Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWHDVK)

• DTT Name: Fructose-1,6-bisphosphatase (FBP)
• Synonyms: FBPase; D-fructose-1,6-bisphosphate 1-phosphohydrolase
• Gene Name: FBP1; FBP2
• DTT Type: Clinical trial target; [1]
• Related Disease: Type 2 diabetes mellitus [ICD-11: 5A11]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: F16P1_HUMAN ; F16P2_HUMAN
• TTD ID: T83391
• Sequence:
  MADQAPFDTDVNTLTRFVMEEGRKARGTGELTQLLNSLCTAVKAISSAVRKAGIAHLYGI
  AGSTNVTGDQVKKLDVLSNDLVMNMLKSSFATCVLVSEEDKHAIIVEPEKRGKYVVCFDP
  LDGSSNIDCLVSVGTIFGIYRKKSTDEPSEKDALQPGRNLVAAGYALYGSATMLVLAMDC
  GVNCFMLDPAIGEFILVDKDVKIKKKGKIYSLNEGYARDFDPAVTEYIQRKKFPPDNSAP
  YGARYVGSMVADVHRTLVYGGIFLYPANKKSPNGKLRLLYECNPMAYVMEKAGGMATTGK
  EAVLDVIPTDIHQRAPVILGSPDDVLEFLKVYEKHSAQ
• 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.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Pentose phosphate pathway (hsa00030)
  Fructose and mannose metabolism (hsa00051)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
  Carbon metabolism (hsa01200)
  AMPK signaling pathway (hsa04152)
  Insulin signaling pathway (hsa04910)
  Glucagon signaling pathway (hsa04922)
• Reactome Pathway: Gluconeogenesis (R-HSA-70263)
• BioCyc Pathway: MetaCyc:HS09189-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Managlinat dialanetil	DMBYDNE	Type-2 diabetes	5A11	Phase 2	[1]
MB07803	DMHU8SJ	Type-2 diabetes	5A11	Phase 2	[2]

10 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(2-mercaptoethyl)-3-(m-tolylsulfonyl)urea	DMIPAMW	Discovery agent	N.A.	Investigative	[3]
1-(4-aminophenylsulfonyl)-3-(2-mercaptoethyl)urea	DM4G0NH	Discovery agent	N.A.	Investigative	[3]
2,5-Anhydroglucitol-1,6-Biphosphate	DMLDHMB	Discovery agent	N.A.	Investigative	[4]
2-(4-(4-Hydroxyphenyl)thiazol-2-ylamino)phenol	DMOYT8I	Discovery agent	N.A.	Investigative	[5]
3-(4-(4-Hydroxyphenyl)thiazol-2-ylamino)phenol	DM8EH07	Discovery agent	N.A.	Investigative	[5]
4,6-Dichloro-1H-indole-2-carboxylic acid	DM62XC3	Discovery agent	N.A.	Investigative	[6]
4-(2-amino-1,3-thiazol-4-yl)phenol	DMH5CAQ	Discovery agent	N.A.	Investigative	[5]
4-(4-(4-Nitrophenyl)thiazol-2-ylamino)phenol	DMA9TCD	Discovery agent	N.A.	Investigative	[5]
Fructose-6-phosphate	DMU5SAF	Discovery agent	N.A.	Investigative	[4]
N-(5-chlorobenzo[d]oxazol-2-yl)benzenesulfonamide	DM2TFJE	Discovery agent	N.A.	Investigative	[7]

References

• [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.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [3] 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.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] A library of novel allosteric inhibitors against fructose 1,6-bisphosphatase. Bioorg Med Chem. 2009 Jun 1;17(11):3916-22.
• [6] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [7] Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1807-10.