109944-15-2 Usage
Description
Kifunensine, an alkaloid derived from the fungus Kitasatosporia kifunense, is a potent inhibitor of the glycoprotein processing enzyme mannosidase I. It is a unique oxamide derivative of mannojirimycin and has been shown to be a weak inhibitor of aryl mannosidase. Kifunensine is effective in inhibiting human endoplasmic reticulum α-1,2-mannosidase I and Golgi Class I mannosidases IA, IB, and IC. It is a white powder in appearance and has immunomodulating properties.
Uses
1. Used in Pharmaceutical Industry:
Kifunensine is used as an inhibitor of mannosidase I for its potential therapeutic applications in various diseases. Its inhibition of glycoprotein processing can be beneficial in the treatment of conditions related to the misfolding of proteins.
2. Used in Research and Development:
Kifunensine is used as a research tool for studying the role of mannosidase I in cellular processes and its potential as a target for therapeutic intervention.
3. Used in Drug Design and Development:
Kifunensine's potent inhibition of mannosidase I makes it a valuable compound in the design and development of new drugs targeting this enzyme for various therapeutic applications.
4. Used in the Treatment of Limb Girdle Muscular Dystrophy Type 2D:
Kifunensine is used as a pharmacological approach for patients carrying mutations that impair α-sarcoglycan trafficking, as its inhibition of endoplasmic reticulum α-mannosidase I activity can rescue the human α-sarcoglycan R77C mutation.
5. Used in Improving Maturation of Misfolded Proteins:
Kifunensine is used to enhance the maturation of misfolded proteins, which can be beneficial in the treatment of diseases caused by protein misfolding.
Biological Activity
Inhibitor of class I α -mannosidases that inhibits glycoprotein processing. Inhibits human endoplasmic reticulum α -1,2-mannosidase I and Golgi Class I mannosidases IA, IB and IC with K i values of 130 and 23 nM respectively.
Biochem/physiol Actions
Product does not compete with ATP.
References
1)?Iwami et al. (1987), A new immunomodulator, FR-900494: taxonomy, fermentation, isolation, and physico-chemical and biological characteristics; J.Antibiot. (Tokyo) 40 612
2)?Elbein et al. (1990), Kifunensine, a potent inhibitor of the glycoprotein processing mannosidase I; ?J.Biol.Chem. 265 15599
3)?Bartoli et al. (2008), Mannosidase I inhibition rescues the human alpha-sarcoglycan R77C recurrent mutation; ?Hum.Mol.Genet. 17 1214
4)?Wang et al. (2011), Inhibition of endoplasmic reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases; J.Biol.Chem. 286 43454
Check Digit Verification of cas no
The CAS Registry Mumber 109944-15-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,9,9,4 and 4 respectively; the second part has 2 digits, 1 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 109944-15:
(8*1)+(7*0)+(6*9)+(5*9)+(4*4)+(3*4)+(2*1)+(1*5)=142
142 % 10 = 2
So 109944-15-2 is a valid CAS Registry Number.
InChI:InChI=1/C8H12N2O6/c11-1-2-3(12)4(13)5(14)6-9-7(15)8(16)10(2)6/h2-6,11-14H,1H2,(H,9,15)/t2-,3-,4+,5+,6+/m1/s1
109944-15-2Relevant articles and documents
Total Synthesis of (+)-Kifunensine, a Potent Glycosidase Inhibitor
Rouden, Jacques,Hudlicky, Tomas
, p. 1095 - 1098 (1993)
(+)-Kifunensine, a potent inhibitor of mannosidase I, has been synthesized in 13 steps from chlorobenzene by microbial oxygenation with Pseudomonas putida 39D and stereocontrolled peripheral functionalization of cis-3-chlorocylohexa-3,5-dienediol 3.
A practical synthesis of kifunensine analogues as inhibitors of endoplasmic reticulum α-mannosidase I
Hering, Kirk W.,Karaveg, Khanita,Moremen, Kelley W.,Pearson, William H.
, p. 9892 - 9904 (2007/10/03)
A practical synthesis of the potent class I α-mannosidase inhibitor kifunensine (1) beginning from the inexpensive and readily available starting material L-ascorbic acid (15) is described. The protected amino-alcohol ((2R,3R,4R,5R)-5-amino-2,3:4,6-diisop
Synthesis of kifunensine, an immunomodulating substance isolated from a microbial source
Kayakiri,Kasahara,Nakamura,Oku,Hashimoto
, p. 1392 - 1396 (2007/10/02)
Kifunensine (1), a novel immunomodulator isolated from an actinomycete, was enantiospecifically synthesized from D-mannosamine via a double cyclization of the oxamide-aldehyde precursor with ammonia as a key step. The absolute stereochemistry of natural kifunensine was confirmed to be the D form.
