Mycophenolic acid

Identification

Summary

Mycophenolic acid is an immunosuppressant used to prevent organ transplant rejections.

Brand Names
Myfortic
Generic Name
Mycophenolic acid
DrugBank Accession Number
DB01024
Background

Mycophenolic acid is a potent immunosuppressant agent that inhibits de novo purine biosynthesis.7 It was derived from Penicillium stoloniferum, and has also shown antibacterial, antifungal and antiviral properties.1. Mycophenolic acid is used in immunosuppressive regimens as part of a triple therapy that includes a calcineurin inhibitor (ciclosporin or tacrolimus) and prednisolone.2 This regimen can be used in place of the older anti-proliferative azathioprine due to its stronger immunosuppressive potency.3 However, mycophenolic acid treatment is more expensive and requires therapeutic drug monitoring to optimize efficacy and minimize toxicity.3,4 Mycophenolic acid is available as enteric-coated tablets of delayed-release, in an effort to improve upper gastrointestinal adverse events by delaying mycophenolic acid release until it reaches the small intestine.5 Mycophenolate mofetil, a prodrug of mycophenolic acid, is also prescribed to transplant recipients to prevent organ rejection.8

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 320.3371
Monoisotopic: 320.125988372
Chemical Formula
C17H20O6
Synonyms
  • (e)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid
  • Acide mycophenolique
  • Acido micofenolico
  • Acidum mycophenolicum
  • Micofenolico acido
  • Mycophenolate
  • Mycophenolic acid
  • Mycophenolsäure
External IDs
  • 68618
  • NSC-129185

Pharmacology

Indication

Mycophenolic acid is an antimetabolite immunosuppressant indicated for prophylaxis of organ rejection in adult patients receiving kidney transplants and in pediatric patients at least 5 years of age and older who are at least 6 months post kidney transplant. Mycophenolic acid is used in combination with cyclosporine and corticosteroids.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used as adjunct in combination to preventKidney transplant rejectionRegimen in combination with: Cyclosporine (DB00091)•••••••••••••••••••••••••••• ••••••• •••••••
Used as adjunct in combination to preventKidney transplant rejectionRegimen in combination with: Cyclosporine (DB00091)•••••••••••••••••••••••• ••••••• •••••••
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Pharmacodynamics

Mycophenolic acid is a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH) that blocks de novo biosynthesis of purine nucleotides. This affects lymphocytes primarily and leads to the suppression of DNA synthesis in T- and B-cells.2,7 Mycophenolic acid arrests the T-lymphocyte cell cycle at the G1/S interface and inhibits the proliferation of lymphocytes.2 Also, it has been suggested that mycophenolic acid suppresses cytokine production by limiting the number of cytokine-producing cells.2 The enteric-coating of mycophenolic acid tablets prevents the development of upper gastrointestinal adverse events by delaying drug release until it reaches the small intestine.5

Patients treated with mycophenolic acid have a higher risk of developing new or reactivated viral infections, serious infections, blood dyscrasias (including pure red cell aplasia), serious gastrointestinal tract complications, acute inflammatory syndrome associated with mycophenolate products, lymphoma, and other malignancies.7 The use of mycophenolic acid is also associated with an increased risk of first-trimester pregnancy loss and congenital malformations. Mycophenolic acid should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). Patients treated with mycophenolic acid should not receive live attenuated vaccines or donate blood or semen.7

Mechanism of action

Mycophenolic acid is a selective noncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), that blocks the conversion of inosine-5-phosphate and xanthine-5-phosphate to guanosine-5-phosphate.1,7 By inhibiting IMPDH, mycophenolic acid interferes with the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. While other cell types are able to use salvage pathways, T- and B-lymphocyte proliferation is a mechanism heavily dependent on the de novo synthesis of purines. Therefore, mycophenolic acid has potent cytostatic effects on T- and B- and lymphocytes.1,7 Mycophenolic acid also suppresses antibody formation by B-lymphocytes and prevents the glycosylation of lymphocyte and monocyte glycoproteins involved in intercellular adhesion to endothelial cells.8

TargetActionsOrganism
AInosine-5'-monophosphate dehydrogenase 2
inhibitor
Humans
AInosine-5'-monophosphate dehydrogenase 1
inhibitor
Humans
Absorption

