13-Demethyl tacrolimus

A summary of the most common chemical descriptors (InChI Key and SMILES codes) for 13-Demethyl tacrolimus are summarized together with 3D and 2D structures and relevant physico-chemical properties.

What is the 13-Demethyl tacrolimus?

The molecule 13-Demethyl tacrolimus presents a molecular formula of C₄₃H₆₇NO₁₂ and its IUPAC name is (1R,9S,12S,13R,14S,17R,18Z,21S,23S,24S,25S,27R)-1,14,25-trihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23-methoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone.

Tacrolimus (FK506) is an immunosuppressive drug used mainly after allogeneic organ transplant to lower the risk of organ rejection. It is also used in a topical form in the treatment of eczema, particularly atopic dermatitis, lichen planus, and seborrheic dermatitis. Tacrolimus was discovered in 1984 from the soil bacterium Streptomyces tsukubaensis..

Tacrolimus acts by binding to an intracellular protein, FKBP12. This binding inhibits calcineurin, which is a calcium-dependent phosphatase. Inhibiting calcineurin prevents dephosphorylation of the transcription factors NFATc2 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2) and AP-1 (activator protein 1). The binding of tacrolimus to FKBP12 also alters the conformation of the FKBP12-calcineurin-NFATc2 complex, which prevents the complex from translocating to the nucleus and thus inhibits transcription of genes involved in the immune response..

The main side effects of tacrolimus are nephrotoxicity, neurotoxicity, and gastrointestinal toxicity. Other side effects include hypertension, diabetes, and skin cancer..

Tacrolimus is a macrolide immunosuppressive agent produced by Streptomyces tsukubaensis.1 It has a molecular weight of 804.52 and the following chemical structure:.

Tacrolimus exists as 0.5 mg, 1 mg, and 5 mg capsules and as a 1% ointment..

The recommended dose of tacrolimus for immunosuppression in adults is 0.1 to 0.15 mg/kg/day given orally in two or three divided doses. The dose may be increased or decreased based on the patient’s response..

The recommended dose of tacrolimus for the treatment of eczema is 0.03% to 0.1% ointment applied topically to the affected area once or twice daily..

Tacrolimus is contraindicated in patients with a history of hypersensitivity to tacrolimus or any of the other ingredients in the formulation..

Tacrolimus should be used with caution in patients with renal impairment, hypertension, diabetes, or a history of skin cancer..

Tacrolimus may interact with other drugs, such as cyclosporine, aminoglycosides, and macrolide antibiotics..

Tacrolimus is a pregnancy category C drug. Animal studies have shown an increased risk of birth defects with tacrolimus, but there are no adequate and well-controlled studies in humans. Tacrolimus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus..

Tacrolimus is excreted in human milk. Women who are taking tacrolimus should not breastfeed..

The most common side effects of tacrolimus are nephrotoxicity, neurotoxicity, and gastrointestinal toxicity. Other side effects include hypertension, diabetes, and skin cancer..

Tacrolimus is a potent immunosuppressive agent that is used mainly after allogeneic organ transplant to lower the risk of organ rejection. It is also used in a topical form to treat eczema. Tacrolimus acts by binding to an intracellular protein, FKBP12, which inhibits calcineurin. Inhibiting calcineurin prevents dephosphorylation of the transcription factors NFATc2 and AP-1. The binding of tacrolimus to FKBP12 also alters the conformation of the FKBP12-calcineurin-NFATc2 complex, which prevents the complex from translocating to the nucleus and thus inhibits transcription of genes involved in the immune response. The main side effects of tacrolimus are nephrotoxicity, neurotoxicity, and gastrointestinal toxicity. Other side effects include hypertension, diabetes, and skin cancer..

3D structure

Cartesian coordinates

Geometry of 13-Demethyl tacrolimus in x, y and z coordinates (Å units) to copy/paste elsewhere. Generated with Open Babel software.

2D drawing

Molecule descriptors

Other names (synonyms)

IUPAC nomenclature provides a standardized method for naming chemical compounds. Although this system is widely used in chemistry, many chemical compounds have also other names commonly used in different contexts. These synonyms can come from a variety of sources and are used for a variety of purposes.

One common source of synonyms for chemical compounds is the common or trivial names, assigned on the basis of appearance, properties, or origin of the molecule.

Another source of synonyms are historical or obsolete names employed in the past, however replaced nowadays by more modern or standardized names.

In addition to common and historical names, chemical compounds may also have synonyms that are specific to a particular field or industry.

Reference codes for other databases

• CAS number (Chemical Abstracts Service Registry Number) is a unique identifier is assigned to every chemical compound indexed in the CAS database.
• Beilstein: The Beilstein database is a comprehensive source of information on organic chemistry, including information on chemical structures, properties, and reactions. The Beilstein database assigns unique identifiers which can be used to identify compounds in scientific literature and other sources.
• ChEBI (Chemical Entities of Biological Interest): ChEBI is a database of small chemical molecules that are of interest in the field of biology.
• PubChem CID (Compound Identifier): PubChem is a database of chemical compounds that is maintained by the National Institutes of Health (NIH).
• RTECS number (Registry of Toxic Effects of Chemical Substances): The RTECS is a database of information on the toxic effects of chemicals, including information on their structures and properties.
• ChEMBL (Compound Bioactivity Data): ChEMBL is a database of bioactivity data for small molecules, including information on their properties and structures.
• CompTox Dashboard (Environmental Protection Agency): The CompTox Dashboard is a database of information on the toxicology and environmental effects of chemicals.

Physico-Chemical properties

LogP and topological polar surface area (TPSA) values were estimated using Open Babel software.

The n-octanol/water partition coeficient (K_ow) data is applied in toxicology and drug research. K_ow values are used, to guess the environmental fate of persistent organic pollutants. High partition coefficients values, tend to accumulate in the fatty tissue of organisms. Molecules with a log(K_ow) (or LogP) greater than 5 are considered to bioaccumulate.

TPSA values are the sum of the surface area over all polar atoms or molecules, mainly oxygen and nitrogen, also including hydrogen atoms.

In medicinal chemistry, TPSA is used to assess the ability of a drug to permeabilise cells.

For molecules to penetrate the blood-brain barrier (and act on receptors in the central nervous system), TPSA values below 90 Ų are required. Thus, molecules with a polar surface area greater than 140 Ų tend to be poorly permeable to cell membranes.