MYCOPHENOLIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H20O6
Molecular Weight	320.3371
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(C)C2=C(C(=O)OC2)C(O)=C1C\C=C(/C)CCC(O)=O

InChI

InChIKey=HPNSFSBZBAHARI-RUDMXATFSA-N

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+

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050791s024lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27903231

Mycophenolic acid (MPA) possesses antibacterial, antifungal, antiviral, immunosuppressive and anticancer properties. Mycophenolic acid (MPA) is a fungal metabolite that was initially discovered by Bartolomeo Gosio in 1893 as an antibiotic against anthrax bacillus, Bacillus anthracis. It is an uncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation to DNA. It was approved under the brand name Myfortic for the prophylaxis of organ rejection in adult patients receiving a kidney transplant and is indicated for the prophylaxis of organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant. Myfortic is to be used in combination with cyclosporine and corticosteroids.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Inosine-5'-monophosphate dehydrogenase (IMPDH) 11 Target ID: CHEMBL2111369 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15803924 \| https://www.ncbi.nlm.nih.gov/pubmed/10878285	Inhibitor 8297
Inosine-5'-monophosphate dehydrogenase (IMPDH) 11 Target ID: CHEMBL2111369 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11880114	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Organ transplant rejection 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050791s024lbl.pdf	Preventing		Approved 8429	MYFORTIC Approved Use Myfortic (mycophenolic acid) is indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. Myfortic is indicated for the prophylaxis of organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant. Myfortic is to be used in combination with cyclosporine and corticosteroids. Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
18.9 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050791s019lbl.pdf	720 mg 2 times / day multiple, oral dose: 720 mg route of administration: Oral experiment type: MULTIPLE co-administered: CYCLOSPORINE	CYCLOSPORINE	MYCOPHENOLIC ACID unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
57.4 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050791s019lbl.pdf	720 mg 2 times / day multiple, oral dose: 720 mg route of administration: Oral experiment type: MULTIPLE co-administered: CYCLOSPORINE	CYCLOSPORINE	MYCOPHENOLIC ACID unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.7 h DRUG LABEL https://www.novartis.com.sg/system/files/product-info/MYFORTIC%20PI%20Nov2013.SINv1_.pdf	720 mg 2 times / day multiple, oral dose: 720 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MYCOPHENOLIC ACID unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278	CYP3A4/5 85 P-gp 1537 UGT 192 CYP2C8 693 CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C18 138 CYP2C19 991 CYP2E1 667 CYP3A7 110 UGT1A9 380 UGT1A1 418 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A10 291 UGT2B4 249 UGT2B7 389 UGT1A3 422 UGT1A4 347

Drug as perpetrator

Target	Modality	Activity
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=21 Page: 21.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=21 Page: 21.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=21 Page: 21.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=21 Page: 21.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=21 Page: 21.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=21 Page: 21.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=21 Page: 21.0	weak [Ki 57 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=6 Page: 6.0	weak [Ki 98 uM]

Drug as victim

Target	Modality	Activity
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	likely
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=5 Page: 5.0	major
CYP3A4/5 85	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	minor
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP2C18 138	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
CYP3A7 110	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15570183/ Page: -	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/50-791_Myfortic_biopharmr.PDF#page=22 Page: 22.0	no
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	no
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	no
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	no
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	no
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	yes [Km 1390 uM]
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	yes [Km 160 uM]
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	yes [Km 200 uM]
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	yes [Km 410 uM]
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	yes [Km 480 uM]
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15470161/ Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:168396	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:168396
ChemicalBook	CB4507365	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4507365
ChemicalBook	CB8311003	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8311003
MolPort	MolPort-001-732-316	https://www.molport.com/shop/molecule-link/MolPort-001-732-316
Selleck Chemicals	Mycophenolic-acid(Mycophenolate)	http://www.selleckchem.com/products/Mycophenolic-acid(Mycophenolate).html
ZINC	ZINC000000001758	http://zinc15.docking.org/substances/ZINC000000001758
eMolecules	18595868	https://www.emolecules.com/cgi-bin/more?vid=18595868

