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Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:30:12 UTC
HMDB IDHMDB14826
Secondary Accession NumbersNone
Metabolite Identification
Common NameMycophenolate mofetil
DescriptionMycophenolate mofetil is only found in individuals that have used or taken this drug. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent, inosine monophosphate dehydrogenase (IMPDH) inhibitor.Mycophenolate mofetil is hydrolyzed to form mycophenolic acid (MPA), which is the active metabolite. MPA 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, MPA has potent cytostatic effects on lymphocytes. MPA inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of MPA on lymphocytes. MPA also suppresses antibody formation by B-lymphocytes. MPA 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. Mycophenolate mofetil did not inhibit early events in the activation of human peripheral blood mononuclear cells, such as the production of interleukin-1 (IL-1) and interleukin-2 (IL-2), but did block the coupling of these events to DNA synthesis and proliferation.
Structure
Thumb
Synonyms
ValueSource
2-Morpholinoethyl (e)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoateChEBI
CellceptChEBI
MMFChEBI
Mycophenolic acid morpholinoethyl esterChEBI
RS 61443ChEBI
2-Morpholinoethyl (e)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acidGenerator
Mycophenolic acid mofetilGenerator
Mycophenolate morpholinoethyl esterGenerator
Mycophenylate mofetilHMDB
Chemical FormulaC23H31NO7
Average Molecular Weight433.4947
Monoisotopic Molecular Weight433.210052351
IUPAC Name2-(morpholin-4-yl)ethyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
Traditional Namemycophenolate mofetil
CAS Registry Number128794-94-5
SMILES
COC1=C(C\C=C(/C)CCC(=O)OCCN2CCOCC2)C(O)=C2C(=O)OCC2=C1C
InChI Identifier
InChI=1S/C23H31NO7/c1-15(5-7-19(25)30-13-10-24-8-11-29-12-9-24)4-6-17-21(26)20-18(14-31-23(20)27)16(2)22(17)28-3/h4,26H,5-14H2,1-3H3/b15-4+
InChI KeyInChIKey=RTGDFNSFWBGLEC-SYZQJQIISA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phthalides. These are compounds containing a 3-hydrocarbylidene-2-benzofuran-1(3H)-one moiety,.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsobenzofurans
Sub ClassIsobenzofuranones
Direct ParentPhthalides
Alternative Parents
Substituents
  • Phthalide
  • Methoxyphenol
  • Anisole
  • Fatty acid ester
  • Alkyl aryl ether
  • Fatty acyl
  • Benzenoid
  • Oxazinane
  • Morpholine
  • Dicarboxylic acid or derivatives
  • Vinylogous acid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactone
  • Carboxylic acid ester
  • Oxacycle
  • Azacycle
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antineoplastic Agents
  • Dermatologic Agents
  • Enzyme Inhibitors
  • Immunosuppressive Agents
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility9.50e-02 g/LNot Available
LogP2.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.095 mg/mLALOGPS
logP2.17ALOGPS
logP3.47ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)9.76ChemAxon
pKa (Strongest Basic)6.19ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area94.53 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity117.1 m3·mol-1ChemAxon
Polarizability45.55 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Mycophenolic Acid Metabolism PathwaySMP00652Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00688
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00688
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00688
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4444535
KEGG Compound IDC07908
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMycophenolate_mofetil
NuGOwiki LinkHMDB14826
Metagene LinkHMDB14826
METLIN IDNot Available
PubChem Compound5281078
PDB IDNot Available
ChEBI ID8764
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Picard N, Cresteil T, Premaud A, Marquet P: Characterization of a phase 1 metabolite of mycophenolic acid produced by CYP3A4/5. Ther Drug Monit. 2004 Dec;26(6):600-8. [15570183 ]
  2. 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 ]
  3. FDA label

Enzymes

General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular weight:
60720.15
References
  1. Picard N, Ratanasavanh D, Premaud A, Le Meur Y, Marquet P: Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos. 2005 Jan;33(1):139-46. Epub 2004 Oct 6. [15470161 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular weight:
59590.91
References
  1. Miles KK, Kessler FK, Smith PC, Ritter JK: Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9. Epub 2006 Jun 21. [16790558 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular weight:
59940.495
References
  1. Picard N, Ratanasavanh D, Premaud A, Le Meur Y, Marquet P: Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos. 2005 Jan;33(1):139-46. Epub 2004 Oct 6. [15470161 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A8
Uniprot ID:
Q9HAW9
Molecular weight:
59741.035
References
  1. Thervet E, Anglicheau D, Legendre C: [Pharmacology of mycophenolate mofetil: recent data and clinical consequences]. Nephrologie. 2001;22(7):331-7. [11817210 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A10
Uniprot ID:
Q9HAW8
Molecular weight:
59809.075
References
  1. Thervet E, Anglicheau D, Legendre C: [Pharmacology of mycophenolate mofetil: recent data and clinical consequences]. Nephrologie. 2001;22(7):331-7. [11817210 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A6
Uniprot ID:
P19224
Molecular weight:
60750.215
References
  1. Miles KK, Kessler FK, Smith PC, Ritter JK: Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9. Epub 2006 Jun 21. [16790558 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A7
Uniprot ID:
Q9HAW7
Molecular weight:
59818.315
References
  1. Miles KK, Kessler FK, Smith PC, Ritter JK: Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9. Epub 2006 Jun 21. [16790558 ]
General function:
Involved in catalytic activity
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
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. Bremer S, Rootwelt H, Bergan S: Real-time PCR determination of IMPDH1 and IMPDH2 expression in blood cells. Clin Chem. 2007 Jun;53(6):1023-9. Epub 2007 Apr 26. [17463174 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General function:
Involved in catalytic activity
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:
63252.24
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Bremer S, Rootwelt H, Bergan S: Real-time PCR determination of IMPDH1 and IMPDH2 expression in blood cells. Clin Chem. 2007 Jun;53(6):1023-9. Epub 2007 Apr 26. [17463174 ]
  4. Wang J, Yang JW, Zeevi A, Webber SA, Girnita DM, Selby R, Fu J, Shah T, Pravica V, Hutchinson IV, Burckart GJ: IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients. Clin Pharmacol Ther. 2008 May;83(5):711-7. Epub 2007 Sep 12. [17851563 ]
  5. Sanquer S, Maison P, Tomkiewicz C, Macquin-Mavier I, Legendre C, Barouki R, Lang P: Expression of inosine monophosphate dehydrogenase type I and type II after mycophenolate mofetil treatment: a 2-year follow-up in kidney transplantation. Clin Pharmacol Ther. 2008 Feb;83(2):328-35. Epub 2007 Aug 22. [17713475 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]