Inosine monophosphate dehydrogenase (IMPDH); de novo purine synthesis; Microbial Metabolite; Human Endogenous Metabolite

Numerous RNA viruses, such as the hantavirus, rotavirus, CCHFV, dengue virus, influenza, and Zika virus, are susceptible to the antiviral actions of mycophenolic acid [1]. The virus's rate-limiting enzyme is called IMPDH. On endothelial cells and fibroblasts, de novo mycophenolate mofetil (0.01-1 μM; 72 hours) shows selective antiproliferative action. The most susceptible cells to mycophenolic acid therapy are endothelial cells, and the antimitotic action of this compound has an IC50 < synthesis [2]. In comparison to endothelial cells, fibroblasts have a greater IC50 (<1 μM) for mycophenolic acid-induced cell cycle inhibition. A549 non-small cell lung cancer cells, 500 nM, are two human tumor cell lines [2]. and PC3 cadavers had IC50 >1 μM and modest body weight. Up to 1 μM of MPA therapy does not affect U87 astrocytes [2]. Mycophenolic acid on HDAC2 (0.05–2 μM; 18 hours)

Mycophenolic acid/MPA regulates the tumor microenvironment to greatly limit the formation of U87 tumors in BALB/c nude mice [2].
Based on our in vitro screen results, we hypothesized that the antiangiogenic effects of MPA may result in tumor growth inhibition in vivo even if the tumor cells themselves are resistant to MPA therapy. Therefore, we used the MPA-resistant human U87 tumor s.c. xenograft model in BALB/c nude mice. In support of our hypothesis, we found a significant inhibition of tumor growth (∼70% after day 14 after tumor implantation; P < 0.01) in MMF-treated versus control mice (Fig. 1B). Further, microvessel density (CD31 staining) and pericyte coverage determined by α-smooth muscle actin staining were markedly reduced in MMF-treated versus control tumors (44% and 78%, respectively; Fig. 1C). These data emphasize the importance of tumor microenvironment and, in particular, tumor vessels in MPA-induced antitumor effects [2].

In vitro Angiogenesis Assays [2]
All in vitro assays were done as described previously (9, 11–14). For proliferation assay, cells were harvested by trypsinization at 37°C and neutralized with trypsin-neutralizing solution. A suspension of 50,000 cells in modified Promocell medium/DMEM was added to 25 cm2 flasks. After 24 h, cells were incubated with MPA at the indicated dose and incubated for another 72 h and then counted. For the tube formation assays, 24-well plates were coated with 300 μL Matrigel, cells were plated, and after 12-h incubation, cells were fixed and stained with Diff-Quick II reagents. For invasion/migration assay, Matrigel-coated (0.78 mg/mL) Transwells with 8 μm pore size were used. The HDMVEC or fibroblasts were added to the Transwells (upper compartment). Chemoattractant medium containing 2 ng/mL vascular endothelial growth factor and 4 ng/mL basic fibroblast growth factor (500 μL) was added to 24-well plates (lower wells). The Transwells were transferred to the 24-well plates, and after 18 h of incubation, cells that had invaded the underside of the membrane were fixed and stained with Diff-Quick II solution, sealed on slides, and counted by microscopy (number of migrated cells per eight optical fields at ×40 objective and ×10 oculars). Experiments were done at least in quadruplicates.

cell proliferation assay [2]
Cell Types: primary isolated human dermal microvascular endothelial cells (HDMVEC), fibroblasts, U87 glioblastoma cells, PC3 prostate cancer In cells, A549 non- and MYC exhibit debt invoicing, which is upregulated by NDRG1[2]. Small cell lung cancer cells
Tested Concentrations: 0.01, 0.1, 1 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: demonstrated preferential anti-proliferative activity on HDMVEC and fibroblasts. U87 glioblastoma cells were resistant to treatment, whereas A549 non-small cell lung cancer and PC3 prostate cancer cells demonstrated intermediate sensitivity.

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Western Blot Analysis[2]
Cell Types: HDMVEC
Tested Concentrations: 0, 0.05, 0.1, 0.5, 1 and 2 μM
Incubation Duration: 18 hrs (hours)
Experimental Results: Shows dose-dependent regulation of HDAC2, MYC and NDRG1.