PubMed

Title	Date	PubMed
		96279836
Polymerase substrate depletion: a novel strategy for inhibiting the replication of the human immunodeficiency virus.	1995 Aug 20	7544050
Abacavir and mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase, have profound and synergistic anti-HIV activity.	1999 Aug 15	10458616
Novel mycophenolic adenine bis(phosphonate)s as potential immunosuppressants.	1999 Jul	10390605
The effect of mycophenolate mofetil and polyphenolic bioflavonoids on renal ischemia reperfusion injury and repair.	2000 Mar	10688038
Mycophenolate mofetil and its mechanisms of action.	2000 May	10878285
Mycophenolate mofetil treatment accelerates recovery from experimental allergic encephalomyelitis.	2001 Sep	11562063
Dose proportional inhibition of HIV-1 replication by mycophenolic acid and synergistic inhibition in combination with abacavir, didanosine, and tenofovir.	2002 Jul	12076750
Characterization of wild-type and cidofovir-resistant strains of camelpox, cowpox, monkeypox, and vaccinia viruses.	2002 May	11959564
Mycophenolic acid inhibits IL-2-dependent T cell proliferation, but not IL-2-dependent survival and sensitization to apoptosis.	2002 Sep 1	12193749
Anti-HIV-1 activity of leflunomide: a comparison with mycophenolic acid and hydroxyurea.	2003 Jul 25	12853743
Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus.	2003 Jun 14	12814717
The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA.	2003 Jun 5	12781720
Characterization of a phase 1 metabolite of mycophenolic acid produced by CYP3A4/5.	2004 Dec	15570183
In vitro combination of amdoxovir and the inosine monophosphate dehydrogenase inhibitors mycophenolic acid and ribavirin demonstrates potent activity against wild-type and drug-resistant variants of human immunodeficiency virus type 1.	2004 Nov	15504868
Mycophenolic acid inhibits avian reovirus replication.	2004 Oct	15451179
Mechanisms of action of mycophenolate mofetil.	2005	15803924
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in maintenance renal transplant recipients receiving tacrolimus: clinical, pharmacokinetic, and pharmacodynamic outcomes.	2007 Feb 27	17318074
Real-time PCR determination of IMPDH1 and IMPDH2 expression in blood cells.	2007 Jun	17463174
Current target ranges of mycophenolic acid exposure and drug-related adverse events: a 5-year, open-label, prospective, clinical follow-up study in renal allograft recipients.	2008 Apr	18498916
Effect of D256N and Y483D on propofol glucuronidation by human uridine 5'-diphosphate glucuronosyltransferase (UGT1A9).	2008 Aug	18816295
Mycophenolic acid inhibits cell proliferation and extracellular matrix synthesis in rat vascular smooth muscle cells through direct and indirect inhibition of cellular reactive oxygen species.	2008 Nov	17950325
The necrotic signal induced by mycophenolic acid overcomes apoptosis-resistance in tumor cells.	2009	19430526
Antiviral activity of indole derivatives.	2009 Aug	19445965
Mycophenolic acid in rheumatology: mechanisms of action and severe adverse events.	2010 Apr-Jun	20657885
Mycophenolic acid inhibits the phosphorylation of NF-kappaB and JNKs and causes a decrease in IL-8 release in H2O2-treated human renal proximal tubular cells.	2010 May 14	20302854
Mycophenolic acid inhibits natural killer cell proliferation and cytotoxic function: a possible disadvantage of including mycophenolate mofetil in the graft-versus-host disease prophylaxis regimen.	2011 Feb	20736080
Effects of mycophenolic acid alone and in combination with its metabolite mycophenolic acid glucuronide on rat embryos in vitro.	2013 Feb	22914985
Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines.	2013 Nov	23999140
Characterization of the zebrafish Ugt repertoire reveals a new class of drug-metabolizing UDP glucuronosyltransferases.	2014 Jul	24728488
Transcriptome-based functional classifiers for direct immunotoxicity.	2014 Mar	24356939
Effect of Penicillium mycotoxins on the cytokine gene expression, reactive oxygen species production, and phagocytosis of bovine macrophage (BoMacs) function.	2015 Dec 25	26394380
Screening of a chemical library reveals novel PXR-activating pharmacologic compounds.	2015 Jan 5	25455453

Patents

Sample Use Guides

In Vivo Use Guide

Dosage in Adult Kidney Transplant Patients: the recommended dose of Myfortic is 720 mg administered twice daily (1440 mg total daily dose). Dosage in Pediatric Kidney Transplant Patients: the recommended dose of Myfortic in conversion (at least 6 months post-transplant) pediatric patients age 5 years and older is 400 mg/m2 body surface area (BSA) administered twice daily (up to a maximum dose of 720 mg administered twice daily. Administration Myfortic tablets should be taken on an empty stomach, 1 hour before or 2 hours after food intake

Route of Administration: Oral

In Vitro Use Guide

It was investigated the antiviral activity and mechanism of action of mycophenolic acid (MPA) against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM).

Name

Type

Language

MYCOPHENOLIC ACID

Official Name

English

MYCOPHENOLATE [VANDF]

Common Name

English

4-HEXENOIC ACID, 6-(1,3-DIHYDRO-4-HYDROXY-6-METHOXY-7-METHYL-3-OXO-5-ISOBENZOFURANYL)-4-METHYL-, (E)-

Common Name

English

MYCOPHENOLATE

Common Name

English

MYCOPHENOLIC ACID [MART.]

Common Name

English

NSC-129185

Code

English

MYCOPHENOLATE MOFETIL IMPURITY F [EP IMPURITY]

Common Name

English

MYCOPHENOLIC ACID [VANDF]

Common Name

English

68618

Code

English

Mycophenolic acid [WHO-DD]

Common Name

English

MYCOPHENOLATE MOFETIL IMPURITY, MYCOPHENOLIC ACID- [USP IMPURITY]

Common Name

English

(4E)-6-(4-HYDROXY-6-METHOXY-7-METHYL-3-OXO-1,3-DIHYDRO-2-BENZOFURAN-5-YL)-4-METHYLHEX-4-ENOIC ACID

Systematic Name

English

(E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid

Common Name

English

mycophenolic acid [INN]

Common Name

English

MYCOPHENOLIC ACID [MI]

Common Name

English

4-HEXENOIC ACID, 6-(1,3-DIHYDRO-4-HYDROXY-6-METHOXY-7-METHYL-3-OXO-5-ISOBENZOFURANYL)-4-METHYL-, (4E)-

Common Name

English

MYCOPHENOLIC ACID [ORANGE BOOK]

Common Name

English

MYFORTIC

Brand Name

English

MYCOPHENOLIC ACID [USAN]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548945