Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMS54D)

• DTT Name: Fragile histidine triad protein (FHIT)
• Synonyms: Fragile histidinetriad protein; Fragile histidinetriad (FHIT) gene; Dinucleosidetriphosphatase; Diadenosine 5',5'''-P1,P3-triphosphate hydrolase; Bis(5'-adenosyl)-triphosphatase; AP3AASE; AP3A hydrolase
• Gene Name: FHIT
• DTT Type: Successful target; [1]
• BioChemical Class: Acid anhydride hydrolase
• UniProt ID: FHIT_HUMAN
• TTD ID: T59720
• EC Number: EC 3.6.1.29
• Sequence:
  MSFRFGQHLIKPSVVFLKTELSFALVNRKPVVPGHVLVCPLRPVERFHDLRPDEVADLFQ
  TTQRVGTVVEKHFHGTSLTFSMQDGPEAGQTVKHVHVHVLPRKAGDFHRNDSIYEELQKH
  DKEDFPASWRSEEEMAAEAAALRVYFQ
• Function: Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity, it may in part come from the mitochondrial form, which sensitizes the low-affinity Ca(2+) transporters, enhancing mitochondrial calcium uptake. Functions as tumor suppressor. Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fructose	DM43AN2	Vomiting	MD90	Approved	[1]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adenosine Monotungstate	DMJZPSX	Discovery agent	N.A.	Investigative	[1]
Ado-P-Ch2-P-Ps-Ado	DM9IBHU	Discovery agent	N.A.	Investigative	[1]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Dinucleosidetriphosphatase (FHIT) DME Info
• Gene Name: FHIT

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adenylylsulfate	DM0YQ2I	N. A.	N. A.	Investigative	[2]

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] Adenylylsulfate-ammonia adenylyltransferase activity is another inherent property of Fhit proteins. Biosci Rep. 2015 Jun 25;35(4). pii: e00235.