ProHealth health Vitamin and Natural Supplement Store and Health
Home  |  Log In  |  My Account  |  View Cart  View Your ProHealth Vitamin and Supplement Shopping Cart
800-366-6056  |  Contact Us  |  Help
Facebook Google Plus
Fibromyalgia  Chronic Fatigue Syndrome & M.E.  Lyme Disease  Natural Wellness  Supplement News  Forums  Our Story
Store     Brands   |   A-Z Index   |   Best Sellers   |   New Products   |   Deals & Specials   |   Under $10   |   SmartSavings Club

Trending News

B Vitamins May Protect Against Damaging Effects of Air Pollution, and Improve Cognition and Psychiat...

Relief for IBS, Colitis, Crohn’s And More

Can Magnesium Relieve Your Tinnitus?

Resveratrol Proven to Slow Brain Aging

Magnesium Protects Against Stroke, Heart Disease and Diabetes

Fruits and vegetables' latest superpower? Lowering blood pressure

Neroli Oil: The Pleasantly Fragrant Citrus Oil

Restoring NAD+ could reduce DNA damage accumulation

What Benefits Can You Derive From Patchouli Oil?

Astaxanthin Is a Longevity Promoter

 
Print Page
Email Article

Abstract: Structural insights and biological effects of glycogen synthase kinase 3 specific inhibitor AR-A014418

  [ 46 votes ]   [ Discuss This Article ]
www.ProHealth.com • September 17, 2003


J Biol Chem. 2003 Aug 19 [Epub ahead of print].

Bhat RV, Xue Y, Berg S, Hellberg (1) S, Ormo M, Nilsson Y, Radesater AC, Jerning E, Markgren PO, Borgegard T, Nylof M, Gimenez-Cassina A, Hernandez F, Lucas JJ, Diaz-Nido J, Avila J.

Research DMPK, AstraZeneca RD Sdertlje, Sdertlje 15185.

Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that has been implicated in pathological conditions such as diabetes and Alzheimer's disease. We report the characterization of a GSK3 inhibitor, AR-A014418, which inhibits GSK3 (IC50 104+27 nM), in an ATP competitive manner (Ki, 38 nM). AR-A014418 does not significantly inhibit cdk2 or cdk5 (IC50 > 100 mM) or 26 other kinases demonstrating high specificity for GSK3.

We report the co-crystallisation of AR-A014418 with the GSK3beta protein and provide a description of the interactions within the ATP pocket as well as an understanding of the structural basis for the selectivity of AR-A014418. AR-A014418 inhibits tau phosphorylation at a GSK3 specific site (Ser-396) in cells stably expressing human 4-repeat tau protein.

AR-A014418 protects N2A neuroblastoma cells against cell death mediated by inhibition of the PI3K/PKB survival pathway. Furthermore, AR-A014418 inhibits neurodegeneration mediated by beta-amyloid peptide in hippocampal slices. AR-A014418 may thus have important applications as a tool to elucidate the role of GSK3 in cellular signaling and possibly in Alzheimers disease. AR-A014418 is the first compound of a family of specific inhibitors of GSK3 that does not significantly inhibit closely related kinases such as cdk2 or cdk5.

PMID: 12928438 [PubMed - as supplied by publisher]




Post a Comment

Featured Products From the ProHealth Store
Energy NADH™ 12.5mg FibroSleep™ Ultra EPA  - Fish Oil

Looking for Vitamins, Herbs and Supplements?
Search the ProHealth Store for Hundreds of Natural Health Products


Article Comments



Be the first to comment on this article!

Post a Comment


 
NAD+ Ignite with Niagen

Featured Products

Energy NADH™ 12.5mg Energy NADH™ 12.5mg
Improve Energy & Cognitive Function
FibroSleep™ FibroSleep™
The All-in-One Natural Sleep Aid
Optimized Curcumin Longvida® Optimized Curcumin Longvida®
Supports Cognition, Memory & Overall Health
Mitochondria Ignite™ with NT Factor® Mitochondria Ignite™ with NT Factor®
Reduce Fatigue up to 45%
Vitamin D3 Extreme™ Vitamin D3 Extreme™
50,000 IU Vitamin D3 - Prescription Strength

Natural Remedies

Itching to Find Dry Skin Relief? Itching to Find Dry Skin Relief?
Can Glycine + Amino Acids Be the Secret to Deep, Rejuvenating Sleep? Can Glycine + Amino Acids Be the Secret to Deep, Rejuvenating Sleep?
Vitamin K-2 – A Key Player in Cardiovascular and Bone Health Vitamin K-2 – A Key Player in Cardiovascular and Bone Health
Nutrients to Combat the Modern Stress Epidemic Nutrients to Combat the Modern Stress Epidemic
Coenzyme Q10 - The Energy Maker Coenzyme Q10 - The Energy Maker

CONTACT US
ProHealth, Inc.
555 Maple Ave
Carpinteria, CA 93013
(800) 366-6056  |  Email

· Become a Wholesaler
· Vendor Inquiries
· Affiliate Program
SHOP WITH CONFIDENCE
Credit Card Processing
SUBSCRIBE TO OUR NEWSLETTERS
Get the latest news about Fibromyalgia, M.E/Chronic Fatigue Syndrome, Lyme Disease and Natural Wellness

CONNECT WITH US ProHealth on Facebook  ProHealth on Twitter  ProHealth on Pinterest  ProHealth on Google Plus

© 2017 ProHealth, Inc. All rights reserved. Pain Tracker App  |  Store  |  Customer Service  |  Guarantee  |  Privacy  |  Contact Us  |  Library  |  RSS  |  Site Map