Tacrolimus
FK-506 · prograf · Protopic · Advagraf · Tacrolimus premix · Tacrolimus reference · imus) · Tacros
Identifiers & Physical Properties
| CAS No. | 104987-11-3 |
|---|---|
| Molecular formula | C44H69NO12 |
| Average molar mass | 804 g/mol |
| Monoisotopic mass | 803.48197665 g/mol |
| SMILES | C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC |
| InChIKey | QJJXYPPXXYFBGM-LFZNUXCKSA-N |
| PubChem CID | 445643 |
| ChEMBL | CHEMBL269732 |
| ChEBI | CHEBI:61049 |
| EC No. | 627-021-3 |
| DTXSID | DTXSID5046354 |
Chemical & Physical Properties
| XLogP | 2.7 |
|---|---|
| Topological polar surface area | 178 |
| Hydrogen bond donors | 3 |
| Hydrogen bond acceptors | 12 |
| Rotatable bonds | 7 |
| Heavy atoms | 57 |
| Formal charge | 0 |
| Complexity | 1,480 |
| Lipids | Polyketides [PK] -> Macrolides and lactone polyketides [PK04] |
| Solubility | InsolubleDMSO: >3 mg/mLFreely soluble in DMSO or ethanol. Poorly soluble in water.Soluble in dimethyl sulfoxide, ethanol, water, acetone, chloroform, ethyl acetate, ether, methanol and dimethyl formamide. |
| Human Drugs | Breast FeedingLactationMilk, HumanImmunosuppressive AgentsDermatologic AgentsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine |
| Optical Rotation | Colorless prisms from acetonitrilemp 127-129 °C. Specific optical rotation: -84.4 deg at 23 °C/D (c = 1.02 in chloroform). Soluble in methanol, ethanol, acetone, ethyl acetate, chloroform, diethyl ethersparingly soluble in hexane, petroleum ether. Insoluble in water. /Tacrolimus monohydrate/ |
| Stability/Shelf Life | Stable under recommended storage conditions. /FK-506 monohydrate/ |
| Collision Cross Section | 267 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]269.55 Ų [M+Na]+ [CCS Type: TW |
| Melting point | 113-115°C |
| Boiling point | 871.7±75.0 °C(Predicted) |
| Density | 1.19±0.1 g/cm3(Predicted) |
| Flash point | 2℃ |
| Storage conditions | Sealed in dry,Store in freezer, under -20°C |
| Physical state | solid |
| pKa (acidity coefficient) | 9.97±0.70(Predicted) |
| Color | white |
| optical activity | +62.223 (CHCl3) |
| BCS Class | 2 |
| Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 2 months. |
| InChIKey | QJJXYPPXXYFBGM-LFZNUXCKSA-N |
| CAS DataBase Reference | 104987-11-3(CAS DataBase Reference) |
| NCI Dictionary of Cancer Terms | tacrolimus |
| FDA UNII | Y5L2157C4J |
| NCI Drug Dictionary | Prograf |
| ATC code | D11AH01,L04AD02 |
| UNSPSC Code | 41116107 |
| NACRES | NA.77 |
| Protein binding | >98% |
| Excreted unchanged in urine | <1% |
| Volume of distribution | 1300 Litres |
| Biological half-life | 12-16 / Probably unchanged |
| GHS pictogram | GHS06,GHS08 |
| Signal word | Danger |
| GHS hazard statements | H301-H361f-H373 |
| GHS precautionary statements | P202-P260-P264-P270-P280-P301+P310 |
| Hazard symbols | T,Xi,Xn,F |
| Risk statements (R) | 25-36/37/38-36-20/21/22-11 |
| Safety statements (S) | 45-36-26-36/37-16-60-20 |
| UN transport number | UN 2811 6.1/PG 3 |
| Water hazard class (WGK) | 3 |
| RTECS number | KD4201200 |
| Hazard class | 6.1Acute Tox. 3 OralEye Irrit. 2Repr. 2STOT RE 2 |
| Customs code | 29349990 |
| Storage class | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Hazardous substances data | 104987-11-3(Hazardous Substances Data) |
Safety & Regulations
| GHS classification | DangerH301 (97.6%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P260, P264, P270, P280, P301+P316, P318, P319, P321, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 82 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral] |
|---|---|
| Regulatory information | Hazard Traits - Carcinogenicity |
| FDA requirements | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including tacrolimus, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx). /FK-506 monohydrate/ |
| Hazard Classes and Categories | Acute Tox. 3 (100%)Acute Tox. 3 (97.6%) |
| Hazardous Reactivities and Incompatibilities | Strong oxidizing agents. /FK-506 monohydrate/ |
| Fire fighting procedures | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /FK-506 monohydrate/ |
| Storage conditions | Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: -20 °C Keep in a dry place. /FK-506 monohydrate/Store at 25 °C (77 °F)excursions permitted to 15 °C-30 °C (59 °F-86 °F).Store at room temperature 25 °C (77 °F)excursions permitted to 15 deg - 30 °C (59 deg - 86 °F). |
| Cleanup methods | Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /FK-506 monohydrate/ |
Applications & Uses
Description
Tacrolimus, isolated from the microorganism Streptomyces tsukubaensis, is a macrolide immunosuppressant developed by Fujisawa for organ transplantation. It displays similar but more potent immunosuppressive activity than cyclosporin. It inhibits both cell mediated and humoral immune responses. In animal models of organ transplantation, tacrolimus has been shown to prolong survival of hepatic, renal, cardiac, small intestine, pancreatic and skin allografts and to reverse cardiac and renal allograft rejection. It has been used effectively in humans as rescue or primary immunosuppressant therapy in liver or kidney transplantation. Compared to cyclosporin, tacrolimus causes reduced incidence of infectious complications and of hypertension and hypercholesterolemia for the allograft recipients. In common with cyclosporin, tacrolimus binds with high affinity to a family of cytoplasmic immunosuppressant binding proteins, the immunophilins. This tight complex is proposed as the biologically active moiety that interacts with intracellular molecules involved in signal transduction.It inhibits phosphatase activity of calcineurin, an action that may impair the generation and/or activation of nuclear transcription factors required for lymphokine (particularly interleukin-2) gene expression. Tacrolimus has also been reported to have potential in multiple sclerosis, psoriasis, rheumatoid arthritis and uveitis associated with Behcet‘s disease.
Description
FK-506 is a potent immunosuppressant in the same molecular class as cyclosporin A and rapamycin . Its mechanism of action involves the formation of a high affinity complex (Ki = 0.2 nM) with FK-506 binding protein 12 (FKBP12). This complex then inhibits the activity of the calcium/calmodulin-dependent protein phosphatase, calcineurin, leading to disruption of T cell activation. The physiological effects of FK-506 also include regulation of nitric oxide neurotoxicity, neurotransmitter release, and regulation of Ca2+ release via the ryanodine and inositol-(1,4,5)-trisphosphate (IP3) receptors. In the latter case, FKBP12 forms a tight complex with both ryanodine and IP3 receptors which can be disrupted by FK-506, thereby rendering the receptors leaky to Ca2+.
Uses
FK-506 (Tacrolimus) is a macrolide immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system
Uses
Tacrolimus (fujimycin) was discovered as a potent inhibitor of IL2 production in a targeted search for novel immunosuppressants. Tacrolimus acts by blocking T cell proliferation in vitro by inhibiting the generation of several lymphokines, notably the original target IL-2. Tacrolimus inhibits the activity of FK-506 binding protein, Ca2+-dependent phosphatase and calcineurin, and activates NF-κB through phosphorylation and degradation of IκBα.