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Tacrolimus monohydrate

PubChem CID
5282315
Structure
Tacrolimus monohydrate_small.png
Molecular Formula
Synonyms
  • TACROLIMUS MONOHYDRATE
  • Tacrolimus hydrate
  • 109581-93-3
  • Prograf
  • Protopic
Molecular Weight
822.0 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-18
Description
Tacrolimus hydrate is a hydrate that is the monohydrate form of tacrolimus. It has a role as an immunosuppressive agent. It contains a tacrolimus (anhydrous).
TACROLIMUS is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 1994 and has 3 approved indications. This drug has a black box warning from the FDA.
A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
See also: Tacrolimus (annotation moved to).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Tacrolimus monohydrate.png

1.2 3D Status

Conformer generation is disallowed since too many atoms, mixture or salt

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-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;hydrate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C44H69NO12.H2O/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7;/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3;1H2/b25-19+,27-21+;/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+;/m0./s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

NWJQLQGQZSIBAF-MLAUYUEBSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C[C@@H]1C[C@@H]([C@@H]2[C@H](C[C@H]([C@@](O2)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@@H]([C@@H]([C@H](CC(=O)[C@@H](/C=C(/C1)\C)CC=C)O)C)/C(=C/[C@@H]4CC[C@H]([C@@H](C4)OC)O)/C)O)C)OC)OC.O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C44H71NO13
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 KEGG ID

2.3.8 Metabolomics Workbench ID

2.3.9 Wikidata

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Anhydrous Tacrolimus
  • Anhydrous, Tacrolimus
  • FK 506
  • FK-506
  • FK506
  • FR 900506
  • FR-900506
  • FR900506
  • Prograf
  • Prograft
  • Tacrolimus
  • Tacrolimus Anhydrous
  • Tacrolimus, Anhydrous

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
822.0 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
13
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
7
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
821.49254132 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
821.49254132 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
179 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
58
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
1480
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
14
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
2
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
2
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Chemical Classes

3.2.1 Drugs

3.2.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Immunosuppressive Agents; Dermatologic Agents

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug Indication

6.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Immunosuppressive Agents; Dermatologic Agents

6.3 Clinical Trials

6.3.1 ClinicalTrials.gov

6.3.2 EU Clinical Trials Register

6.3.3 NIPH Clinical Trials Search of Japan

7 Pharmacology and Biochemistry

7.1 MeSH Pharmacological Classification

Calcineurin Inhibitors
Compounds that inhibit or block the PHOSPHATASE activity of CALCINEURIN. (See all compounds classified as Calcineurin Inhibitors.)
Immunosuppressive Agents
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. (See all compounds classified as Immunosuppressive Agents.)

8 Safety and Hazards

8.1 Hazards Identification

8.1.1 GHS Classification

Pictogram(s)
Acute Toxic
Signal
Danger
GHS Hazard Statements
H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]
Precautionary Statement Codes

P264, P270, P301+P316, P321, P330, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 115 reports by companies from 9 notifications to the ECHA C&L Inventory.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

8.1.2 Hazard Classes and Categories

Acute Tox. 3 (100%)

9 Toxicity

9.1 Toxicological Information

9.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Limited data indicate that amounts of systemically administered tacrolimus are low in breastmilk and probably do not adversely affect the breastfed infant. United States and European experts and guidelines consider tacrolimus to be probably safe to use during breastfeeding. Exclusively breastfed infants should be monitored if this drug is used during lactation, possibly including measurement of serum levels to rule out toxicity if there is a concern.

Topical tacrolimus presents a low risk to the nursing infant because it is poorly absorbed after topical application and peak blood concentrations are less than 2 mcg/L in most patients. Ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Current guidelines allow topical tacrolimus to be applied to the nipples just after nursing, with the nipples cleaned gently before nursing. Only water-miscible cream or gel products should be applied to the breast or nipple because ointments may expose the infant to high levels of mineral paraffins via licking, so pimecrolimus cream may be preferable to tacrolimus ointment for nipple application.

◉ Effects in Breastfed Infants

One infant was exclusively breastfed during maternal tacrolimus therapy throughout gestation to at least 2.5 months of age at which time the infant was developing normally physically and neurologically. An ultrasound examination of the infant's thymus was normal.

The National Transplantation Pregnancy Registry reported data gathered from 1991 to 2011 on mothers who breastfed their infants following organ transplantation. A total of 68 mothers with transplants (mostly kidney or liver) used tacrolimus while breastfeeding a total of 83 infants. Duration of nursing ranged from 1 week to 1.5 years and follow-up of the children ranged from weeks to 16 years. There were no reports of problems in any of the infants or children. As of December 2013, a total of 92 mothers had breastfed 125 infants for as long as 26 months with no apparent adverse effects in infants.

The breastfed infants of six women who took tacrolimus during pregnancy for organ transplantation were breastfed (4 exclusive, 2 partial) for 45 to 180 days and followed for periods of 2 to 30 months. The mothers' mean daily tacrolimus dosage during breastfeeding was 9.6 mg daily (range 4.5 to 15 mg daily). Four mothers were also taking azathioprine 100 to 150 mg daily, one was taking diltiazem, and one was taking prednisolone 15 mg and aspirin 75 mg daily. None of the infants had any clear tacrolimus-related side effects, although one had transient thrombocytosis that resolved despite continued breastfeeding. Developmental milestones were normal and no pattern of infections was noted.

