Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4ILYC)

• DTT Name: Bacterial Dihydropteroate synthetase (Bact folP)
• Synonyms: folP; H2Pte synthase; Dihydropteroate synthase; Dihydropteroate pyrophosphorylase; DHPS
• Gene Name: Bact folP
• DTT Type: Successful target; [1]
• BioChemical Class: Alkyl aryl transferase
• UniProt ID: DHPS_ECOLI
• TTD ID: T88240
• EC Number: EC 2.5.1.15
• Sequence:
  MKLFAQGTSLDLSHPHVMGILNVTPDSFSDGGTHNSLIDAVKHANLMINAGATIIDVGGE
  STRPGAAEVSVEEELQRVIPVVEAIAQRFEVWISVDTSKPEVIRESAKVGAHIINDIRSL
  SEPGALEAAAETGLPVCLMHMQGNPKTMQEAPKYDDVFAEVNRYFIEQIARCEQAGIAKE
  KLLLDPGFGFGKNLSHNYSLLARLAEFHHFNLPLLVGMSRKSMIGQLLNVGPSERLSGSL
  ACAVIAAMQGAHIIRVHDVKETVEAMRVVEATLSAKENKRYE
• Function: Dhps catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide.
• KEGG Pathway:
  Folate biosynthesis (ecj00790)
  Metabolic pathways (ecj01100)
  Biosynthesis of cofactors (ecj01240)
• BioCyc Pathway:
  MetaCyc:H2PTEROATESYNTH-MON
  EcoCyc:H2PTEROATESYNTH-MON

Molecular Interaction Atlas (MIA) of This DTT

22 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cefozopran	DMKBTFG	Gram-positive bacterial infection	1B74-1G40	Approved	[1]
Chlorhexidine	DMQ9MVG	Bacterial infection	1A00-1C4Z	Approved	[2]
Colistimethate	DMZ9BMU	Respiratory tract infection	CA45	Approved	[3]
Colistin	DMMD9QE	Pseudomonas infection	1B92	Approved	[3]
Daptomycin	DMFDQ3I	Bacterial infection	1A00-1C4Z	Approved	[4]
Doripenem	DM9UCJK	Cholecystitis		Approved	[1]
Faropenem	DMX7A5V	Gram-positive bacterial infection	1B74-1G40	Approved	[1]
Gramicidin D	DMPT74U	Bacterial infection	1A00-1C4Z	Approved	[5]
Oritavancin	DM28D05	Bacterial infection	1A00-1C4Z	Approved	[1]
Polymyxin B Sulfate	DMN0LP8	Bacteremia	1A73	Approved	[3]
Silver sulfadiazine	DMVTHWQ	Bacterial infection	1A00-1C4Z	Approved	[6]
Sulfacytine	DMKI2XC	Cystitis	GC00	Approved	[7]
Sulfadiazine	DMTW3R8	Rheumatic fever	1B40-1B42	Approved	[8]
Sulfamerazine	DMKM3SX	Bacterial infection	1A00-1C4Z	Approved	[9]
Sulfamethazine	DMRGZ16	Bacterial infection	1A00-1C4Z	Approved	[10]
Sulfamethizole	DMGCHDS	Acute otitis media	AB00	Approved	[11]
Sulfamethoxazole	DMB08GE	Acute otitis media	AB00	Approved	[12]
Sulfanilamide	DMABVE9	Bacterial infection	1A00-1C4Z	Approved	[13]
Sulfapyridine	DMIUYFH	Dermatitis herpetiformis	EB44	Approved	[9]
Sulfisoxazole	DMXLT8C	Acute otitis media	AB00	Approved	[14]
Sulfonamides	DM1YA7M	Bacterial infection	1A00-1C4Z	Approved	[15]
Sulphadoxine	DMZI2UF	Malaria	1F40-1F45	Approved	[16]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sulfametopyrazine	DMBCK2S	Urinary tract infection	GC08	Withdrawn from market	[17]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2,6-diamino-5-nitropyrimidin-4(3H)-one	DMREF31	Discovery agent	N.A.	Investigative	[18]
2,6-diamino-5-nitrosopyrimidin-4(3H)-one	DM4RS9N	Discovery agent	N.A.	Investigative	[18]
2-amino-8-methyl-7,8-dihydropteridin-4(3H)-one	DMRSGC5	Discovery agent	N.A.	Investigative	[18]
6-Methylamino-5-Nitroisocytosine	DMN6IDK	Discovery agent	N.A.	Investigative	[19]
Ethylene diamine	DMBULX4	Tuberculosis	1B10-1B1Z	Investigative	[20]
HKI-9924129	DM5LR2B	Gram-positive bacterial infection	1B74-1G40	Investigative	[1]
Pterin-6-Yl-Methyl-Monophosphate	DM98IOX	Discovery agent	N.A.	Investigative	[21]
Pteroic Acid	DMT2YNG	Discovery agent	N.A.	Investigative	[22]
[Pterin-6-Yl Methanyl]-Phosphonophosphate	DM4ZY79	Discovery agent	N.A.	Investigative	[21]

References

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• [14] Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63.
• [15] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [16] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [17] Plasmodium falciparum dihydrofolate reductase Val-16 and Thr-108 mutation associated with in vivo resistance to antifolate drug: a case study. Indian J Malariol. 2001 Sep-Dec;38(3-4):76-83.
• [18] Structural studies of pterin-based inhibitors of dihydropteroate synthase. J Med Chem. 2010 Jan 14;53(1):166-77.
• [19] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [20] Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
• [21] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [22] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.