肌苷单磷酸脱氢酶是 T 淋巴细胞和 B 淋巴细胞用于从头产生鸟苷核苷酸的关键酶 [1]。

在 ACI-to-Lewis 大鼠异位心脏移植模型中，20 mg/kg 和 40 mg/kg 剂量的吗替麦考酚酯治疗可延长移植物存活时间，中位存活时间 (MST) 分别为 14.5 天和 18.5 天， 分别。在博莱霉素 (BLM) 诱导的硬皮病小鼠模型中，吗替麦考酚酯可减少炎症细胞浸润、组织羟脯氨酸含量和真皮厚度。

Absorption, Distribution and Excretion
Mycophenolate mofetil is rapidly absorbed in the small intestine. The maximum concentration of its active metabolite, MPA, is attained 60 to 90 minutes following an oral dose. The average bioavailability of orally administered mycophenolate mofetil in a pharmacokinetic study of 12 healthy patients was 94%. In healthy volunteers, the Cmax of mycophenolate mofetil was 24.5 (±9.5)μg/mL. In renal transplant patients 5 days post-transplant, Cmax was 12.0 (±3.82) μg/mL, increasing to 24.1 (±12.1)μg/mL 3 months after transplantation. AUC values were 63.9 (±16.2) μg•h/mL in healthy volunteers after one dose, and 40.8 (±11.4) μg•h/mL, and 65.3 (±35.4)μg•h/mL 5 days and 3 months after a renal transplant, respectively. The absorption of mycophenolate mofetil is not affected by food.
A small amount of drug is excreted as MPA in the urine (less than 1%). When mycophenolate mofetil was given orally in a pharmacokinetic study, it was found to be 93% excreted in urine and 6% excreted in feces. Approximately 87% of the entire administered dose is found to be excreted in the urine as MPAG, an inactive metabolite.
The volume of distribution of mycophenolate mofetil is 3.6 (±1.5) to 4.0 (±1.2) L/kg.
Plasma clearance of mycophenolate mofetil is 193 mL/min after an oral dose and 177 (±31) mL/min after an intravenous dose.
/Absorption/ is rapid and extensive after oral administration.
In 12 healthy volunteers, the mean absolute bioavailability of oral mycophenolate mofetil relative to intravenous mycophenolate mofetil (based on MPA AUC) was 94%. The area under the plasma-concentration time curve (AUC) for MPA appears to increase in a dose-proportional fashion in renal transplant patients receiving multiple doses of mycophenolate mofetil up to a daily dose of 3 g.
Protein binding: To plasma albumin: High (97% for mycophenolic acid (MPA) at concentration ranges normally seen in stable renal transplant patients). At higher mycophenolic acid glucuronide (MPAG) concentrations (e.g., in patients with renal impairment or delayed graft function), binding of MPA may be decreased as a result of competition between MPA and MPAG for binding sites.
The mean (+/-SD) apparent volume of distribution of MPA in 12 healthy volunteers is approximately 3.6 (+/-1.5) and 4.0 (+/-1.2) L/kg following intravenous and oral administration, respectively. MPA, at clinically relevant concentrations, is 97% bound to plasma albumin. MPAG is 82% bound to plasma albumin at MPAG concentration ranges that are normally seen in stable renal transplant patients; however, at higher MPAG concentrations (observed in patients with renal impairment or delayed renal graft function), the binding of MPA may be reduced as a result of competition between MPAG and MPA for protein binding. Mean blood to plasma ratio of radioactivity concentrations was approximately 0.6 indicating that MPA and MPAG do not extensively distribute into the cellular fractions of blood.
For more Absorption, Distribution and Excretion (Complete) data for MYCOPHENOLATE MOFETIL (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
After both oral and intravenous administration mycophenolate mofetil is entirely metabolized by liver carboxylesterases 1 and 2 to mycophenolic acid (MPA), the active parent drug. It is then metabolized by the enzyme glucuronyl transferase, producing the inactive phenolic glucuronide of MPA (MPAG). The glucuronide metabolite is important, as it is then converted to MPA through enterohepatic recirculation. Mycophenolate mofetil that escapes metabolism in the intestine enters the liver via the portal vein and is transformed to pharmacologically active MPA in the liver cells.N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine, and the N-oxide portion of N-(2-hydroxyethyl)-morpholine are additional metabolites of MMF occurring in the intestine as a result of liver carboxylesterase 2 activity. UGT1A9 and UGT2B7 in the liver are the major enzymes contributing to the metabolism of MPA in addition to other UGT enzymes, which also play a role in MPA metabolism. The four major metabolites of MPA are 7-O-MPA-β-glucuronide (MPAG, inactive), MPA acyl-glucuronide (AcMPAG), produced by uridine 5ʹ-diphosphate glucuronosyltransferases (UGT) activities, 7-O-MPA glucoside produced via UGT, and small amounts 6-O-des-methyl-MPA (DM-MPA) via CYP3A4/5 and CYP2C8 enzymes.
Following oral and intravenous dosing, mycophenolate mofetil undergoes complete metabolism to MPA /mycophenolic acid/, the active metabolite. Metabolism to MPA occurs presystemically after oral dosing. MPA is metabolized principally by glucuronyl transferase to form the phenolic glucuronide of MPA (MPAG) which is not pharmacologically active. In vivo, MPAG is converted to MPA via enterohepatic recirculation. The following metabolites of the 2- hydroxyethyl-morpholino moiety are also recovered in the urine following oral administration of mycophenolate mofetil to healthy subjects: N-(2-carboxymethyl)-morpholine, N-(2- hydroxyethyl)-morpholine, and the N-oxide of N-(2-hydroxyethyl)-morpholine.

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Biological Half-Life
The average apparent half-life of mycophenolate mofetil is 17.9 (±6.5) hours after oral administration and 16.6 (±5.8) hours after intravenous administration.
For mycophenolic acid (MPA):Mean apparent: Approximately 17.9 hours after oral administration and 16.6 hours after intravenous administration.
Mean (+/-SD) apparent half-life and plasma clearance of MPA are 17.9 (+/-6.5) hours and 193 (+/-48) mL/min following oral administration and 16.6 (+/-5.8) hours and 177 (+/-31) mL/min following intravenous administration, respectively.

Protein Binding
The protein binding of mycophenolic acid, the metabolite of mycophenolate mofetil, is 97% and it is mainly bound to albumin. MPAG, the inactive metabolite, is 82% bound to plasma albumin at normal therapeutic concentrations. At elevated MPAG concentrations due to various reasons, including renal impairment, the binding of MPA may be decreased due to competition for binding.

[1]. Preliminary risk-benefit assessment of mycophenolate mofetil in transplant rejection. Drug Saf. 1997;17(2):75-92.

[2]. Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs. 1996;51(2):278-298.

Mycophenolate mofetil is a carboxylic ester resulting from the formal condensation between the carboxylic acid group of mycophenolic acid and the hydroxy group of 2-(morpholin-4-yl)ethanol. In the liver, it is metabolised to mycophenolic acid, an immunosuppressant for which it is a prodrug. It is widely used to prevent tissue rejection following organ transplants as well as for the treatment of certain autoimmune diseases. It has a role as an immunosuppressive agent, a prodrug, an EC 1.1.1.205 (IMP dehydrogenase) inhibitor and an anticoronaviral agent. It is a gamma-lactone, a member of phenols, an ether, a carboxylic ester and a tertiary amino compound. It is functionally related to a mycophenolic acid and a 2-(morpholin-4-yl)ethanol.
Mycophenolate mofetil, also known as MMF or CellCept, is a prodrug of mycophenolic acid, and classified as a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). This drug is an immunosuppressant combined with drugs such as [Cyclosporine] and corticosteroids to prevent organ rejection after hepatic, renal, and cardiac transplants. It is marketed by Roche Pharmaceuticals and was granted FDA approval for the prophylaxis of transplant rejection in 1995. In addition to the above uses, mycophenolate mofetil has also been studied for the treatment of nephritis and other complications of autoimmune diseases. Unlike another immunosuppressant class, the calcineurin inhibitors, MMF generally does not cause nephrotoxicity or fibrosis. Previously, mycophenolic acid (MPA) was administered to individuals with autoimmune diseases beginning in the 1970s, but was discontinued due to gastrointestinal effects and concerns over carcinogenicity. The new semi-synthetic 2-morpholinoethyl ester of MPA was synthesized to avoid the gastrointestinal effects associated with the administration of MPA. It demonstrates an increased bioavailability, a higher efficacy, and reduced gastrointestinal effects when compared to MPA.
Mycophenolate Mofetil is the morpholinoethyl ester of mycophenolic acid (MPA) with potent immunosuppressive properties. Mycophenolate stops T-cell and B-cell proliferation through selective inhibition of the de novo pathway of purine biosynthesis. In vivo, the active metabolite, MPA, reversibly inhibits inosine 5'-monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of guanine nucleotides. MPA displays high lymphocyte specificity and cytotoxicity due to the higher dependence of activated lymphocytes on both salvage and de novo synthesis of guanine nucleotides relative to other cell types. (NCI04)
Compound derived from Penicillium stoloniferum and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase (IMP DEHYDROGENASE). Mycophenolic acid exerts selective effects on the immune system in which it prevents the proliferation of T-CELLS, LYMPHOCYTES, and the formation of antibodies from B-CELLS. It may also inhibit recruitment of LEUKOCYTES to sites of INFLAMMATION.
See also: Mycophenolic Acid (has active moiety); Mycophenolate Mofetil Hydrochloride (has salt form).