Between 360 mg and 2,160 mg, mycophenolic acid follows a linear and dose-proportional pharmacokinetic profile. The enteric-coating of mycophenolic acid tablets prevents release under acidic conditions (stomach, pH < 5). However, enteric-coated mycophenolic acid tablets are highly soluble in neutral pH conditions such as those in the intestine.7 In renal transplant patients, the median delay (Tlag) in the rise of mycophenolic acid concentration ranged between 0.25 and 1.25 hours, and the Tmax ranged between 1.5 and 2.75 hours. Adult renal transplant patients on cyclosporine given mycophenolic acid had a Tmax of 2 h, a Cmax of 26.1 μg/mL, and an AUC0-12 of 66.5 μg⋅h/mL. Stable pediatric (5-16 years old) renal transplant patients had a Cmax and AUC 33% and 18% higher than the ones detected in adults.7

In stable renal transplant patients treated with cyclosporine, the gastrointestinal absorption and absolute bioavailability of delayed-release tablets of mycophenolic acid were 93% and 72%, respectively.7 Following the administration of a high-fat meal (55 g fat, 1000 calories), the AUC of mycophenolic acid (enteric-coated tablets, 720 mg) was comparable to the one detected during fasting. However, a high-fat meal can lead to a 33% decrease of the Cmax, a 3.5-hour delay in the Tlag (range of -6 to 18 hours), and a 5.0-hour delay in the Tmax (range of -9 to 20 hours). To avoid variability in the absorption of mycophenolic acid, this drug should be taken on an empty stomach.7

Volume of distribution

At steady state, the volume of distribution of mycophenolic acid is 54 L. At the elimination phase, the volume of distribution of mycophenolic acid is 112 L.7

Protein binding

Mycophenolic acid is highly protein-bound, and more than 98% of it is bound to albumin.7

Metabolism

Mycophenolic acid is mainly metabolized by glucuronyl transferase to form glucuronidated metabolites. Mycophenolic acid glucuronide (MPAG), the major metabolite of mycophenolic acid, does not display pharmacological activity. However, the acyl glucuronide minor metabolite has a pharmacological activity similar to mycophenolic acid. The AUC ratio of mycophenolic acid:MPAG:acyl glucuronide is approximately 1:24:0.28 at a steady state.7

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Route of elimination

In stable renal transplant patients, approximately 60% of mycophenolic acid is eliminated in the urine as mycophenolic acid glucuronide (MPAG), while 3% is eliminated unchanged.7 MPAG is also secreted in the bile and is available for deconjugation by gut flora. The mycophenolic acid that results from MPAG deconjugation may be reabsorbed and produce a second peak 6-8 hours after administration.7

Half-life

The mean elimination half-life of mycophenolic acid ranges between 8 and 16 hours, while the mean elimination half-life of mycophenolic acid glucuronide, its major metabolite, ranges between 13 and 17 hours.7

Clearance

The mean clearance of mycophenolic acid is 140 mL/min. The mean renal clearance of its metabolite, mycophenolic acid glucuronide, is 15.5 mL/min.7

Adverse Effects
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Toxicity

There are anecdotal reports of deliberate or accidental overdoses with mycophenolic acid; however, not all patients have experienced related adverse reactions. In those cases where adverse reactions have been reported, reactions fall within the safety profile of its class of drugs. A mycophenolic acid overdose could lead to the oversuppression of the immune system and increase the susceptibility to infection.7 It may be appropriate to interrupt or discontinue mycophenolic acid if blood dyscrasias occur. Some of the signs and symptoms associated with mycophenolic acid overdose are hematological abnormalities, such as leukopenia and neutropenia, and gastrointestinal symptoms, such as abdominal pain, diarrhea, nausea and vomiting, and dyspepsia.7

Carcinogenicity studies of 104 weeks done in rats and mice, suggest that mycophenolate sodium does not induce the formation of tumours. Rats were given up to 9 mg/kg of mycophenolate sodium, which corresponded to 0.6-1.2 times the systemic exposure observed in renal transplant patients, while mice were given 180 mg/kg, an equivalent of 0.6 times the mycophenolate sodium therapeutic dose.7 The genotoxicity of mycophenolate sodium was confirmed by the mouse lymphoma/thymidine kinase assay, the micronucleus test in V79 Chinese hamster cells, and the in vivo mouse micronucleus assay. Mycophenolate mofetil, a prodrug of mycophenolic acid, had a similar genotoxic profile. At daily oral doses as high as 18 mg/kg and 20 mg/kg, mycophenolate sodium had no effect on male and female rat fertility, respectively.7 The oral LD50 of mycophenolic acid is 352 mg/kg in rats and 1000 mg/kg in mice.9

