCE: White crystalline solid.
SOLUBILITY: Soluble in DMSO (25mg/ml), 100% ethanol, methanol or ethyl acetate (10mg/ml).
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
HAZARD: TOXIC.

Product Description
Antibiotic. Activator of p38 and MAP kinases. Synergistic with growth factors and phorbol esters to superinduce cFos and cJun, by acting as a potent signalling agonist. Induces apoptosis in the human monoblastoid cell line. Used in the eradication of bean mildew. Inhibits other pathogenic fungi in plants.
Product Specific Literature References
Anisomycin, a new anti-protozoan antibiotic: B. A. Sobin & F. W. Tanner; J. Am. Chem. Soc. 76, 4053 (1954)
DNA fragmentation and cytolysis in U937 cells treated with diphtheria toxin or other inhibitors of protein synthesis: S.K. Kochi & R.J. Collier; Exp. Cell. Res. 208, 296 (1993) Abstract
The stress-activated protein kinase subfamily of c-Jun kinases: J.M. Kyriakis, et al.; Nature 369, 156 (1994) Abstract
Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun: I. Sanchez, et al.; Nature 372, 794 (1994) Abstract
Anisomycin and rapamycin define an area upstream of p70/85S6k containing a bifurcation to histone H3-HMG-like protein phosphorylation and c-fos-c-jun induction: E. Kardalinou, et al.; Mol. Cell. Biol. 14, 1066 (1994) Abstract
Protein synthesis inhibitor phase shifts vasopressin rhythms in long- term suprachiasmatic cultures: K. Shinohara & T. Oka; NeuroReport 5, 2201 (1994) Abstract
Anisomycin selectively desensitizes signalling components involved in stress kinase activation and fos and jun induction: C.A. Hazzalin, et al.; Mol Cell Biol 18, 1844 (1998) Abstract
Anisomycin treatment paradigm affects duration of long-term potentiation in slices of the amygdala: P. Okulski, et al.; Neuroscience 114, 1 (2002) Abstract
Downregulation of Ski and SnoN co-repressors by anisomycin: A. Vazquez-Macias, et al.; FEBS Lett. 579, 3701 (2005) Abstract
Anisomycin and the reconsolidation hypothesis: J.W. Rudy, et al.; Learn. Mem. 13, 1 (2006), Review Abstract
A chemical screen identifies anisomycin as an anoikis sensitizer that functions by decreasing FLIP protein synthesis: I.A. Mawji, et al.; Cancer Res. 67, 8307 (2007) Abstract
Anisomycin abrogates repression of protooncogene c-fos transcription in E1A + cHa-ras-transformed cells through activation of MEK/ERK kinase cascade: A. N. Kukushkin, et al.; J. Cell. Biochem. 103, 1005 (2008) Abstract
Further Categories Containing This Product:
MAPK Pathway Activators • Antibiotics - Apoptosis Inducers & Inhibitors • JNK [SAPK1] / Related Products
 
 
ALX-385-008 Revised 13-Mar-08
Apigenin
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SYNONYMS 4',5,7-Trihydroxyflavone
PRODUCT LINE Natural Products / Antibiotics
PRODUCT CATEGORY Flavones
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Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-385-008-M010   10 mg 35.00 USD Add To Cart
ALX-385-008-M050   50 mg 105.00 USD Add To Cart
Product Specification
FORMULA: C15H10O5
MW: 270.2
CAS NUMBER: 520-36-5
MERCK INDEX: 14: 730
SOURCE/HOST: Synthetic.
PURITY: ≥90% (HPLC)
APPEARANCE: Light yellow to slightly brown powder.
SOLUBILITY: Soluble in diluted potassium hydroxide or DMSO; slightly soluble in 100% ethanol (hot). Insoluble in water.
SHIPPING: AMBIENT
LONG TERM STORAGE: +4°C
HAZARD: IRRITANT.

Product Description
Antioxidant flavonoid. Has chemopreventive and antitumor properties. Induces apoptosis. Inhibits the proliferation of malignant tumor cells by G2/M arrest. MAP kinase (MAPK/ERK) inhibitor. Inhibits hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) expression.
Product Specific Literature References
Apigenin and tangeretin enhance gap junctional intercellular communication in rat liver epithelial cells: C. Chaumontet, et al.; Carcinogenesis 15, 2325 (1994) Abstract
Apigenin induces morphological differentiation and G2-M arrest in rat neuronal cells: F. Sato, et al.; BBRC 204, 578 (1994) Abstract
Reversion of v-H-ras-transformed NIH 3T3 cells by apigenin through inhibiting mitogen activated protein kinase and its downstream oncogenes: M.L. Kuo and N.C. Yang; BBRC 212, 767 (1995) Abstract
Structure-antioxidant activity relationships of flavonoids and phenolic acids: C.A. Rice-Evans, et al.; Free Radical Biol. & Med. 20, 933 (1996), (Review) Abstract
Apigenin inhibits endothelial-cell proliferation in G(2)/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression: V. Trochon, et al.; Int. J. Cancer 85, 691 (2000) Abstract
Induction of caspase-dependent, p53-mediated apoptosis by apigenin in human neuroblastoma: R. Torkin, et al.; Mol. Cancer Ther. 4, 1 (2005) Abstract
Apigenin and cancer chemoprevention: progress, potential and promise: D. Patel, et al.; Int. J. Oncol. 30, 233 (2007), (Review) Abstract
Apigenin inhibits tumor angiogenesis through decreasing HIF-1alpha and VEGF expression: J. Fang, et al.; Carcinogenesis 28, 858 (2007) Abstract
Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells: S. Shukla & S. Gupta; Cell Cycle 6, 1102 (2007) Abstract
Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-kappaB through the suppression of p65 phosphorylation: C. Nicholas, et al.; J. Immunol. 179, 7121 (2007) Abstract
Further Categories Containing This Product:
MAPK Pathway Inhibitors • Hypoxia-inducible Factor [HIF] / Related Products • VEGFs & VEGF-Rs Other Products • Natural Products for Angiogenesis Research • Natural Products - Protein Kinase Inhibitors • Natural Products - Chemopreventive Agents • Natural Products - Antitumor Reagents • Antitumor Agents (Anti-proliferative) • Natural Products - Apoptosis Inducers & Inhibitors • Natural Products - Antioxidants • Antitumor Agents (Enzyme Inhibitors)
 
 
ALX-340-063 Revised 19-Apr-07
N-Arachidonoyl-L-serine
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SYNONYMS N-[(5Z,8Z,11Z,14Z)-1-Oxo-5,8,11,14-eicosatetraenyl)]-L-serine
ARA-S
PRODUCT LINE Neurobiology
PRODUCT CATEGORY Endocannabinoids
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ALX-340-063-M010   10 mg 90.00 USD Add To Cart
Product Specification
FORMULA: C23H37NO4
MW: 391.5
CAS NUMBER: 187224-29-9
PURITY: ≥98%
APPEARANCE: Waxy solid.
SOLUBILITY: Soluble in DMSO or dimethyl formamide; sparingly soluble in water.
SHIPPING: SHIPPED ON DRY ICE
LONG TERM STORAGE: -80°C

Product Description
Endocannabinoid-like brain constituent with similar biological profile like abnormal cannabidiol. Binds weakly to CB1 and CB2 receptors and TRPV1. Produces endothelium-dependent vasodilation. Increases phosphorylation of Akt and mitogen-activated protein kinase (MAPK) in HUVEC.
Product Specific Literature References
N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties: G. Milman, et al.; PNAS 103, 2428 (2006) Abstract; Full Text
Further Categories Containing This Product: