Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:28:11 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2960
Identification
Common NameMycophenolic acid
ClassSmall Molecule
DescriptionMycophenolic acid is an an immunosuppresant drug and potent anti-proliferative, and can be used in place of the older anti-proliferative azathioprine. It is usually used as part of triple therapy including a calcineurin inhibitor (ciclosporin or tacrolimus) and prednisolone. It is also useful in research for the selection of animal cells that express the E. coli gene coding for XGPRT (xanthine guanine phosphoribosyltransferase).
Compound Type
  • Antibiotic, Antineoplastic
  • Drug
  • Enzyme Inhibitor
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(e)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid
Acide mycophenolique
Acido micofenolico
Acidum mycophenolicum
Melbex
Micofenolico acido
Mycophenoic acid
Mycophenolate
Mycophenolsaeure
Myfortic
Chemical FormulaC17H20O6
Average Molecular Mass320.337 g/mol
Monoisotopic Mass320.126 g/mol
CAS Registry Number24280-93-1
IUPAC Name(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
Traditional Namemycophenolic acid
SMILES[H]C(CC1=C(O)C2=C(COC2=O)C(C)=C1OC)=C(C)CCC(O)=O
InChI IdentifierInChI=1S/C17H20O6/c1-9(5-7-13(18)19)4-6-11-15(20)14-12(8-23-17(14)21)10(2)16(11)22-3/h4,20H,5-8H2,1-3H3,(H,18,19)/b9-4+
InChI KeyInChIKey=HPNSFSBZBAHARI-RUDMXATFSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phthalides. Phthalides are compounds containing a 3-hydrocarbylidene-2-benzofuran-1(3H)-one moiety,.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsocoumarans
Sub ClassIsobenzofuranones
Direct ParentPhthalides
Alternative Parents
Substituents
  • Phthalide
  • Anisole
  • Medium-chain fatty acid
  • Alkyl aryl ether
  • Branched fatty acid
  • Methyl-branched fatty acid
  • Heterocyclic fatty acid
  • Hydroxy fatty acid
  • Dicarboxylic acid or derivatives
  • Fatty acyl
  • Fatty acid
  • Benzenoid
  • Unsaturated fatty acid
  • Vinylogous acid
  • Carboxylic acid ester
  • Lactone
  • Ether
  • Oxacycle
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Liver
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point141°C
Boiling PointNot Available
SolubilityInsoluble
LogP2.8
Predicted Properties
PropertyValueSource
Water Solubility0.035 g/LALOGPS
logP2.36ALOGPS
logP3.53ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)3.57ChemAxon
pKa (Strongest Basic)-4.1ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area93.06 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity85.23 m³·mol⁻¹ChemAxon
Polarizability32.95 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0bvm-0091000000-bb41ce2ccd5996f6c67cView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-002b-3128900000-5379558b00ac276e7fc2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0udi-0019000000-01d925bb1f9079308d85View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-0091000000-22fc916594dbab851293View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-0940000000-84f4c65c2cd8b7358b78View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-0593000000-1fed07ad435ca0bd7249View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0udi-0249000000-bd1d2df9c9ae8a17841fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-002r-0490000000-99420edc8894323b59c3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-0009000000-b99d88ff2ddeb6977c4aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-0149000000-ed6b854b4f9af495c8d8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0972000000-12d0e80f109d1fa6eb11View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0950000000-2e6c3543fe3f9f4e0790View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0930000000-e7a74fbe76e7141ec5f3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-022c-0910000000-27f7c0023a8b7e5b4d66View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-0009000000-4aba5ee4ba77899b36fbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-0149000000-497b49ab395f3319c943View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0971000000-68634f04b665bb0e68a3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0950000000-37f2ee0320d2ec560b93View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0f6x-0930000000-500359a3fd82c686ff99View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-006x-0900000000-6d04c3395aae26f88529View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-002r-0590000000-fe2f27357ba775714c5aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0fk9-0169000000-8ac1fec528501fa1c885View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0rmi-4192000000-ec1fc3aacbfa34ce9caaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9250000000-93b72d09ba1c362a0809View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0039000000-c3557e0d3c1a6aeeb587View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0690-2197000000-4c49dc321b035b072f67View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9381000000-0998ac034d01d840f5deView in MoNA
Toxicity Profile
Route of ExposureBioavailability following oral administration of Myfortic delayed-release tablet ranges from 70-95%
Mechanism of ToxicityMycophenolic acid is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, mycophenolic acid has potent cytostatic effects on lymphocytes. Mycophenolic acid inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of mycophenolic acid on lymphocytes. Mycophenolic acid also suppresses antibody formation by B-lymphocytes. Mycophenolic acid prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.
MetabolismMycophenolic acid is metabolized mainly by glucuronyl transferase to glucuronidated metabolites, predominantly the phenolic glucuronide, mycophenolic acid glucuronide (MPAG). MPAG does not manifest pharmacological activity. The acyl glucuronide minor metabolite has pharmacological activity similar to mycophenolic acid. The AUC ratio of Mycophenolic acid:MPAG:acyl glucuronide is approximately 1:24:0.28 at steady state. Half Life: The mean elimination half-life for mycophenolic acid ranges from 8-16 hours, while that of the MPAG metabolite ranges from 13-17 hours.
Toxicity ValuesLD50: 352 mg/kg (Oral, Rat) (2) LD50: 1000 mg/kg (Oral, Mouse) (2) LD50: >6000 mg/kg (Oral, Rabbit) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsPossible signs and symptoms of acute overdose could include the following: hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea and vomiting, and dyspepsia.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01024
HMDB IDHMDB15159
PubChem Compound ID446541
ChEMBL IDCHEMBL866
ChemSpider ID393865
KEGG IDC20380
UniProt IDNot Available
OMIM ID
ChEBI ID168396
BioCyc IDNot Available
CTD IDNot Available
Stitch IDMycophenolic acid
PDB IDMOA
ACToR IDNot Available
Wikipedia LinkMycophenolic_acid
References
Synthesis Reference

Bernard J. Abbott, John G. Whitney, “Method of preparing mycophenolic acid glucoside.” U.S. Patent US4234684, issued January, 1976.

MSDSLink
General References
  1. Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, Taylor RS: Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study. Health Technol Assess. 2005 May;9(21):1-179, iii-iv. [15899149 ]
  2. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  3. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Rna binding
Specific Function:
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. 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.
Gene Name:
IMPDH2
Uniprot ID:
P12268
Molecular Weight:
55804.495 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.006 uMNot AvailableBindingDB 19264
Inhibitory0.007 uMNot AvailableBindingDB 19264
Inhibitory0.01 uMNot AvailableBindingDB 19264
IC500.011 uMNot AvailableBindingDB 19264
IC500.012 uMNot AvailableBindingDB 19264
IC500.014 uMNot AvailableBindingDB 19264
IC500.015 uMNot AvailableBindingDB 19264
IC500.016 uMNot AvailableBindingDB 19264
IC500.0248 uMNot AvailableBindingDB 19264
IC500.0251 uMNot AvailableBindingDB 19264
IC500.63 uMNot AvailableBindingDB 19264
IC501.5 uMNot AvailableBindingDB 19264
References
  1. Vannozzi F, Filipponi F, Di Paolo A, Danesi R, Urbani L, Bocci G, Catalano G, De Simone P, Mosca F, Del Tacca M: An exploratory study on pharmacogenetics of inosine-monophosphate dehydrogenase II in peripheral mononuclear cells from liver-transplant recipients. Transplant Proc. 2004 Nov;36(9):2787-90. [15621150 ]
  2. Wang J, Zeevi A, Webber S, Girnita DM, Addonizio L, Selby R, Hutchinson IV, Burckart GJ: A novel variant L263F in human inosine 5'-monophosphate dehydrogenase 2 is associated with diminished enzyme activity. Pharmacogenet Genomics. 2007 Apr;17(4):283-90. [17496727 ]