Pathways
PathwayCategory
Mycophenolic Acid Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMycophenolic acid may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Abatacept.
AceclofenacAceclofenac may decrease the excretion rate of Mycophenolic acid which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Mycophenolic acid which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Mycophenolic acid is combined with Acenocoumarol.
Food Interactions
  • Take on an empty stomach. Take mycophenolic acid at least 1 hour before or 2 hours after eating.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Mycophenolate sodiumWX877SQI1G37415-62-6DOZYTHNHLLSNIK-JOKMOOFLSA-M
Product Images
International/Other Brands
Melbex / Myfortic (Novartis Pharmaceuticals Corporation)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Mycophenolic AcidTablet, delayed release180 mgOralJamp Pharma Corporation2021-11-10Not applicableCanada flag
Mycophenolic AcidTablet, delayed release360 mgOralJamp Pharma Corporation2021-11-10Not applicableCanada flag
MyforticTablet, delayed release360 mgOralNovartis2005-02-11Not applicableCanada flag
MyforticTablet, delayed release180 mg/1OralNovartis Pharmaceuticals Corporation2004-02-27Not applicableUS flag
MyforticTablet, delayed release180 mgOralNovartis2005-02-11Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-mycophenolic AcidTablet, delayed release360 mgOralApotex Corporation2014-07-02Not applicableCanada flag
Apo-mycophenolic AcidTablet, delayed release180 mgOralApotex Corporation2014-07-02Not applicableCanada flag
Mar-mycophenolic AcidTablet, delayed release360 mgOralMarcan Pharmaceuticals Inc2021-04-07Not applicableCanada flag
Mar-mycophenolic AcidTablet, delayed release180 mgOralMarcan Pharmaceuticals Inc2021-04-07Not applicableCanada flag
Mycophenolic AcidTablet, delayed release360 mg/1OralCONCORD BIOTECH LIMITED2019-12-13Not applicableUS flag

Categories

ATC Codes
L04AA06 — Mycophenolic acid
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phthalides. These are compounds containing a 3-hydrocarbylidene-2-benzofuran-1(3H)-one moiety,.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isocoumarans
Sub Class
Isobenzofuranones
Direct Parent
Phthalides
Alternative Parents
Anisoles / Medium-chain fatty acids / Alkyl aryl ethers / Methyl-branched fatty acids / Hydroxy fatty acids / Heterocyclic fatty acids / Unsaturated fatty acids / Dicarboxylic acids and derivatives / Vinylogous acids / Lactones
show 6 more
Substituents
Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Benzenoid / Branched fatty acid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Carboxylic acid ester / Dicarboxylic acid or derivatives
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
2-benzofurans, monocarboxylic acid, phenols, gamma-lactone (CHEBI:168396)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
HU9DX48N0T
CAS number
24280-93-1
InChI Key
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+
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

