Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTB4UP)

• DTT Name: Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)
• Synonyms: IMPDH-II; IMPDH 2; IMPD2; IMPD 2; IMP dehydrogenase 2
• Gene Name: IMPDH2
• DTT Type: Successful target; [1]
• BioChemical Class: CH-OH donor oxidoreductase
• UniProt ID: IMDH2_HUMAN
• TTD ID: T89360
• EC Number: EC 1.1.1.205
• Sequence:
  MADYLISGGTSYVPDDGLTAQQLFNCGDGLTYNDFLILPGYIDFTADQVDLTSALTKKIT
  LKTPLVSSPMDTVTEAGMAIAMALTGGIGFIHHNCTPEFQANEVRKVKKYEQGFITDPVV
  LSPKDRVRDVFEAKARHGFCGIPITDTGRMGSRLVGIISSRDIDFLKEEEHDCFLEEIMT
  KREDLVVAPAGITLKEANEILQRSKKGKLPIVNEDDELVAIIARTDLKKNRDYPLASKDA
  KKQLLCGAAIGTHEDDKYRLDLLAQAGVDVVVLDSSQGNSIFQINMIKYIKDKYPNLQVI
  GGNVVTAAQAKNLIDAGVDALRVGMGSGSICITQEVLACGRPQATAVYKVSEYARRFGVP
  VIADGGIQNVGHIAKALALGASTVMMGSLLAATTEAPGEYFFSDGIRLKKYRGMGSLDAM
  DKHLSSQNRYFSEADKIKVAQGVSGAVQDKGSIHKFVPYLIAGIQHSCQDIGAKSLTQVR
  AMMYSGELKFEKRTSSAQVEGGVHSLHSYEKRLF
• Function: Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors. Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)
• BioCyc Pathway: MetaCyc:HS11242-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[1]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Urea and carbamate bioisostere derivative 1	DMEQFXZ	N. A.	N. A.	Patented	[2]

31 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(3-cyano-1-methyl-1H-indol-6-yl)-3-phenylurea	DM8DR1B	Discovery agent	N.A.	Investigative	[3]
1-methoxy-3-(3-(pyridin-4-yl)-1H-indol-6-yl)urea	DM7DTRM	Discovery agent	N.A.	Investigative	[3]
1-methyl-1H-indole-3-carbaldehyde	DMDZ1FR	Discovery agent	N.A.	Investigative	[4]
1-methyl-1H-indole-3-carbonitrile	DML5FQT	Discovery agent	N.A.	Investigative	[3]
1-methyl-1H-indole-3-carboxamide	DMUKAH6	Discovery agent	N.A.	Investigative	[4]
2-Benzyl-6-methoxy-5-oxazol-5-yl-1H-indole	DMGWRID	Discovery agent	N.A.	Investigative	[5]
2-methyl-3-(pyridin-4-yl)-1H-indol-6-amine	DMV8YIZ	Discovery agent	N.A.	Investigative	[4]
2-methyl-3-(pyridin-4-yl)-1H-indole	DM8N54C	Discovery agent	N.A.	Investigative	[4]
3-(3-cyano-1H-indol-6-yl)-1-methyl-1-phenylurea	DMGJS9N	Discovery agent	N.A.	Investigative	[3]
3-(furan-3-yl)-1-methyl-1H-indole	DM6L4J8	Discovery agent	N.A.	Investigative	[4]
3-(furan-3-yl)-1H-indole	DMM2AR3	Discovery agent	N.A.	Investigative	[4]
3-(pyridin-4-yl)-1H-indol-6-amine	DMZARSD	Discovery agent	N.A.	Investigative	[4]
3-(pyridin-4-yl)-1H-indol-7-amine	DMRFPNE	Discovery agent	N.A.	Investigative	[4]
3-(thiophen-3-yl)-1H-indol-6-amine	DMMI0UC	Discovery agent	N.A.	Investigative	[4]
3-methoxy-4-(oxazol-5-yl)aniline	DMKUM4L	Discovery agent	N.A.	Investigative	[4]
6-bromo-1-methyl-3-(pyridin-4-yl)-1H-indole	DMM9GOR	Discovery agent	N.A.	Investigative	[4]
6-bromo-3-(pyridin-4-yl)-1H-indole	DMVWX62	Discovery agent	N.A.	Investigative	[4]
6-Chloropurine Riboside, 5'-Monophosphate	DMWB43U	Discovery agent	N.A.	Investigative	[6]
6-Methoxy-5-oxazol-5-yl-2-phenyl-1H-indole	DMHO7TZ	Discovery agent	N.A.	Investigative	[5]
6-phenyl-3-(pyridin-4-yl)-1H-indole	DM3UBR5	Discovery agent	N.A.	Investigative	[3]
C2-MAD	DMS87IF	Discovery agent	N.A.	Investigative	[7]
C4-MAD	DMGA9U7	Discovery agent	N.A.	Investigative	[7]
Ethyl 3-(pyridin-4-yl)-1H-indole-6-carboxylate	DM4UWYF	Discovery agent	N.A.	Investigative	[3]
Inosinic Acid	DMLR86H	Discovery agent	N.A.	Investigative	[6]
Mycophenolic bis(sulfonamide)	DMUQP3J	Discovery agent	N.A.	Investigative	[8]
Mycophenolic hydroxamic acid	DM4YRAH	Discovery agent	N.A.	Investigative	[9]
N-benzyl-9-oxo-9,10-dihydroacridine-3-carboxamide	DMDRE64	Discovery agent	N.A.	Investigative	[10]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[6]
Rockout	DMOTPJD	Discovery agent	N.A.	Investigative	[3]
Selenazole-4-Carboxyamide-Adenine Dinucleotide	DMXERWD	Discovery agent	N.A.	Investigative	[6]
Tiazofurin adenine dinucleotide	DMEFVPH	Discovery agent	N.A.	Investigative	[11]

References

• [1] Clinical pipeline report, company report or official report of Roche (2009).
• [2] Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors: a patent and scientific literature review (2002-2016).Expert Opin Ther Pat. 2017 Jun;27(6):677-690.
• [3] Novel indole inhibitors of IMPDH from fragments: synthesis and initial structure-activity relationships. Bioorg Med Chem Lett. 2006 May 1;16(9):2539-42.
• [4] Low molecular weight indole fragments as IMPDH inhibitors. Bioorg Med Chem Lett. 2006 May 1;16(9):2535-8.
• [5] Novel indole-based inhibitors of IMPDH: introduction of hydrogen bond acceptors at indole C-3. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1273-6.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia. J Med Chem. 2002 Jan 31;45(3):703-12.
• [8] Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase. Bioorg Med Chem. 2008 Aug 1;16(15):7462-9.
• [9] Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase and differentiation induction of K562 cells among the mycoph... Bioorg Med Chem. 2010 Nov 15;18(22):8106-11.
• [10] Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1... J Med Chem. 2007 Jul 26;50(15):3730-42.
• [11] Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment. J Med Chem. 2007 Dec 27;50(26):6685-91.