Animal/Disease Models: Athymic 8weeks old, 20 g BALB/c nu/nu mycophenolic acid-bearing mouse drug-resistant human U87 tumor model [2]
Doses: 120 mg/kg MMF (mycophenolate mofetil prodrug) Mode of
Route of Administration: po (oral gavage); bid
Experimental Results: Compared with control mice, MMF (mycophenolate mofetil prodrug) Dramatically inhibited tumor growth in MMF-treated mice (approximately 14 days after tumor implantation) 70%). Microvessel density (CD31 staining) and pericyte coverage measured by α-smooth muscle actin staining were Dramatically diminished in MMF-treated tumors compared with control tumors (44% and 78%, respectively).

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Animal Studies and Immunohistology [2]
The animal experiments were conducted according to the guidelines of the German Animal Protection Law and approved by the state agency supervising animal experimentation. For tumor growth experiments, athymic 8-week-old, 20 g BALB/c nu/nu mice were used. Human U87 glioblastoma cells (5 × 106 in 100 μL PBS) were injected s.c. into the right hind limb of the mice. Tumor volume was determined by caliper measurements using the formula: volume V = length × width × width × 0.5. Animals were treated with 120 mg/kg b.i.d. oral gavage MMF, the morpholinoethyl ester prodrug of MPA. Treatment started 45 h after s.c. tumor cell injection. For histologic analysis, tumors were excised and snap frozen in isopentane, cooled by liquid nitrogen, and kept at −80°C. Frozen tissues were sectioned (6 μm), mounted on silan-coated slides, and fixed in ice-cold methanol (1 min) and acetone (2 min). After washing with 1× PBS (pH 7.2), the sections were incubated with Image-iT FX signal enhancer for 30 min. Nonspecific binding was blocked with 0.25% casein in PBS for 30 min.

Absorption, Distribution and Excretion
Mycophenolic acid exhibits linear and dose-proportional pharmacokinetics within a dose range of 360 mg to 2160 mg. Enteric coating of mycophenolic acid tablets prevents release in acidic environments (stomach, pH < 5). However, enteric-coated mycophenolic acid tablets have high solubility in neutral pH environments (e.g., the intestines). In kidney transplant patients, the median time lag (Tlag) for mycophenolic acid concentration rise was 0.25 to 1.25 hours, and the time to peak concentration (Tmax) was 1.5 to 2.75 hours. In adult kidney transplant patients receiving cyclosporine treatment who also received mycophenolic acid, the Tmax was 2 hours, the Cmax was 26.1 μg/mL, and the AUC0-12 was 66.5 μg⋅h/mL. In stable pediatric (5-16 years) kidney transplant patients, Cmax and AUC were 33% and 18% higher, respectively, than in adults. In stable kidney transplant patients receiving cyclosporine therapy, the gastrointestinal absorption and absolute bioavailability of mycophenolate mofetil were 93% and 72%, respectively. After consuming a high-fat meal (55 g fat, 1000 calories), the AUC of mycophenolate mofetil (enteric-coated tablets, 720 mg) was comparable to that measured on an empty stomach. However, a high-fat meal resulted in a 33% decrease in Cmax, a 3.5-hour delay in Tlag (range -6 to 18 hours), and a 5.0-hour delay in Tmax (range -9 to 20 hours). To avoid variability in mycophenolate mofetil absorption, this medication should be taken on an empty stomach. In stable kidney transplant patients, approximately 60% of mycophenolate mofetil is excreted in the urine as mycophenolate glucuronide (MPAG), while 3% is excreted unchanged. MPAG is also secreted into bile and can be deconjugated by intestinal flora. Mycophenolic acid, produced by MPAG deconjugation, may be reabsorbed, with a second peak plasma concentration occurring 6-8 hours after administration. At steady state, the volume of distribution of mycophenolic acid is 54 L. During elimination, the volume of distribution is 112 L. 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. Mycophenolic acid is primarily metabolized by glucuronyltransferase to produce glucuronidated metabolites. Mycophenolic acid glucuronide (MPAG) is the major metabolite of mycophenolic acid and has no pharmacological activity. However, the minor metabolite, acylglucuronide, has similar pharmacological activity to mycophenolic acid. At steady state, the AUC ratio of mycophenolic acid, mycophenolic glucuronide, and acylglucuronide is approximately 1:24:0.28. Known metabolites of mycophenolic acid include mycophenolic glucuronide and 6-O-demethylmycophenolic acid (DM-MPA). Mycophenolic acid is primarily metabolized by glucuronyltransferases to glucuronidated metabolites, the most important of which is phenolic glucuronide, namely mycophenolic glucuronide (MPAG). MPAG is pharmacologically inactive. Acylglucuronide is a minor metabolite with similar pharmacological activity to mycophenolic acid. At steady state, the AUC ratio of mycophenolic acid, MPAG, and acylglucuronide is approximately 1:24:0.28. Half-life: The mean elimination half-life of mycophenolic acid is 8–16 hours, while the mean elimination half-life of its major metabolite, MPAG, is 13–17 hours.