  3. Penuelas S, Noe V, Morales R, Ciudad CJ: Sensitization of human erythroleukemia K562 cells resistant to methotrexate by inhibiting IMPDH. Med Sci Monit. 2005 Jan;11(1):BR6-12. [15614187 ]
  4. Yam P, Jensen M, Akkina R, Anderson J, Villacres MC, Wu J, Zaia JA, Yee JK: Ex vivo selection and expansion of cells based on expression of a mutated inosine monophosphate dehydrogenase 2 after HIV vector transduction: effects on lymphocytes, monocytes, and CD34+ stem cells. Mol Ther. 2006 Aug;14(2):236-44. Epub 2006 May 2. [16647299 ]
  5. Dzidic A, Prgomet C, Mohr A, Meyer K, Bauer J, Meyer HH, Pfaffl MW: Effects of mycophenolic acid on inosine monophosphate dehydrogenase I and II mRNA expression in white blood cells and various tissues in sheep. J Vet Med A Physiol Pathol Clin Med. 2006 May;53(4):163-9. [16629948 ]
  6. Watkins WJ, Chen JM, Cho A, Chong L, Collins N, Fardis M, Huang W, Hung M, Kirschberg T, Lee WA, Liu X, Thomas W, Xu J, Zeynalzadegan A, Zhang J: Phosphonic acid-containing analogues of mycophenolic acid as inhibitors of IMPDH. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3479-83. Epub 2006 Apr 18. [16621550 ]
  7. Mitsuhashi S, Takenaka J, Iwamori K, Nakajima N, Ubukata M: Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase and differentiation induction of K562 cells among the mycophenolic acid derivatives. Bioorg Med Chem. 2010 Nov 15;18(22):8106-11. doi: 10.1016/j.bmc.2010.09.004. Epub 2010 Sep 18. [20934342 ]
  8. Dhar TG, Shen Z, Guo J, Liu C, Watterson SH, Gu HH, Pitts WJ, Fleener CA, Rouleau KA, Sherbina NZ, McIntyre KW, Shuster DJ, Witmer MR, Tredup JA, Chen BC, Zhao R, Bednarz MS, Cheney DL, MacMaster JF, Miller LM, Berry KK, Harper TW, Barrish JC, Hollenbaugh DL, Iwanowicz EJ: Discovery of N-[2-[2-[[3-methoxy-4-(5-oxazolyl)phenyl]amino]-5-oxazolyl]phenyl]-N-methyl-4- morpholineacetamide as a novel and potent inhibitor of inosine monophosphate dehydrogenase with excellent in vivo activity. J Med Chem. 2002 May 23;45(11):2127-30. [12014950 ]
  9. Watterson SH, Carlsen M, Dhar TG, Shen Z, Pitts WJ, Guo J, Gu HH, Norris D, Chorba J, Chen P, Cheney D, Witmer M, Fleener CA, Rouleau K, Townsend R, Hollenbaugh DL, Iwanowicz EJ: Novel inhibitors of IMPDH: a highly potent and selective quinolone-based series. Bioorg Med Chem Lett. 2003 Feb 10;13(3):543-6. [12565968 ]
  10. Dhar TG, Watterson SH, Chen P, Shen Z, Gu HH, Norris D, Carlsen M, Haslow KD, Pitts WJ, Guo J, Chorba J, Fleener CA, Rouleau KA, Townsend R, Hollenbaugh D, Iwanowicz EJ: Quinolone-based IMPDH inhibitors: introduction of basic residues on ring D and SAR of the corresponding mono, di and benzofused analogues. Bioorg Med Chem Lett. 2003 Feb 10;13(3):547-51. [12565969 ]
  11. Pitts WJ, Guo J, Dhar TG, Shen Z, Gu HH, Watterson SH, Bednarz MS, Chen BC, Barrish JC, Bassolino D, Cheney D, Fleener CA, Rouleau KA, Hollenbaugh DL, Iwanowicz EJ: Rapid synthesis of triazine inhibitors of inosine monophosphate dehydrogenase. Bioorg Med Chem Lett. 2002 Aug 19;12(16):2137-40. [12127522 ]
