(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid

• ChemBase ID: 897
• Molecular Formular: C17H20O6
• Molecular Mass: 320.3371
• Monoisotopic Mass: 320.12598836
• SMILES: O1Cc2c(c(O)c(c(OC)c2C)C/C=C(/CCC(=O)O)\C)C1=O
• Canonical SMILES: COc1c(C/C=C(/CCC(=O)O)\C)c(O)c2c(c1C)COC2=O
• 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+
• InChIKey: HPNSFSBZBAHARI-RUDMXATFSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid; 6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
• IUPAC Traditional name: mycophenolic acid; 6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
• Brand Name: Myfortic; Melbex
• Synonyms: Mycophenolate; 6-(1,3-Dihydro-7-hydroxy-5-methoxy-4-methyl-1-oxoisobenzofuran-6-yl)-4-methyl-4-hexanoic acid; 6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid; NSC 129185; Mycophenolic acid; 6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid; (4E)-6-(1,3-Dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic Acid; 6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid; Mycophenoic acid; Mycophenolic acid; 6-[4-Hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl]-4-methyl-4-hexenoic acid

Database IDs

• CAS Number: 24280-93-1
• EC Number: 246-119-3
• MDL Number: MFCD00036814
• Beilstein Number: 1295848
• PubChem SID: 24896987; 160964360; 24896854; 46504559
• PubChem CID: 446541
• CHEBI ID: 168396
• ATC CODE: L04AA06
• CHEMBL: 866
• Chemspider ID: 393865
• DrugBank ID: DB01024
• KEGG ID: D05096
• Unique Ingredient Identifier: HU9DX48N0T
• Wikipedia Title: Mycophenolic_acid

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.574788
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 1.6079037
• LogD (pH = 7.4): 0.17404361
• Log P: 3.5275974
• Molar Refractivity: 85.2334 cm^3
• Polarizability: 32.124084 Å^3
• Polar Surface Area: 93.06 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.36
• LOG S: -3.96
• Solubility (Water): 3.55e-02 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; Ethanol; Insoluble; Methanol; methanol: soluble50 mg/mL; methanol: soluble50 mg/mL, clear, colorless to faintly yellow
• Apperance: powder; White to Off-White Solid
• Melting Point: 136-137°C; 141°C
• Hydrophobicity(logP): 2.8; 3.441

Safety Information

• Storage Condition: -20°C; -20°C Freezer; 2-8°C
• RTECS: MP8050000
• European Hazard Symbols: Nature polluting (N); Toxic (T); Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 61-22-48/25-50/53-68; R:22
• Safety Statements: 53-22-45-61; S:36/37/39
• GHS Pictograms: GHS07; GHS08; GHS09
• GHS Signal Word: Danger
• GHS Hazard statements: H302-H341-H360D-H372-H410
• GHS Precautionary statements: P201-P273-P281-P308 + P313-P501
• Personal Protective Equipment: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Storage Temperature: 2-8°C

Pharmacology Properties

• Admin Routes: Oral, IV
• Bioavailability: 94% (mofetil), 72% (sodium)
• Excretion: Renal 93%
• Half Life: 16–18 hours
• Metabolism: Hepatic
• Protein Bound: 97%
• Legal Status: S4 (Au), POM (UK), ?-only (U.S.)
• Pregnancy Category: D (Au), D (U.S.)
• US Licence: mycophenol
• EU Licence: Cellcept
• Gene Information: human ... IMPDH1(3614), IMPDH2(3615)
• Target Organ: Immune system

Product Information

• Purity: ≥98%; ≥98.0% (HPLC); 95%; 98%
• Salt Data: Free Base
• Suitability: suitable for cell culture
• Quality Level: PREMIUM
• Empirical Formula (Hill Notation): C17H20O6

DETAILS

MP Biomedicals - 02194172

From Penicillium brevi compactum
Purity: 98%

DrugBank - DB01024

• Drug 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).
• Indication: For the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.
• Pharmacology: 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.
• 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
• Biotransformation: 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.
• Absorption: Bioavailability following oral administration of Myfortic delayed-release tablet ranges from 70-95%
• 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.
• Protein Binding: >98%
• Distribution: * 54 ± 25 L
• Clearance: * 140 +/- 30 mL/min [Stable renal transplant patients]
• References: 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: Wikipedia; Drugs.com

Selleck Chemicals - S2487

Research Area: Immunology
Biological Activity:
Mycophenolic acid (mycophenolate) is an immunosuppressant agent used to prevent rejection in organ transplantation. Mycophenolic acid (mycophenolate) is derived from the fungus Penicillium stoloniferum. Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. Mycophenolic acid (mycophenolate) inhibits inosine monophosphate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes. [1] Mycophenolic acid (mycophenolate) is potent and can be used in place of the older anti-proliferative azathioprine. Mycophenolic acid (mycophenolate) is usually used as part of a three-compound regimen of immunosuppressants, also including a calcineurin inhibitor (ciclosporin or tacrolimus) and prednisolone. [2]

Sigma Aldrich - M3536

Application
Recommended for use as a selection agent at 25 μg/ml.
Used to select animal cells expressing the Escherichia coli gene for xanthine-guanine phosphosribosyl transferase.
Biochem/physiol Actions
Immunosuppressive agent. Suppresses cytokine-induced nitric oxide production.
Immunosuppressive agent. Used to inhibit early stage biosynthesis of purine nucleotides. Used as a specific inhibitor of inosine 5′-monophosphate (IMP) dehydrogenase (IMPDH) and inducer of IMP dehydrogenase gene expression.
Protocols & Applications
Antibiotic Selector for application, solubility, solution stability, working concentration, and mode of action information

Sigma Aldrich - M5255

Application
Used to select animal cells expressing the Escherichia coli gene for xanthine-guanine phosphosribosyl transferase.
Biochem/physiol Actions
Immunosuppressive agent. Suppresses cytokine-induced nitric oxide production.
Protocols & Applications
Antibiotic Selector for application, solubility, solution stability, working concentration, and mode of action information

Sigma Aldrich - 70018

Application
Used to select animal cells expressing the Escherichia coli gene for xanthine-guanine phosphosribosyl transferase.
Biochem/physiol Actions
Immunosuppressive agent. Suppresses cytokine-induced nitric oxide production.
Other Notes
Antibiotic substance. Inhibits IMP dehydrogenase1

Toronto Research Chemicals - M831500

An antibiotic produced by Penicillium brevi-compactum, P. Stoloniferum and related spp. A selective inhibitor of lymphocyte proliferation by blocking inosine monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of purine nucleotides.

REFERENCES

• 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
• Ransom JT et al. Ther Drug Monit. 1995 Dec;17(6)
• Senda, M., et al.: Transplantation, 60, 1143 (1995)
• Nimmesgern, E., et al.: J. Biol. Chem., 271, 19421 (1995)
• Gummert, J.F., et al.: J. Pharmacol. Exp. Ther., 291, 1100 (1995)