References

Synthesis Reference

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

US4234684
General References
  1. Kitchin JE, Pomeranz MK, Pak G, Washenik K, Shupack JL: Rediscovering mycophenolic acid: a review of its mechanism, side effects, and potential uses. J Am Acad Dermatol. 1997 Sep;37(3 Pt 1):445-9. doi: 10.1016/s0190-9622(97)70147-6. [Article]
  2. Shaw LM, Korecka M, Venkataramanan R, Goldberg L, Bloom R, Brayman KL: Mycophenolic acid pharmacodynamics and pharmacokinetics provide a basis for rational monitoring strategies. Am J Transplant. 2003 May;3(5):534-42. doi: 10.1034/j.1600-6143.2003.00079.x. [Article]
  3. Wagner M, Earley AK, Webster AC, Schmid CH, Balk EM, Uhlig K: Mycophenolic acid versus azathioprine as primary immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev. 2015 Dec 3;(12):CD007746. doi: 10.1002/14651858.CD007746.pub2. [Article]
  4. Kiang TKL, Ensom MHH: Exposure-Toxicity Relationships of Mycophenolic Acid in Adult Kidney Transplant Patients. Clin Pharmacokinet. 2019 Dec;58(12):1533-1552. doi: 10.1007/s40262-019-00802-z. [Article]
  5. Budde K, Glander P, Diekmann F, Waiser J, Fritsche L, Dragun D, Neumayer HH: Review of the immunosuppressant enteric-coated mycophenolate sodium. Expert Opin Pharmacother. 2004 Jun;5(6):1333-45. doi: 10.1517/14656566.5.6.1333. [Article]
  6. FDA Approved Drug Products: Myfortic (mycophenolic acid) delayed-release tablets for oral use [Link]
  7. FDA Approved Drug Products: MYFORTIC (mycophenolic acid) delayed-release tablets for oral use [Link]
  8. FDA Approved Drug Products: Cellcept (mycophenolate mofetil) for oral or intravenous administration [Link]
  9. Santa Cruz Biotechnology: Mycophenolic acid SDS [Link]
Human Metabolome Database
HMDB0015159
PubChem Compound
446541
PubChem Substance
46504559
ChemSpider
393865
BindingDB
19264
RxNav
265323
ChEBI
168396
ChEMBL
CHEMBL866
ZINC
ZINC000000001758
Therapeutic Targets Database
DAP000784
PharmGKB
PA164748728
PDBe Ligand
MOA
Drugs.com
Drugs.com Drug Page
Wikipedia
Mycophenolic_acid
PDB Entries
1jr1 / 1me7 / 1meh / 1mei / 4af0 / 4fo4 / 4fxs / 7dbl / 7wkz
MSDS
Download (74 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentHepatocellular Carcinoma1
4CompletedDiagnosticImmunosuppression / Kidney Transplant Rejection1
4CompletedPreventionAnesthetics Adverse Reaction / Kidney Transplantation1
4CompletedPreventionCytomegalovirus (CMV) Infections / Transplantation Infection1
4CompletedPreventionDe Novo Kidney Transplantation2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Novartis AG
Dosage Forms
FormRouteStrength
Tablet, delayed releaseOral180 mg
Tablet, delayed releaseOral360 mg
Tablet, film coatedOral500 MG
Capsule, coatedOral25000000 mg
Injection, powder, lyophilized, for solutionParenteral500 mg
SuspensionOral20 g
TabletOral500.00 mg
Tablet, coatedOral250 mg
Tablet, coatedOral500 mg
Capsule, coatedOral250 mg
Tablet, film coatedOral250 MG
CapsuleOral250 mg
Tablet, coatedOral50000000 mg
Tablet, delayed releaseOral180 mg/1
Tablet, delayed releaseOral360 mg/1
TabletOral180 mg
TabletOral360 mg
TabletOral180.000 mg
Tablet, delayed releaseOral
Tablet, delayed releaseOral192.4 MG
Tablet, delayed releaseOral384.8 MG
Tablet, film coatedOral180 mg
Tablet, film coatedOral360 mg
Tablet, film coatedOral
Tablet, coatedOral180 mg
TabletOral500 mg
Prices
Unit descriptionCostUnit
Myfortic 360 mg Enteric Coated Tabs8.0USD tab
Myfortic 360 mg tablet7.69USD tablet
Myfortic 180 mg tablet3.85USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2250906No2006-10-032017-04-10Canada flag
US6025391No2000-02-152017-04-10US flag
US6172107No2001-01-092017-04-10US flag
US6306900No2001-10-232018-02-27US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)141°CPhysProp
water solubilityInsolubleNot Available
logP2.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0355 mg/mLALOGPS
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 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity85.23 m3·mol-1Chemaxon
Polarizability32.95 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9409
Blood Brain Barrier+0.5826
Caco-2 permeable-0.5583
P-glycoprotein substrateSubstrate0.8058
P-glycoprotein inhibitor INon-inhibitor0.7888
P-glycoprotein inhibitor IIInhibitor0.545
Renal organic cation transporterNon-inhibitor0.8199
CYP450 2C9 substrateNon-substrate0.8305
CYP450 2D6 substrateNon-substrate0.8575
CYP450 3A4 substrateSubstrate0.6934
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7237
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9619
BiodegradationReady biodegradable0.5888
Rat acute toxicity2.9907 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.753
hERG inhibition (predictor II)Non-inhibitor0.6329
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0bvm-0091000000-bb41ce2ccd5996f6c67c
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0udi-0019000000-01d925bb1f9079308d85
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0a4i-0091000000-22fc916594dbab851293
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0a4i-0940000000-84f4c65c2cd8b7358b78
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0a4i-0593000000-1fed07ad435ca0bd7249
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0udi-0249000000-bd1d2df9c9ae8a17841f
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-002r-0490000000-99420edc8894323b59c3