  12. Iwanowicz EJ, Watterson SH, Liu C, Gu HH, Mitt T, Leftheris K, Barrish JC, Fleener CA, Rouleau K, Sherbina NZ, Hollenbaugh DL: Novel guanidine-based inhibitors of inosine monophosphate dehydrogenase. Bioorg Med Chem Lett. 2002 Oct 21;12(20):2931-4. [12270177 ]
  13. Dhar TG, Liu C, Pitts WJ, Guo J, Watterson SH, Gu H, Fleener CA, Rouleau K, Sherbina NZ, Barrish JC, Hollenbaugh D, Iwanowicz EJ: A survey of cyclic replacements for the central diamide moiety of inhibitors of inosine monophosphate dehydrogenase. Bioorg Med Chem Lett. 2002 Nov 4;12(21):3125-8. [12372516 ]
  14. Dhar TG, Shen Z, Fleener CA, Rouleau KA, Barrish JC, Hollenbaugh DL, Iwanowicz EJ: The TosMIC approach to 3-(oxazol-5-yl) indoles: application to the synthesis of indole-based IMPDH inhibitors. Bioorg Med Chem Lett. 2002 Nov 18;12(22):3305-8. [12392738 ]
  15. Dhar TG, Shen Z, Gu HH, Chen P, Norris D, Watterson SH, Ballentine SK, Fleener CA, Rouleau KA, Barrish JC, Townsend R, Hollenbaugh DL, Iwanowicz EJ: 3-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships. Bioorg Med Chem Lett. 2003 Oct 20;13(20):3557-60. [14505670 ]
  16. Watterson SH, Chen P, Zhao Y, Gu HH, Dhar TG, Xiao Z, Ballentine SK, Shen Z, Fleener CA, Rouleau KA, Obermeier M, Yang Z, McIntyre KW, Shuster DJ, Witmer M, Dambach D, Chao S, Mathur A, Chen BC, Barrish JC, Robl JA, Townsend R, Iwanowicz EJ: Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419). J Med Chem. 2007 Jul 26;50(15):3730-42. Epub 2007 Jun 22. [17585753 ]
  17. Nelson PH, Carr SF, Devens BH, Eugui EM, Franco F, Gonzalez C, Hawley RC, Loughhead DG, Milan DJ, Papp E, Patterson JW, Rouhafza S, Sjogren EB, Smith DB, Stephenson RA, Talamas FX, Waltos AM, Weikert RJ, Wu JC: Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase by nuclear variants of mycophenolic acid. J Med Chem. 1996 Oct 11;39(21):4181-96. [8863796 ]
  18. Chen Z, Zheng Z, Huang H, Song Y, Zhang X, Ma J, Wang B, Zhang C, Ju J: Penicacids A-C, three new mycophenolic acid derivatives and immunosuppressive activities from the marine-derived fungus Penicillium sp. SOF07. Bioorg Med Chem Lett. 2012 May 1;22(9):3332-5. doi: 10.1016/j.bmcl.2012.02.106. Epub 2012 Mar 11. [22464133 ]
  19. Yang N, Wang QH, Wang WQ, Wang J, Li F, Tan SP, Cheng MS: The design, synthesis and in vitro immunosuppressive evaluation of novel isobenzofuran derivatives. Bioorg Med Chem Lett. 2012 Jan 1;22(1):53-6. doi: 10.1016/j.bmcl.2011.11.078. Epub 2011 Nov 28. [22172700 ]
  20. Lesiak K, Watanabe KA, Majumdar A, Powell J, Seidman M, Vanderveen K, Goldstein BM, Pankiewicz KW: Synthesis of a methylenebis(phosphonate) analogue of mycophenolic adenine dinucleotide: a glucuronidation-resistant MAD analogue of NAD. J Med Chem. 1998 Feb 12;41(4):618-22. [9484510 ]