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Biological Half-Life
Mycophenolic acid has an average elimination half-life of 8-16 hours, while its main metabolite, mycophenolic acid glucuronide, has an average elimination half-life of 13-17 hours.

Hepatotoxicity
A small number of patients taking mycophenolate mofetil may experience elevated serum enzymes, but these abnormalities are usually mild, asymptomatic, and resolve spontaneously or with dose reduction. There have been a few reported cases of clinically significant liver injury in patients taking mycophenolate mofetil. The injury typically occurs within the first month of treatment, with serum enzyme elevations in a hepatocellular or mixed pattern. Liver injury is usually mild and self-limiting. Autoimmune and immunohypersensitivity features are uncommon. Probability score: D (Possibly a rare cause of clinically significant liver injury).

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Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Information regarding mycophenolate mofetil being excreted into breast milk comes from 3 patients, but the results are inconsistent. A small number of infants have been reported to be breastfed during mycophenolate mofetil treatment without adverse reactions. Due to limited information on the use of mycophenolate mofetil during lactation, alternative medications may be preferred, especially when breastfeeding newborns or preterm infants.
◉ Effects on Breastfed Infants
The U.S. National Transplant Pregnancy Registry (now the International Transplant Pregnancy Registry) collected information from six mothers (five kidney transplant recipients and two heart transplant recipients) who breastfed seven infants while taking mycophenolate mofetil. The longest breastfeeding period for any of the infants was 14 months. No adverse events were reported in any of the infants. Another case series reported by the International Transplant Pregnancy Registry reported that three women who received heart transplants breastfed while taking mycophenolate mofetil. This series did not mention the duration of breastfeeding or the infant outcomes. Some of these women may be similar to those in the case series mentioned above.
In a UK case series study involving 77 patients who received liver or heart/chest transplants, nine patients took mycophenolate mofetil throughout their pregnancy. Overall, 60% of the patients breastfed, but the study did not report the specific number of women who breastfed while taking mycophenolate mofetil or the outcomes.
An Australian case series reported on three women who received heart transplants and gave birth to five infants, all of whom were breastfed (the extent of breastfeeding was not specified). Two of the women took mycophenolate mofetil postpartum; one woman received 720 mg twice daily, and the other received 1 g twice daily. No adverse reactions were reported in the infants at discharge.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.
◈ What is Mycophenolate Mofetil?
Mycophenolate mofetil is a medication used to treat certain autoimmune diseases, such as rheumatoid arthritis and lupus. Mycophenolate mofetil can also be used to help prevent rejection of transplanted organs after organ transplantation, such as kidney transplantation. The mechanism of action of mycophenolate mofetil is to reduce the immune system (the body's defense system against harmful substances and bacteria). Mycophenolate mofetil is marketed under the brand name Cellcept®. A similar drug called mycophenolic acid is marketed under the brand name Myfortic®. For more information on rheumatoid arthritis and lupus, please see the information sheets on the MotherToBaby website: https://mothertobaby.org/fact-sheets/rheumatoid-arthritis/ and https://mothertobaby.org/fact-sheets/lupus-pregnancy/. Sometimes, when people find out they are pregnant, they consider changing their medication regimen or even stopping it entirely. However, it is essential to talk to your healthcare provider before changing your medication regimen. Your healthcare provider can discuss with you the benefits of treating your condition and the risks of not treating the condition during pregnancy.
◈ I am taking mycophenolate mofetil, but I want to stop taking it before I get pregnant. How long will this medication stay in my body?
Everyone's drug metabolism rate is different. For healthy adults, on average, mycophenolate mofetil takes about a week to be metabolized and cleared from the body.
◈ I am taking mycophenolate mofetil. Will it affect my pregnancy?
It is currently unclear whether mycophenolate mofetil affects pregnancy. The U.S. Food and Drug Administration (FDA) requires individuals who may become pregnant to attend the Mycophenolate Mofetil (MPM) Education Program before starting mycophenolate mofetil. Healthcare professionals prescribing mycophenolate mofetil must also attend the program. The program requires a negative pregnancy test before starting mycophenolate mofetil and a negative pregnancy test 8 to 10 days after starting treatment. The program also recommends using effective contraception while taking mycophenolate mofetil. After discontinuing mycophenolate mofetil, contraception should be continued for 6 weeks. It is important to note that mycophenolate mofetil may reduce the effectiveness of hormonal contraceptives, such as birth control pills.
