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Identification
Name Mycophenolic acid
Accession Number DB01024 (APRD01603, EXPT02208)
Type small molecule
Groups approved
Description

Mycophenolic 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).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Mycophenoic acid
Salts Not Available
Brand names
Name Company
Melbex
Myfortic
Brand mixtures Not Available
Categories
  • Enzyme Inhibitors
  • Antibiotics, Antineoplastic
CAS number 24280-93-1
Weight Average: 320.3371
Monoisotopic: 320.125988372
Chemical Formula C17H20O6
InChI Key InChIKey=HPNSFSBZBAHARI-RUDMXATFSA-N
InChI
InChI=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+
Plain Text
IUPAC Name
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
SMILES
COC1=C(C\C=C(/C)CCC(O)=O)C(O)=C2C(=O)OCC2=C1C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Salicylates and Derivatives
  • Benzene and Derivatives
  • Benzyl Esters
  • Benzylacetates
  • Methoxyphenols
Substructures
  • Carboxylic Acids and Derivatives
  • Benzofurans
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Salicylates and Derivatives
  • Phenols and Derivatives
  • Lactones
  • Ethers
  • Benzene and Derivatives
  • Benzyl Esters
  • Benzylacetates
  • Methoxyphenols
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Benzoyl Derivatives
  • Phenyl Esters
Pharmacology
Indication For the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.
Pharmacodynamics Mycophenolic acid is an antibiotic substance derived from Penicillium stoloniferum. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites.
Mechanism of action Mycophenolic 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.
Absorption Bioavailability following oral administration of Myfortic delayed-release tablet ranges from 70-95%
Volume of distribution
  • 54 ± 25 L
Protein binding >98%
Metabolism Mycophenolic 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.
Route of elimination Not Available
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.
Clearance
  • 140 +/- 30 mL/min [Stable renal transplant patients]
Toxicity Oral (LD50): Acute: 352 mg/kg [Rat], 1000 mg/kg [Mouse], and >6000 mg/kg [Rabbit]. Possible 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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Tablet, coated Oral
Prices
Unit description Cost Unit
Myfortic 360 mg Enteric Coated Tabs 8.0 USD tab
Myfortic 360 mg tablet 7.69 USD tablet
Myfortic 180 mg tablet 3.85 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6025391 1997-04-10 2017-04-10
Canada 2250906 2006-10-03 2017-04-10
Properties
State solid
Experimental Properties
Property Value Source
melting point 141 °C PhysProp
water solubility Insoluble Not Available
logP 2.8 Not Available
Predicted Properties
Property Value Source
water solubility 3.55e-02 g/l ALOGPS
logP 2.36 ALOGPS
logP 3.53 ChemAxon
logS -4 ALOGPS
pKa (strongest acidic) 3.57 ChemAxon
pKa (strongest basic) -4.1 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 93.06 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 85.23 ChemAxon
polarizability 32.95 ChemAxon
References
Synthesis Reference Not Available
General Reference
  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. Pubmed
External Links
Resource Link
PubChem Compound 446541 Link_out
PubChem Substance 46504559 Link_out
ChemSpider 393865 Link_out
BindingDB 19264 Link_out
ChEBI 168396 Link_out
ChEMBL 168396 Link_out
Therapeutic Targets Database DAP000784 Link_out
PharmGKB PA164748728 Link_out
HET MOA Link_out
Drug Product Database 2264560 Link_out
Drugs.com http://www.drugs.com/cdi/mycophenolic-acid-delayed-release-tablets.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mycophenolic_acid Link_out
ATC Codes
  • L04AA06
AHFS Codes
  • 92:00.00
PDB Entries
FDA label Not Available
MSDS show (74 KB)
Interactions
Drug Interactions
Drug Interaction
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Valganciclovir The excretion rates of Valganciclovir and/or Mycophenolic acid may decrease. Monitor for increased serum concentrations and toxicity of both agents.
Food Interactions Not Available
Targets

1. Inosine-5'-monophosphate dehydrogenase 1

Pharmacological action: yes
Actions: inhibitor

Rate limiting enzyme in the de novo synthesis of guanine nucleotides and therefore is involved in the regulation of cell growth. It may also have a role in the development of malignancy and the growth progression of some tumors

Organism class: human
UniProt ID: P20839 Link_out
Gene: IMPDH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed

2. Inosine-5'-monophosphate dehydrogenase 2

Pharmacological action: yes
Actions: inhibitor

Rate limiting enzyme in the de novo synthesis of guanine nucleotides and therefore is involved in the regulation of cell growth. It may also have a role in the development of malignancy and the growth progression of some tumors

Organism class: human
UniProt ID: P12268 Link_out
Gene: IMPDH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. UDP-glucuronosyltransferase 1-1

Actions: substrate

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

UniProt ID: P22309 Link_out
Gene: UGT1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dostalek M, Court MH, Hazarika S, Akhlaghi F: Diabetes mellitus reduces activity of human UDP-glucuronosyltransferase 2B7 in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite. Drug Metab Dispos. 2011 Mar;39(3):448-55. Epub 2010 Dec 1. Pubmed
  2. 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. Pubmed

2. UDP-glucuronosyltransferase 1-9

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols

UniProt ID: O60656 Link_out
Gene: UGT1A9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dostalek M, Court MH, Hazarika S, Akhlaghi F: Diabetes mellitus reduces activity of human UDP-glucuronosyltransferase 2B7 in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite. Drug Metab Dispos. 2011 Mar;39(3):448-55. Epub 2010 Dec 1. Pubmed
  2. 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. Pubmed

3. UDP-glucuronosyltransferase 2B7

Actions: substrate

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

UniProt ID: P16662 Link_out
Gene: UGT2B7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dostalek M, Court MH, Hazarika S, Akhlaghi F: Diabetes mellitus reduces activity of human UDP-glucuronosyltransferase 2B7 in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite. Drug Metab Dispos. 2011 Mar;39(3):448-55. Epub 2010 Dec 1. Pubmed
  2. 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. Pubmed

4. UDP-glucuronosyltransferase 1-7

Actions: substrate
UniProt ID: Q9HAW7 Link_out

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. Pubmed

5. UDP-glucuronosyltransferase 1-6

Actions: substrate
UniProt ID: P19224 Link_out

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. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19