Target Information
| Target General Information | Top | |||||
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| Target ID |
T83391
(Former ID: TTDC00152)
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| Target Name |
Fructose-1,6-bisphosphatase (FBP)
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| Synonyms |
FBPase; D-fructose-1,6-bisphosphate 1-phosphohydrolase
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| Gene Name |
FBP1; FBP2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Type 2 diabetes mellitus [ICD-11: 5A11] | |||||
| Function |
Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain.
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| BioChemical Class |
Phosphoric monoester hydrolase
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| UniProt ID | ||||||
| Sequence |
MADQAPFDTDVNTLTRFVMEEGRKARGTGELTQLLNSLCTAVKAISSAVRKAGIAHLYGI
AGSTNVTGDQVKKLDVLSNDLVMNMLKSSFATCVLVSEEDKHAIIVEPEKRGKYVVCFDP LDGSSNIDCLVSVGTIFGIYRKKSTDEPSEKDALQPGRNLVAAGYALYGSATMLVLAMDC GVNCFMLDPAIGEFILVDKDVKIKKKGKIYSLNEGYARDFDPAVTEYIQRKKFPPDNSAP YGARYVGSMVADVHRTLVYGGIFLYPANKKSPNGKLRLLYECNPMAYVMEKAGGMATTGK EAVLDVIPTDIHQRAPVILGSPDDVLEFLKVYEKHSAQ Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | Managlinat dialanetil | Drug Info | Phase 2 | Type-2 diabetes | [2] | |
| 2 | MB07803 | Drug Info | Phase 2 | Type-2 diabetes | [3], [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Managlinat dialanetil | Drug Info | [1] | |||
| 2 | MB07803 | Drug Info | [5] | |||
| Inhibitor | [+] 10 Inhibitor drugs | + | ||||
| 1 | 1-(2-mercaptoethyl)-3-(m-tolylsulfonyl)urea | Drug Info | [6] | |||
| 2 | 1-(4-aminophenylsulfonyl)-3-(2-mercaptoethyl)urea | Drug Info | [6] | |||
| 3 | 2,5-Anhydroglucitol-1,6-Biphosphate | Drug Info | [7] | |||
| 4 | 2-(4-(4-Hydroxyphenyl)thiazol-2-ylamino)phenol | Drug Info | [8] | |||
| 5 | 3-(4-(4-Hydroxyphenyl)thiazol-2-ylamino)phenol | Drug Info | [8] | |||
| 6 | 4,6-Dichloro-1H-indole-2-carboxylic acid | Drug Info | [9] | |||
| 7 | 4-(2-amino-1,3-thiazol-4-yl)phenol | Drug Info | [8] | |||
| 8 | 4-(4-(4-Nitrophenyl)thiazol-2-ylamino)phenol | Drug Info | [8] | |||
| 9 | Fructose-6-Phosphate | Drug Info | [7] | |||
| 10 | N-(5-chlorobenzo[d]oxazol-2-yl)benzenesulfonamide | Drug Info | [10] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | Gluconeogenesis | |||||
| KEGG Pathway | [+] 9 KEGG Pathways | + | ||||
| 1 | Glycolysis / Gluconeogenesis | |||||
| 2 | Pentose phosphate pathway | |||||
| 3 | Fructose and mannose metabolism | |||||
| 4 | Metabolic pathways | |||||
| 5 | Biosynthesis of antibiotics | |||||
| 6 | Carbon metabolism | |||||
| 7 | AMPK signaling pathway | |||||
| 8 | Insulin signaling pathway | |||||
| 9 | Glucagon signaling pathway | |||||
| Pathwhiz Pathway | [+] 3 Pathwhiz Pathways | + | ||||
| 1 | Fructose and Mannose Degradation | |||||
| 2 | Pentose Phosphate Pathway | |||||
| 3 | Gluconeogenesis | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Gluconeogenesis | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Glycolysis and Gluconeogenesis | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes. Proc Natl Acad Sci U S A. 2005 May 31;102(22):7970-5. | |||||
| REF 2 | ClinicalTrials.gov (NCT00290940) Evaluation of Glucose Lowering Effect, Safety and Tolerability of CS-917. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT00458016) Safety, Tolerability, and Efficacy Study of MB07803 Administered to Patients With Type 2 Diabetes Mellitus. U.S. National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 6 | Allosteric FBPase inhibitors gain 10(5) times in potency when simultaneously binding two neighboring AMP sites. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4708-12. | |||||
| REF 7 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 8 | A library of novel allosteric inhibitors against fructose 1,6-bisphosphatase. Bioorg Med Chem. 2009 Jun 1;17(11):3916-22. | |||||
| REF 9 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 10 | Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1807-10. | |||||
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