◈ Does taking mycophenolate mofetil increase the risk of miscarriage?
Miscarriage is common and can occur in any pregnancy for a variety of reasons. Taking mycophenolate mofetil during pregnancy increases the risk of miscarriage. One report suggests that the risk of miscarriage with mycophenolate mofetil during pregnancy may be close to 50% (one in two pregnancies). Because some conditions treated with mycophenolate mofetil can themselves increase the risk of miscarriage, it is difficult to determine whether a miscarriage is caused by the medication, the condition, or other factors.
◈ Does taking mycophenolate mofetil increase the risk of birth defects?
There is a 3-5% risk of birth defects in each pregnancy, known as the baseline risk. Taking mycophenolate mofetil during pregnancy may increase the risk of birth defects. Some reported patterns of birth defects include abnormally small or missing ears, eyes, and/or jaw; heart defects; cleft lip and/or cleft palate (a cleft in the lip or roof of the mouth), etc. Affected children may have only one birth defect or a combination of multiple birth defects. Not all children exposed to mycophenolate mofetil during pregnancy will develop birth defects.
◈ Does taking mycophenolate mofetil during pregnancy increase the risk of other pregnancy-related problems?
It is currently unclear whether mycophenolate mofetil causes other pregnancy-related problems such as preterm birth (delivery before 37 weeks of gestation) or low birth weight (birth weight less than 5 pounds 8 ounces [2500 grams]).
◈ Will taking mycophenolate mofetil during pregnancy affect my child's future behavior or learning abilities?
It is currently unclear whether mycophenolate mofetil increases the risk of behavioral or learning problems in children.
◈ What screenings or tests can determine if my fetus has birth defects or other problems?
Prenatal ultrasound can be used to screen for certain birth defects, such as defects of the ears, eyes, jaw, heart, lips, and palate. Ultrasound can also be used to monitor fetal growth and development. Please consult your healthcare provider about any prenatal screenings or tests you can have. There are currently no tests during pregnancy that can assess the extent to which mycophenolate mofetil will affect future behavior or learning abilities.
◈ Breastfeeding while taking mycophenolate mofetil:
It is currently unclear how much mycophenolate mofetil passes into breast milk. Limited reports indicate no harmful effects on infants after exposure to mycophenolate mofetil through breast milk. Be sure to consult your healthcare provider about all breastfeeding-related questions.
◈ Does taking mycophenolate mofetil affect fertility or increase the risk of birth defects in men? Currently, no studies have explored whether mycophenolate mofetil affects male fertility (the ability to impregnate a partner). Three studies investigated the infants born to 356 men who took mycophenolate mofetil around the time of conception and found no increase in birth defects. Another report, including children born to 255 men who took mycophenolate mofetil, also showed no increase in miscarriage or birth defects. Out of theoretical concern (rather than proven risk), some healthcare providers may recommend that men taking mycophenolate mofetil wait at least three months after stopping the medication before attempting pregnancy. Generally, exposure to mycophenolate mofetil by the father or sperm donor is unlikely to increase the risk of pregnancy. For more information, please see the “Paternal Exposure” information sheet on the MotherToBaby website at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/. Mycophenolate mofetil is highly bound to proteins, with over 98% binding to albumin.

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Toxicity Overview
Mycophenolic acid is a potent, selective, non-competitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), thus inhibiting the de novo guanylate synthesis pathway without incorporation into DNA. Because T cell and B cell proliferation heavily depends on de novo purine synthesis, while other cell types can utilize salvage pathways, mycophenolic acid exhibits strong cytoseptic effects on lymphocytes. Mycophenolic acid inhibits the proliferative response of T cells and B cells to mitogens and allogeneic stimuli. The addition of guanosine or deoxyguanosine reverses the cytoseptic effect of mycophenolic acid on lymphocytes. Mycophenolic acid also inhibits antibody production by B lymphocytes. Mycophenolic acid prevents the glycosylation of lymphocyte and monocyte glycoproteins involved in intercellular and endothelial cell adhesion and may inhibit the recruitment of leukocytes to sites of inflammation and transplant rejection.

