| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
Umirolimus targets the mTOR kinase, specifically mTORC1, by binding to FKBP12, forming a complex that inhibits mTOR signaling. This leads to suppression of cytokine-driven T cell proliferation and inhibition of smooth muscle cell migration and proliferation, which is critical for preventing neointimal hyperplasia in vascular stents. It also has anti-inflammatory effects by reducing the release of pro-inflammatory cytokines.
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|---|---|
| ln Vitro |
The pharmacological characteristics of the macrocyclic trienolide umirolimus were specially designed for topical medication administration. Applications involving drug-eluting stents (DES) can make advantage of umilolimus. It contributes to cellular absorption and sustained dispersion in the vessel wall surrounding the stent because of its increased lipophilicity, which makes it strongly attracted to binding sites within vessel walls and small, tortuous vessels [1]. Umirolimus inhibits the activation of P70-KD S6 protein kinase mediated by IL-2/mTOR, hence blocking the progression of the G1 cell cycle. Both smooth muscle cell and T cell proliferation are inhibited by ummirolimus [1].
In vitro, umirolimus is a potent inhibitor of T cell proliferation with an IC50 in the low nanomolar range (approximately 0.1 nM). It also inhibits the proliferation of vascular smooth muscle cells and endothelial cells. Umirolimus shows higher anti-proliferative activity compared to sirolimus and everolimus in some assays. It binds to FKBP12 with high affinity and effectively inhibits mTOR kinase activity in cell-free assays. Its lipophilicity (logP ≈ 5.5) promotes rapid cellular uptake. |
| ln Vivo |
Umirolimus has an approximately 25-hour elimination half-life in whole blood [1].
In vivo, umirolimus has been extensively studied in drug-eluting stents. In porcine and rabbit models of coronary restenosis, umirolimus-eluting stents significantly reduce neointimal formation and lumen stenosis compared to bare-metal stents. The compound's prolonged tissue retention due to its lipophilicity provides sustained efficacy over weeks. In transplantation models, umirolimus shows immunosuppressive activity similar to sirolimus, prolonging graft survival. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for umirolimus include FKBP12 binding assays using fluorescence polarization or competition with radiolabeled FK506. mTOR kinase activity is measured using recombinant mTOR and a substrate, with ATP consumption quantified. The IC50 for mTOR inhibition is determined. Cellular proliferation assays use T cells or smooth muscle cells, with [3H]thymidine incorporation or MTT to measure IC50 values.
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| Cell Assay |
In vitro cellular assays for umirolimus are performed using primary human T cells or smooth muscle cells. Cells are treated with umirolimus and stimulated with mitogens (e.g., PHA or IL-2). Proliferation is measured by BrdU incorporation or MTT. Cytokine production (e.g., IL-2, IFN-γ) is measured by ELISA. Flow cytometry is used to assess cell cycle arrest at G1 phase. For smooth muscle cells, migration and proliferation are assessed by wound healing and proliferation assays.
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| Animal Protocol |
In vivo animal experiments for umirolimus are conducted in porcine coronary models, where drug-eluting stents are implanted, and angiography and histology are performed at follow-up to assess neointimal thickness and lumen area. Immunosuppressive efficacy is evaluated in rodent allograft models, such as skin or heart transplantation, where umirolimus is administered orally or intraperitoneally, and graft survival is monitored. Pharmacokinetic studies measure tissue and plasma concentrations.
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| ADME/Pharmacokinetics |
Umirolimus has a molecular weight of 985.34 g/mol and a molecular formula of C55H87NO12. It is a white to off-white powder, highly lipophilic, practically insoluble in water, but soluble in organic solvents such as ethanol and DMSO. Its high lipophilicity enhances tissue affinity and prolonged retention. Pharmacokinetics in humans show a long half-life (days) in tissue, but plasma levels are low. It is metabolized by CYP3A4 and excreted primarily in feces.
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| Toxicity/Toxicokinetics |
Umirolimus has a safety profile similar to other mTOR inhibitors. Common adverse effects include hypertension, hyperlipidemia, and myelosuppression. In stent applications, systemic exposure is minimal, reducing systemic side effects. However, in transplantation studies, it shows dose-limiting toxicity at high doses. Preclinical toxicity studies indicate effects on the gastrointestinal tract, liver, and bone marrow, but these are reversible upon dose reduction.
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| References |
[1]. Eberhard Grube, et al. BioMatrix Biolimus A9-eluting coronary stent: a next-generation drug-eluting stent for coronary artery disease. Expert Rev Med Devices. 2006 Nov;3(6):731-41.
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| Additional Infomation |
Umirolimus is a sirolimus derivative used primarily in drug-eluting stents, marketed as BioMatrix and Nobori. It was developed by Biosensors International. Its high lipophilicity allows for rapid and sustained drug delivery from polymer coatings, reducing restenosis rates in coronary interventions. Umirolimus is not approved for systemic immunosuppression but is under investigation for other indications. Its mechanism is identical to that of sirolimus, but its pharmacokinetic properties offer advantages in local delivery.
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| Molecular Formula |
C55H87NO14
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|---|---|
| Molecular Weight |
986.29
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| Exact Mass |
985.612
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| CAS # |
851536-75-9
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| PubChem CID |
11158972
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
991.0±75.0 °C at 760 mmHg
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| Flash Point |
553.1±37.1 °C
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| Vapour Pressure |
0.0±0.6 mmHg at 25°C
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| Index of Refraction |
1.540
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| LogP |
4.24
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
70
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| Complexity |
1840
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| Defined Atom Stereocenter Count |
15
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| SMILES |
CCOCCO[C@@]1([H])[C@]([H])(OC)C[C@]([H])(C[C@]([H])([C@@]2([H])OC(=O)[C@@]3([H])N(C(=O)C(=O)[C@@]4(O[C@]([H])(C[C@]([H])(OC)C(=C([H])C([H])=C([H])C([H])=C([H])[C@]([H])(C[C@]([H])(C(=O)[C@]([H])(OC)[C@]([H])(O)C(=C([H])[C@]([H])(C(=O)C2)C)C)C)C)C)CC[C@@]4([H])C)O)CCCC3)C)CC1 |c:43,64,t:39,47|
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| InChi Key |
YYSFXUWWPNHNAZ-PKJQJFMNSA-N
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| InChi Code |
InChI=1S/C55H87NO14/c1-12-67-26-27-68-45-24-22-41(31-48(45)65-10)30-37(5)47-33-44(57)36(4)29-39(7)50(59)51(66-11)49(58)38(6)28-34(2)18-14-13-15-19-35(3)46(64-9)32-42-23-21-40(8)55(63,70-42)52(60)53(61)56-25-17-16-20-43(56)54(62)69-47/h13-15,18-19,29,34,36-38,40-43,45-48,50-51,59,63H,12,16-17,20-28,30-33H2,1-11H3/b15-13+,18-14+,35-19+,39-29+/t34-,36-,37-,38-,40-,41+,42+,43+,45-,46+,47+,48-,50-,51+,55-/m1/s1
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| Chemical Name |
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-12-[(2R)-1-[(1S,3R,4R)-4-(2-ethoxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
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| Synonyms |
TRM-986; TRM 986; Umirolimus
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~101.39 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (5.07 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.53 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0139 mL | 5.0695 mL | 10.1390 mL | |
| 5 mM | 0.2028 mL | 1.0139 mL | 2.0278 mL | |
| 10 mM | 0.1014 mL | 0.5070 mL | 1.0139 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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