Two mothers with systemic lupus erythematosus were reported who took tacrolimus 3 mg daily during pregnancy and lactation as well as prednisolone 30 or 40 mg daily. Three years after birth, both children were healthy. The durations of lactation were not stated.

In a case series of women who had liver transplants over a 25-year period, one woman breastfed (extent not stated) her infant while taking tacrolimus. No neonatal complications were noted.

A mother with a liver transplant was maintained on belatacept 10 mg/kg monthly, slow-release tacrolimus (Envarsus and Veloxis) 2 mg daily, azathioprine 25 mg daily, and prednisone 2.5 mg daily. She breastfed her infant for a year (extent not stated). The infant’s growth and cognitive milestones were normal.

An Australian case series reported 3 women with heart transplants who had a total of 5 infants, all of whom were breastfed (extent not stated) during maternal tacrolimus therapy. Daily dosages ranged from 3 to 13 mg daily. No adverse infant effects were reported up to the times of discharge.

A woman with rheumatoid arthritis refractory to etanercept took sarilumab 200 mg every two weeks during pregnancy until 37 weeks of gestation. She was also taking prednisolone 10 mg and tacrolimus 3 mg daily. She delivered a healthy infant at 38 weeks of gestation and breastfed her infant. Prednisolone was continued postpartum, tacrolimus was restarted at 7 days postpartum, and sarilumab was restarted at 28 days postpartum. The mother continued to breastfeed until 6 months postpartum. The infant was vaccinated with multiple live vaccines after reaching six months old, including the Bacille-Calmette-Guerin vaccine, with no adverse effects.

A woman with a heart transplant took tacrolimus alone throughout pregnancy and postpartum while breastfeeding her infant (extent not stated) for one year. The child had normal weight gain, normal motor development, and no signs of metabolic disorders or significant infections. The age of the infant at evaluation was not stated.

◉ Effects on Lactation and Breastmilk

A study in renal transplant patients who were on a tacrolimus-based immunosuppression regimen found that women’s median serum prolactin levels were 14.4 mcg/L compared with women who were not taking tacrolimus (17.6 mcg/L). The difference was statistically significant. Median serum testosterone levels (0.121 vs 0.137 mcg/L) and serum cortisol levels (82.5 vs 105 mg/L) were also significantly lower in the tacrolimus group. The reduced prolactin may be caused by inhibition of the transcription of the human prolactin gene. Not all studies have found a reduction in serum prolactin with tacrolimus. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

9.1.2 Acute Effects

10 Associated Disorders and Diseases

11 Literature

11.1 Consolidated References

11.2 NLM Curated PubMed Citations

11.3 Springer Nature References

11.4 Chemical Co-Occurrences in Literature

11.5 Chemical-Gene Co-Occurrences in Literature

11.6 Chemical-Disease Co-Occurrences in Literature

12 Patents

12.1 Depositor-Supplied Patent Identifiers

12.2 WIPO PATENTSCOPE

12.3 Chemical Co-Occurrences in Patents

12.4 Chemical-Disease Co-Occurrences in Patents

12.5 Chemical-Gene Co-Occurrences in Patents

13 Interactions and Pathways

13.1 Chemical-Target Interactions

14 Biological Test Results

14.1 BioAssay Results

15 Classification

15.1 MeSH Tree

15.2 NCI Thesaurus Tree

15.3 ChEBI Ontology

15.4 KEGG: Drug

15.5 KEGG: USP

15.6 KEGG: ATC

15.7 KEGG: Target-based Classification of Drugs

15.8 KEGG: JP15

15.9 KEGG: Drug Groups

15.10 KEGG: Drug Classes

15.11 ChemIDplus

15.12 UN GHS Classification

15.13 MolGenie Organic Chemistry Ontology

16 Information Sources

  1. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    15,19-Epoxy-3H-pyrido(2,1-C)-(1,4)oxaazacyclotricosine-1,7,20,21- (4H,23H)-tetrone, 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a -hexadecahydro-5,19-dihydroxy-3-(2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl)-14,16-dimethoxy-4,10,12,18-tetramethyl-8- (2-propenyl)-, monohydrate,(3S-(3R*,(E(1S*,3S*,4S*)),4S*,5R*,8S*, 9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*))-
    https://echa.europa.eu/substance-information/-/substanceinfo/100.162.529
    15,19-Epoxy-3H-pyrido(2,1-C)-(1,4)oxaazacyclotricosine-1,7,20,21- (4H,23H)-tetrone, 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a -hexadecahydro-5,19-dihydroxy-3-(2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl)-14,16-dimethoxy-4,10,12,18-tetramethyl-8- (2-propenyl)-, monohydrate,(3S-(3R*,(E(1S*,3S*,4S*)),4S*,5R*,8S*, 9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*))- (EC: 634-559-2)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/167350
  4. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  5. ChEBI
  6. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  7. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  8. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  9. Drugs and Lactation Database (LactMed)
  10. EU Clinical Trials Register
  11. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
  12. Metabolomics Workbench
  13. NIPH Clinical Trials Search of Japan
  14. Springer Nature
  15. Wikidata
  16. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  17. PubChem
  18. GHS Classification (UNECE)
  19. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  20. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  21. PATENTSCOPE (WIPO)
CONTENTS