ALEXIS Biochemicals: (+)-Madindoline A

ALX-350-328

Revised 07-Apr-08

(+)-Madindoline A
SYNONYMS	MadA MDL-A [(2R), 3aR, 8aS]-8-[4-(n-Butyl)-2,5-dimethyl-1, 3-dioxo-2-(4-cyclopentyl)methyl]-3, 3a, 8,8a-tetrahydro-3a-hydroxy-2H-furo[2,3-b] indole
PRODUCT LINE	Chemokines & Cytokines
PRODUCT CATEGORY	Interleukin & Interleukin Receptors Other Products

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-350-328-MC05		0.5 mg	330.00 USD
ALX-350-328-M001		1 mg	580.00 USD

Product Specification

FORMULA:	C₂₂H₂₇NO₄
MW:	370.2
SOURCE/HOST:	Synthetic.
PURITY:	≥97%
APPEARANCE:	Light yellow needles
SOLUBILITY:	Soluble in methanol or 100% ethanol; insoluble in hexane.
SHIPPING:	AMBIENT
LONG TERM STORAGE:	-20°C

Product Description

Madindolines are noncytotoxic indole alkaloids originally isolated from a fermentation broth of Streptomyces nitrosporeus K93-071. (+)-Madindoline A (MadA; MDL-A) and (+)-madindoline B (MadB; MDL-B) are diastereomers with MadA being the more potent compound. MadA binds competitively but noncovalently to the extracellular domain of the membrane glycoprotein gp130 and inhibits the homodimerization of the trimeric IL-6/IL-6R/gp130 or the IL-11/gp130 complex, thus inhibiting activation of the JAK/STAT signal transduction pathway. MadA inhibits IL-6 and IL-11-induced osteoclastogenesis in vitro in a dose dependent manner and postmenopausal osteoporosis in vivo, by a mechanism different from that of 17β-estradiol. IL-6 activity is known to cause various diseases such as cancer cachexia, Castleman’s disease, Crohn’s disease, rheumatoid arthritis, hypercalcemia, and multiple myeloma. Madindolines are no longer available from natural sources due to mutation of the originating bacterial strain. Thus, synthetic routes have been developed to produce madindolines. Recently analogs of madindolines have been synthesized as potent IL-6 inhibitors.

Product Specific Literature References

Madindoline, a novel inhibitor of IL-6 activity from Streptomyces sp. K93-0711. I. Taxonomy, fermentation, isolation and biological activities: M. Hayashi, et al.; J. Antibiot. 49, 1091 (1996) Abstract
Madindolines, novel inhibitors of IL-6 activity from streptomyces sp. K93-0711. II. Physico-chemical properties and structural elucidation: S.Takamatsu, et. al.; J. Antibiot. 50, 1069 (1997) Abstract
Binding of madindoline A to the extracellular domain of gp130: A.Z. Saleh, et al.; Biochemistry 44, 10822 (2005) Abstract
Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130: C. Lutticken, et al.; Science 263, 89 (1994) Abstract
Suppression of bone resorption by madindoline A, a novel nonpeptide antagonist to gp130: M. Hayashi, et al.; PNAS 99, 14728 (2002) Abstract
Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor: G. Strassmann, et.al.; J. Immunol. 150, 2341 (1993) Abstract
Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease: K. Yoshizaki, et al.; Blood 74, 1360 (1989) Abstract
Inhibition of IL-6 for the treatment of inflammatory diseases: N. Nishimoto & T. Kishimoto; Curr. Opin. Pharmacol. 4, 386 (2004) Abstract
Blockage of interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis: N. Takagi, et al.; Arthritis Rheum. 41, 2117 (1998) Abstract
Interleukin-6 enhances hypercalcemia and bone resorption mediated by parathyroid hormone-related protein in vivo: J. de la Mata, et al.; J. Clin. Invest. 95, 2846 (1995) Abstract
Granulocyte-macrophage colony-stimulating factor synergizes with interleukin-6 in supporting the proliferation of human myeloma cells: X.G. Zhang, et al.; Blood 76, 2599 (1990) Abstract
Synthesis of (+)-madindoline A and (+)-madindoline B: L. Wan & M.A. Tius; Org. Lett. 9, 647 (2007) Abstract
Design, synthesis, and biological activities of madindoline analogues: D. Yamamoto, et al.; Bioorg. Med. Chem. Lett. 16, 2807 (2006) Abstract
Efficient total synthesis of novel bioactive microbial metabolites: T. Sunazuka, et al.; Acc. Chem. Res. 41, 302 (2008) Abstract

General Information

MANUFACTURER

Manufactured by the Kitasato Institute, Tokyo.

Further Categories Containing This Product:

Natural Products - Other Signal Transduction Pathway Modulators • Bone Metabolism Other Products • Alkaloids