| Structural highlights
Disease
[F16P1_HUMAN] Defects in FBP1 are the cause of fructose-1,6-bisphosphatase deficiency (FBPD) [MIM:229700]. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.[1] [2]
Function
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
With the goal of improving metabolic stability and further enhancing FBPase inhibitory activity, a series of tricyclic 8H-indeno[1,2-d][1,3]thiazoles was designed and synthesized with the aid of structure-based drug design. Extensive SAR studies led to the discovery of 19a with an IC(50) value of 1nM against human FBPase. X-ray crystallographic studies revealed that high affinity of 19a was due to the hydrophobic interaction arising from better shape complementarity and to the hydrogen bonding network involving the side chain on the tricyclic scaffold.
Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors.,Tsukada T, Takahashi M, Takemoto T, Kanno O, Yamane T, Kawamura S, Nishi T Bioorg Med Chem Lett. 2010 Feb 1;20(3):1004-7. Epub 2009 Dec 21. PMID:20045638[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kikawa Y, Inuzuka M, Jin BY, Kaji S, Koga J, Yamamoto Y, Fujisawa K, Hata I, Nakai A, Shigematsu Y, Mizunuma H, Taketo A, Mayumi M, Sudo M. Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency. Am J Hum Genet. 1997 Oct;61(4):852-61. PMID:9382095
- ↑ Matsuura T, Chinen Y, Arashiro R, Katsuren K, Tamura T, Hyakuna N, Ohta T. Two newly identified genomic mutations in a Japanese female patient with fructose-1,6-bisphosphatase (FBPase) deficiency. Mol Genet Metab. 2002 Jul;76(3):207-10. PMID:12126934
- ↑ Tsukada T, Takahashi M, Takemoto T, Kanno O, Yamane T, Kawamura S, Nishi T. Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors. Bioorg Med Chem Lett. 2010 Feb 1;20(3):1004-7. Epub 2009 Dec 21. PMID:20045638 doi:10.1016/j.bmcl.2009.12.056
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