  21. Chen L, Gao G, Felczak K, Bonnac L, Patterson SE, Wilson D, Bennett EM, Jayaram HN, Hedstrom L, Pankiewicz KW: Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analogues. J Med Chem. 2007 Nov 15;50(23):5743-51. Epub 2007 Oct 24. [17958343 ]
  22. Felczak K, Chen L, Wilson D, Williams J, Vince R, Petrelli R, Jayaram HN, Kusumanchi P, Kumar M, Pankiewicz KW: Cofactor-type inhibitors of inosine monophosphate dehydrogenase via modular approach: targeting the pyrophosphate binding sub-domain. Bioorg Med Chem. 2011 Mar 1;19(5):1594-605. doi: 10.1016/j.bmc.2011.01.042. Epub 2011 Jan 27. [21324702 ]
  23. Pankiewicz KW, Lesiak-Watanabe KB, Watanabe KA, Patterson SE, Jayaram HN, Yalowitz JA, Miller MD, Seidman M, Majumdar A, Prehna G, Goldstein BM: Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia. J Med Chem. 2002 Jan 31;45(3):703-12. [11806722 ]
  24. Chen L, Wilson D, Jayaram HN, Pankiewicz KW: Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment. J Med Chem. 2007 Dec 27;50(26):6685-91. Epub 2007 Nov 27. [18038969 ]
  25. Chen L, Petrelli R, Olesiak M, Wilson DJ, Labello NP, Pankiewicz KW: Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase. Bioorg Med Chem. 2008 Aug 1;16(15):7462-9. doi: 10.1016/j.bmc.2008.06.003. Epub 2008 Jun 10. [18583139 ]
  26. Chen L, Wilson DJ, Labello NP, Jayaram HN, Pankiewicz KW: Mycophenolic acid analogs with a modified metabolic profile. Bioorg Med Chem. 2008 Oct 15;16(20):9340-5. doi: 10.1016/j.bmc.2008.08.062. Epub 2008 Aug 29. [18809333 ]
General Function:
Rna binding
Specific Function:
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. 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.
Gene Name:
IMPDH1
Uniprot ID:
P20839
Molecular Weight:
55405.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.033 uMNot AvailableBindingDB 19264
Inhibitory0.04 uMNot AvailableBindingDB 19264
IC500.019 uMNot AvailableBindingDB 19264
IC500.02 uMNot AvailableBindingDB 19264
IC500.032 uMNot AvailableBindingDB 19264
IC500.055 uMNot AvailableBindingDB 19264
References
  1. Dzidic A, Prgomet C, Mohr A, Meyer K, Bauer J, Meyer HH, Pfaffl MW: Effects of mycophenolic acid on inosine monophosphate dehydrogenase I and II mRNA expression in white blood cells and various tissues in sheep. J Vet Med A Physiol Pathol Clin Med. 2006 May;53(4):163-9. [16629948 ]
  2. Mitsuhashi S, Takenaka J, Iwamori K, Nakajima N, Ubukata M: Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase and differentiation induction of K562 cells among the mycophenolic acid derivatives. Bioorg Med Chem. 2010 Nov 15;18(22):8106-11. doi: 10.1016/j.bmc.2010.09.004. Epub 2010 Sep 18. [20934342 ]
  3. Nelson PH, Eugui E, Wang CC, Allison AC: Synthesis and immunosuppressive activity of some side-chain variants of mycophenolic acid. J Med Chem. 1990 Feb;33(2):833-8. [1967654 ]
  4. Watkins WJ, Chen JM, Cho A, Chong L, Collins N, Fardis M, Huang W, Hung M, Kirschberg T, Lee WA, Liu X, Thomas W, Xu J, Zeynalzadegan A, Zhang J: Phosphonic acid-containing analogues of mycophenolic acid as inhibitors of IMPDH. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3479-83. Epub 2006 Apr 18. [16621550 ]