[1]. Screening and Identification of Lujo Virus Inhibitors Using a Recombinant Reporter Virus Platform. Viruses. 2021 Jun 28;13(7):1255.

[2]. Molecular mechanisms of the antiangiogenic and antitumor effects of mycophenolic acid. Mol Cancer Ther. 2008 Jun;7(6):1656-68.

Mycophenolic acid belongs to the 2-benzofuran class of compounds, with the structure 2-benzofuran-1(3H)-one, where the 4, 5, 6, and 7 positions are substituted with methyl, methoxy, (2E)-5-carboxy-3-methylpent-2-en-1-yl, and hydroxyl groups, respectively. It is an antibiotic produced by Penicillium brevi-compactum, Penicillium stoloniferum, Penicillium echinulatum, and their close relatives. As an immunosuppressant, mycophenolic acid (especially its sodium salt and prodrug 2-(morpholino-4-yl)ethyl ester, i.e., mycophenolic acid ester) is widely used to prevent tissue rejection after organ transplantation and to treat certain autoimmune diseases. It possesses various activities, including antitumor activity, antibacterial activity, EC 1.1.1.205 (IMP dehydrogenase) inhibitor, immunosuppressant, mycotoxin, Penicillium metabolites, environmental pollutants, exogenous substances, and anticoronavirus drugs. It is a γ-lactone, belonging to the phenolic, monocarboxylic acid, and 2-benzofuran classes. Its function is related to hexanoic acid. It is the conjugate acid of mycophenolic acid esters. Mycophenolic acid is a potent immunosuppressant that inhibits de novo purine synthesis. It is derived from Penicillium stoloniferum and has been shown to possess antibacterial, antifungal, and antiviral properties. Mycophenolic acid is commonly used in immunosuppressive regimens as part of triple therapy, which also includes calcineurin inhibitors (cyclosporine or tacrolimus) and prednisolone. Due to its stronger immunosuppressive potency, this regimen can replace older antiproliferative drugs [azathioprine]. However, mycophenolic acid treatment is more expensive and requires therapeutic monitoring to optimize efficacy and minimize toxicity. Mycophenolic acid is available in enteric-coated extended-release tablets, designed to improve upper gastrointestinal adverse reactions by delaying the release of mycophenolic acid until it reaches the small intestine. Mycophenolate mofetil (a prodrug of mycophenolic acid) is also used to prevent organ transplant rejection. Mycophenolic acid is an antimetabolite immunosuppressant. Mycophenolate mofetil is an antimetabolite and potent immunosuppressant used as adjunctive therapy to prevent allogeneic transplant rejection and to treat severe autoimmune diseases. Mycophenolate mofetil treatment may cause mild elevation of serum enzymes and has been associated with rare cases of clinically significant liver injury. Mycophenolic acid has been reported in Colletotrichum sublineola, Penicillium griseofulvum, and other microorganisms with relevant data. Mycophenolic acid is an antitumor antibiotic derived from various Penicillium fungi. Mycophenolic acid is the active metabolite of the prodrug mycophenolate mofetil. Mycophenolic acid inhibits inosine monophosphate dehydrogenase (IMPDH), preventing the formation of guanosine monophosphate and the synthesis of lymphocyte DNA, thereby inhibiting lymphocyte proliferation, antibody production, cell adhesion, and the migration of T cells and B cells. Mycophenolic acid also possesses antibacterial, antifungal, and antiviral activities. (NCI04)
Mycophenolate ester is the morpholine ethyl ester of mycophenolic acid (MPA). As an in vivo immunosuppressant, its active metabolite, mycophenolate ester, reversibly inhibits inosine 5'-monophosphate dehydrogenase (IMPDH), an enzyme involved in the de novo synthesis of guanine nucleotides, thereby delaying the proliferation of T cells and B cells. Because lymphocyte metabolism is highly dependent on the salvage and de novo synthesis of guanine nucleotides, MPA exhibits high lymphocyte specificity and cytotoxicity. (NCI04)
Mycophenolic acid is an immunosuppressant and a potent antiproliferator, an alternative to the older antiproliferator azathioprine. It is commonly used as part of triple therapy, which includes calcineurin inhibitors (cyclosporine or tacrolimus) and prednisolone. It is also used in research to screen animal cells expressing the E. coli gene encoding XGPRT (xanthine-guanine phosphoribosyltransferase). Mycophenolic acid is a compound derived from Penicillium lycopersicum and its close relatives. It blocks the de novo synthesis of purine nucleotides by inhibiting inosine monophosphate dehydrogenase (IMP dehydrogenase). Mycophenolic acid has a selective effect on the immune system, inhibiting the proliferation of T cells and lymphocytes and the production of antibodies by B cells. It can also inhibit the recruitment of leukocytes to sites of inflammation. See also: Mycophenolate mofetil (active ingredient); Mycophenolate sodium (salt form); Mycophenolate mofetil hydrochloride (active ingredient)... See more...