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0009000000-b99d88ff2ddeb6977c4a
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0149000000-ed6b854b4f9af495c8d8
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0972000000-12d0e80f109d1fa6eb11
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0950000000-2e6c3543fe3f9f4e0790
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0930000000-e7a74fbe76e7141ec5f3
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-022c-0910000000-27f7c0023a8b7e5b4d66
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0009000000-4aba5ee4ba77899b36fb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0149000000-497b49ab395f3319c943
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0971000000-68634f04b665bb0e68a3
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0950000000-37f2ee0320d2ec560b93
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0f6x-0930000000-500359a3fd82c686ff99
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-006x-0900000000-6d04c3395aae26f88529
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-002r-0590000000-fe2f27357ba775714c5a
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0009000000-8f75c9bc48b5eb019974
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0009000000-57a06531623d00c32d13
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-002r-0490000000-700501110e03f998e99b
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-002r-0490000000-d857a6e047fc52e09e65
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-0659000000-ba96d820001d9e786c8d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-8855932a0a5c9af1f1f6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-5eab5855829b8f8b0eea
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0pb9-0093000000-19fd59af4878ea5f1a97
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0190000000-6f584505d9b70bbffa5e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0890000000-fb7dec2fc3d23163125f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-1910000000-107f1e78387f32f7de88
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0pbc-3900000000-b1724166cac37a86cf14
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-8de82df3dfe7724905cc
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0pb9-0093000000-921ff4437b7ebfa1c724
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0190000000-51bdcbf497148c8b5520
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0890000000-c295a83b84c00d94f85f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-1910000000-92e91c6ef0f2c538121f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0pbc-3900000000-410eebeb0513756f40b0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-77bcd201c9d0349c0389
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0900000000-da3123e3ecb85f0d28ff
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0900000000-90103d288430929083b5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0090000000-3f6f29caf26c0469c12c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0090000000-7fc1bdce2eebcc00617c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0019000000-01d925bb1f9079308d85
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0091000000-22fc916594dbab851293
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0940000000-84f4c65c2cd8b7358b78
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0593000000-1fed07ad435ca0bd7249
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0950000000-87024d6b180d1fc1c64f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0493000000-9b99fb030e87f52cce17
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0294000000-31d6abb5cfcd65770f2c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zfr-0089000000-66609d054e3d113a639f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-016r-0098000000-667df4a7f8292b9099e4
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0091000000-113d8b5c8aa105575e96
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0adi-0090000000-244525829ea65de36003
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0aor-0290000000-57474a6f9f5b72f1d757
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0159-0190000000-14d45f13a3fa259b926a
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zfr-0089000000-66609d054e3d113a639f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-016r-0098000000-667df4a7f8292b9099e4
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0adi-0090000000-244525829ea65de36003
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0091000000-113d8b5c8aa105575e96
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0aor-0290000000-57474a6f9f5b72f1d757
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0159-0190000000-14d45f13a3fa259b926a
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-188.3060478
predicted
DarkChem Lite v0.1.0
[M-H]-188.3875478
predicted
DarkChem Lite v0.1.0
[M-H]-193.3456478
predicted
DarkChem Lite v0.1.0
[M-H]-174.08586
predicted
DeepCCS 1.0 (2019)
[M-H]-188.3060478
predicted
DarkChem Lite v0.1.0
[M-H]-188.3875478
predicted
DarkChem Lite v0.1.0
[M-H]-193.3456478
predicted
DarkChem Lite v0.1.0
[M-H]-174.08586
predicted
DeepCCS 1.0 (2019)
[M+H]+187.1719478
predicted
DarkChem Lite v0.1.0
[M+H]+188.4285478
predicted
DarkChem Lite v0.1.0
[M+H]+190.6414478
predicted
DarkChem Lite v0.1.0
[M+H]+176.44386
predicted
DeepCCS 1.0 (2019)
[M+H]+187.1719478