  5. Watterson SH, Carlsen M, Dhar TG, Shen Z, Pitts WJ, Guo J, Gu HH, Norris D, Chorba J, Chen P, Cheney D, Witmer M, Fleener CA, Rouleau K, Townsend R, Hollenbaugh DL, Iwanowicz EJ: Novel inhibitors of IMPDH: a highly potent and selective quinolone-based series. Bioorg Med Chem Lett. 2003 Feb 10;13(3):543-6. [12565968 ]
  6. Lesiak K, Watanabe KA, Majumdar A, Powell J, Seidman M, Vanderveen K, Goldstein BM, Pankiewicz KW: Synthesis of a methylenebis(phosphonate) analogue of mycophenolic adenine dinucleotide: a glucuronidation-resistant MAD analogue of NAD. J Med Chem. 1998 Feb 12;41(4):618-22. [9484510 ]
  7. Chen L, Gao G, Felczak K, Bonnac L, Patterson SE, Wilson D, Bennett EM, Jayaram HN, Hedstrom L, Pankiewicz KW: Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analogues. J Med Chem. 2007 Nov 15;50(23):5743-51. Epub 2007 Oct 24. [17958343 ]
  8. Felczak K, Chen L, Wilson D, Williams J, Vince R, Petrelli R, Jayaram HN, Kusumanchi P, Kumar M, Pankiewicz KW: Cofactor-type inhibitors of inosine monophosphate dehydrogenase via modular approach: targeting the pyrophosphate binding sub-domain. Bioorg Med Chem. 2011 Mar 1;19(5):1594-605. doi: 10.1016/j.bmc.2011.01.042. Epub 2011 Jan 27. [21324702 ]
  9. Pankiewicz KW, Lesiak-Watanabe KB, Watanabe KA, Patterson SE, Jayaram HN, Yalowitz JA, Miller MD, Seidman M, Majumdar A, Prehna G, Goldstein BM: Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia. J Med Chem. 2002 Jan 31;45(3):703-12. [11806722 ]
  10. Chen L, Wilson D, Jayaram HN, Pankiewicz KW: Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment. J Med Chem. 2007 Dec 27;50(26):6685-91. Epub 2007 Nov 27. [18038969 ]
  11. Chen L, Petrelli R, Olesiak M, Wilson DJ, Labello NP, Pankiewicz KW: Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase. Bioorg Med Chem. 2008 Aug 1;16(15):7462-9. doi: 10.1016/j.bmc.2008.06.003. Epub 2008 Jun 10. [18583139 ]
  12. Chen L, Wilson DJ, Labello NP, Jayaram HN, Pankiewicz KW: Mycophenolic acid analogs with a modified metabolic profile. Bioorg Med Chem. 2008 Oct 15;16(20):9340-5. doi: 10.1016/j.bmc.2008.08.062. Epub 2008 Aug 29. [18809333 ]
General Function:
Rna binding
Specific Function:
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. 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.
Gene Name:
IMPDH2
Uniprot ID:
P12268
Molecular Weight:
55804.495 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation110 uMNot AvailableBindingDB 19264
References
  1. Ubukata M, Takamori H, Ohashi M, Mitsuhashi S, Yamashita K, Asada T, Nakajima N, Matsuura N, Tsuruga M, Taki K, Magae J: Mycophenolic acid as a latent agonist of PPARgamma. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4767-70. Epub 2007 Jun 26. [17618115 ]
General Function:
Rna binding
Specific Function:
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. 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.
Gene Name:
IMPDH2
Uniprot ID:
P12268
Molecular Weight:
55804.495 Da