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Drug Indications
Mycophenolic acid is an antimetabolite immunosuppressant indicated for the prevention of organ rejection in adult patients who have received kidney transplantation and in children aged 5 years and older at least 6 months post-transplantation. Mycophenolic acid is usually used in combination with cyclosporine and corticosteroids.

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Mechanism of Action
Mycophenolic acid (MPA) is a selective, non-competitive, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) that blocks the conversion of inosine-5-phosphate and xanthine-5-phosphate to guanosine-5-phosphate. By inhibiting IMPDH, mycophenolic acid interferes with the de novo guanosine nucleotide synthesis pathway, preventing its incorporation into DNA. While other cell types can utilize salvage pathways, the proliferation mechanisms of T cells and B cells are highly dependent on the de novo synthesis of purines. Therefore, mycophenolic acid exhibits potent cytoseptic effects on T cells, B cells, and lymphocytes. Mycophenolic acid also inhibits antibody production in B lymphocytes and prevents the glycosylation of lymphocyte and monocyte glycoproteins involved in cell-to-cell and endothelial cell adhesion. Patients treated with the immunosuppressant mycophenolic acid (MPA) appear to have a reduced relative risk of developing malignant tumors after solid organ transplantation. However, the molecular mechanisms of MPA's antitumor effects are not fully elucidated. This article reports that human endothelial cells and fibroblasts are highly sensitive to MPA treatment. We found that U87 glioblastoma cells were resistant to MPA treatment in vitro. However, in BALB/c nude mice, the growth of U87 tumors was significantly inhibited, indicating that MPA exerts its anti-tumor effect by modulating the tumor microenvironment. Correspondingly, in vivo, MPA-treated tumors showed significantly reduced microvessel density and pericyte coverage. Through in vitro functional experiments, we found that MPA effectively inhibited the proliferation, invasion/migration, and tubular formation of endothelial cells and fibroblasts. To identify the genes regulating the anti-angiogenic and anti-fibrotic effects of MPA, we performed whole-genome transcriptome analysis on U87 cells, endothelial cells, and fibroblasts at 6 and 12 hours after MPA treatment. Network analysis revealed that the MYC signaling pathway plays a key role in MPA-treated endothelial cells. Furthermore, we found that the anti-angiogenic effect of MPA is achieved through the synergistic effect between MYC and the NDRG1, YYI, HIF1A, HDAC2, CDC2, GSK3B, and PRKACB signaling pathways. Real-time quantitative reverse transcription PCR and protein analysis confirmed the regulation of these "hub nodes". Gene knockdown experiments further showed that MYC plays a key role in the anti-angiogenic signaling pathway of MPA. In summary, these data provide a molecular basis for the anti-angiogenic and anti-fibrotic effects of MPA and are worthy of further clinical research. [2]

C23H31NO7

433.495

320.125

C, 63.73; H, 7.21; N, 3.23; O, 25.84

24280-93-1

Mycophenolic acid-d3;1185242-90-3; Mycophenolic acid sodium; 37415-62-6; Mycophenolic acid-13C17; 1202866-92-9; 66341-85-3 (triethylamine)

446541

White to off-white solid powder

1.3±0.1 g/cm3

611.6±55.0 °C at 760 mmHg

141°C

225.8±25.0 °C

0.0±1.8 mmHg at 25°C

1.585

2.92

2

6

6

23

486

0

O1C(C2=C(C(C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])C([H])([H])C(=O)O[H])=C(C(C([H])([H])[H])=C2C1([H])[H])OC([H])([H])[H])O[H])=O

RTGDFNSFWBGLEC-SYZQJQIISA-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+

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

Mycophenolic acid; mycophenolic acid; 24280-93-1; Melbex; Mycophenolsaeure; Acido micofenolico; Acide mycophenolique; Lilly-68618; Micofenolico acido; Mycophenolate mofetil; RS-61443; Myfortic; Cellcept

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~64 mg/mL (~199.8 mM)
Ethanol: ~32 mg/mL (~99.9 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 33.33 mg/mL (104.05 mM) in Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)