predicted
DarkChem Lite v0.1.0
[M+H]+188.4285478
predicted
DarkChem Lite v0.1.0
[M+H]+190.6414478
predicted
DarkChem Lite v0.1.0
[M+H]+176.44386
predicted
DeepCCS 1.0 (2019)
[M+Na]+188.0479478
predicted
DarkChem Lite v0.1.0
[M+Na]+188.5075478
predicted
DarkChem Lite v0.1.0
[M+Na]+191.1732478
predicted
DarkChem Lite v0.1.0
[M+Na]+184.06657
predicted
DeepCCS 1.0 (2019)
[M+Na]+188.0479478
predicted
DarkChem Lite v0.1.0
[M+Na]+188.5075478
predicted
DarkChem Lite v0.1.0
[M+Na]+191.1732478
predicted
DarkChem Lite v0.1.0
[M+Na]+184.06657
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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 pl...
Gene Name
IMPDH2
Uniprot ID
P12268
Uniprot Name
Inosine-5'-monophosphate dehydrogenase 2
Molecular Weight
55804.495 Da
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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 pl...
Gene Name
IMPDH1
Uniprot ID
P20839
Uniprot Name
Inosine-5'-monophosphate dehydrogenase 1
Molecular Weight
55405.365 Da
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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
The acyl glucuronide metabolite of mycophenolic acid is mainly generated by UGT2B7.
General Function
Glucuronosyltransferase activity
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 su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
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. doi: 10.1124/dmd.110.036608. Epub 2010 Dec 1. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
UGT1A8 is the main extra-hepatic enzyme involved in the formation of the mycophenolic acid-7-O-glucuronide metabolite.
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A8
Uniprot ID
Q9HAW9
Uniprot Name
UDP-glucuronosyltransferase 1-8
Molecular Weight
59741.035 Da
References
  1. Bernard O, Guillemette C: The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab Dispos. 2004 Aug;32(8):775-8. doi: 10.1124/dmd.32.8.775. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
UGT1A9 is the main hepatic enzyme involved in the formation of the mycophenolic acid-7-O-glucuronide metabolite.
General Function
Retinoic acid binding
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. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
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. doi: 10.1124/dmd.110.036608. Epub 2010 Dec 1. [Article]
  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. [Article]
  3. Bernard O, Guillemette C: The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab Dispos. 2004 Aug;32(8):775-8. doi: 10.1124/dmd.32.8.775. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
UGT1A1, UGT1A7, and UGT1A10 play a minor role in the formation of mycophenolic acid-7-O-glucuronide.
General Function
Steroid binding
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...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
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. doi: 10.1124/dmd.110.036608. Epub 2010 Dec 1. [Article]
  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. [Article]
  3. Bernard O, Guillemette C: The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab Dispos. 2004 Aug;32(8):775-8. doi: 10.1124/dmd.32.8.775. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
UGT1A1, UGT1A7, and UGT1A10 play a minor role in the formation of mycophenolic acid-7-O-glucuronide.
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A7
Uniprot ID
Q9HAW7
Uniprot Name
UDP-glucuronosyltransferase 1-7
Molecular Weight
59818.315 Da
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. [Article]
  2. Bernard O, Guillemette C: The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab Dispos. 2004 Aug;32(8):775-8. doi: 10.1124/dmd.32.8.775. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
UGT1A1, UGT1A7, and UGT1A10 play a minor role in the formation of mycophenolic acid-7-O-glucuronide.
General Function
Protein kinase c binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A10
Uniprot ID
Q9HAW8
Uniprot Name
UDP-glucuronosyltransferase 1-10
Molecular Weight
59809.075 Da
References
  1. Bernard O, Guillemette C: The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab Dispos. 2004 Aug;32(8):775-8. doi: 10.1124/dmd.32.8.775. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Bond based on evidence that suggests that UGT1A6 converts mycophenolic acid to mycophenolic acid-7-O-glucuronide in rats.
General Function
Protein homodimerization activity
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. Isoform 3 lacks trans...
Gene Name
UGT1A6
Uniprot ID
P19224
Uniprot Name
UDP-glucuronosyltransferase 1-6
Molecular Weight
60750.215 Da
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
The mycophenolic acid (MPA) metabolite 6-O-desmethyl-MPA is produced by CYP3A4 and CYP3A5.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
The mycophenolic acid (MPA) metabolite 6-O-desmethyl-MPA is produced by CYP3A4 and CYP3A5.
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
CYP2C8 may have a role in the conversion of mycophenolic acid (MPA) to 6-O-desmethyl-MPA.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
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. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: MYFORTIC (mycophenolic acid) delayed-release tablets for oral use [Link]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48