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Drug Indication
Mycophenolate mofetil is indicated in combination with other immunosuppressants to prevent the rejection of kidney, heart, or liver transplants in adult and pediatric patients ≥3 months old. Mycophenolate mofetil may also be used off-label as a second-line treatment for autoimmune hepatitis that has not responded adequately to first-line therapy. Other off-label uses of this drug include lupus-associated nephritis and dermatitis in children.
FDA Label
CellCept is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.
Myfenax is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.
Myclausen is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants. ,
Mycophenolate mofetil Teva is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.

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Mechanism of Action
The active metabolite of mycophenolate, mycophenolic acid, prevents T-cell and B-cell proliferation and the production of cytotoxic T-cells and antibodies. Lymphocyte and monocyte adhesion to endothelial cells of blood vessels that normally part of inflammation is prevented via the glycosylation of cell adhesion molecules by MPA. MPA inhibits de novo purine biosynthesis (that promotes immune cell proliferation) by inhibiting inosine 5’-monophosphate dehydrogenase enzyme (IMPDH), with a preferential inhibition of IMPDH II. IMPDH normally transforms inosine monophosphate (IMP) to xanthine monophosphate (XMP), a metabolite contributing to the production of guanosine triphosphate (GTP). GTP is an important molecule for the synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein. As a result of the above cascade of effects, mycophenolate mofetil reduces de-novo production of guanosine nucleotides, interfering with the synthesis of DNA, RNA, and protein required for immune cell production. Further contributing to the above anti-inflammatory effects, MMF depletes tetrahydrobiopterin, causing the decreased function of inducible nitric oxide synthase enzyme, in turn decreasing the production of peroxynitrite, a molecule that promotes inflammation.
As a potent, selective, noncompetitive, and reversible, inhibitor of inosine monophosphate dehydrogenase (IMPDH), mycophenolic acid (MPA), the active metabolite /of mycophenolate mofetil/, inhibits the de novo synthesis pathway of guanosine nucleotides without being incorporated into DNA. Because T and B lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, while other cell types can utilize salvage pathways, MPA has potent cytostatic effects on lymphocytes. MPA inhibit proliferative responses of T and B lymphocytes to both mitogenic and allospecific stimulation. The addition of guanosine or deoxyguanosine reverses the cytostatic effects of MPA on lymphocytes. MPA also suppresses antibody formation by B lymphocytes. MPA prevents the glycosylation of lymphocytes and monocyte glycoproteins that are involved in intercellular adhesion of these cells to endothelial cells, and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection. Mycophenolate mofetil dose not inhibit the early events in the activation of human peripheral blood mononuclear cells, such as the production of interleukin-1 and interleukin-2, but does block the coupling of these events to DNA synthesis and proliferation.

C23H31NO7

433.4947

433.21

C, 63.73; H, 7.21; N, 3.23; O, 25.83

128794-94-5

Mycophenolate Mofetil-d4;1132748-21-0;Mycophenolate mofetil hydrochloride;116680-01-4

5281078

White to off-white solid powder

1.2±0.1 g/cm3

637.6±55.0 °C at 760 mmHg

95-96ºC

339.4±31.5 °C

0.0±2.0 mmHg at 25°C

1.557

3.15

94.53

1

8

10

31

646

0

O1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])OC(C([H])([H])C([H])([H])/C(/C([H])([H])[H])=C(\[H])/C([H])([H])C2C(=C3C(=O)OC([H])([H])C3=C(C([H])([H])[H])C=2OC([H])([H])[H])O[H])=O)C([H])([H])C1([H])[H]

RTGDFNSFWBGLEC-SYZQJQIISA-N

InChI=1S/C23H31NO7/c1-15(5-7-19(25)30-13-10-24-8-11-29-12-9-24)4-6-17-21(26)20-18(14-31-23(20)27)16(2)22(17)28-3/h4,26H,5-14H2,1-3H3/b15-4+

2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate

RS61443;Mycophenolic acid, Mycophenolate mofetil, Cellcept, Myfortic, RS-61443;Mycophenolate mofetil (free acid);

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 0.5% methylcellulose:20 mg/mL

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配方 5 中的溶解度: 33.33 mg/mL (76.89 mM) in Cremophor EL (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。