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Identification
Name Pimecrolimus
Accession Number DB00337 (APRD01182)
Type small molecule
Groups approved
Description

Pimecrolimus is an immunomodulating agent used in the treatment of atopic dermatitis (eczema). It is currently available as a topical cream, once marketed by Novartis, (however Galderma will be promoting the molecule in Canada in early 2007) under the trade name Elidel. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • ASM 981
  • SDZ ASM 981
Synonyms
ASM 981
SDZ ASM 981
Salts Not Available
Brand names
Name Company
Elidel
Brand mixtures Not Available
Categories
  • Enzyme Inhibitors
  • Dermatologic Agents
  • Immunosuppressive Agents
CAS number 137071-32-0
Weight Average: 810.453
Monoisotopic: 809.44808973
Chemical Formula C43H68ClNO11
InChI Key InChIKey=KASDHRXLYQOAKZ-UURIOSKDSA-N
InChI
InChI=1S/C43H68ClNO11/c1-10-30-18-24(2)17-25(3)19-36(53-8)39-37(54-9)21-27(5)43(51,56-39)40(48)41(49)45-16-12-11-13-32(45)42(50)55-38(28(6)33(46)23-34(30)47)26(4)20-29-14-15-31(44)35(22-29)52-7/h18,20,25,27-33,35-39,46,51H,10-17,19,21-23H2,1-9H3/b24-18+,26-20+/t25-,27+,28-,29-,30+,31-,32-,33-,35+,36-,37-,38+,39+,43+/m0/s1
Plain Text
IUPAC Name
(1R,9S,12S,13S,14S,17R,18Z,21S,23S,24R,25S,27R)-12-[(1E)-1-[(1R,3R,4S)-4-chloro-3-methoxycyclohexyl]prop-1-en-2-yl]-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^{4,9}]octacos-18-ene-2,3,10,16-tetrone
SMILES
CC[C@@H]1\C=C(C)/C[C@H](C)C[C@H](OC)[C@H]2O[C@](O)([C@H](C)C[C@@H]2OC)C(=O)C(=O)N2CCCC[C@H]2C(=O)O[C@@H]([C@@H](C)[C@@H](O)CC1=O)C(\C)=C\[C@@H]1CC[C@H](Cl)[C@@H](C1)OC
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Glycerol and Derivatives
  • Pyrans
  • Lactams
  • Piperidines
  • Macrolides
Substructures
  • Carboxylic Acids and Derivatives
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Pyrans
  • Acetates
  • Lactones
  • Amino Ketones
  • Acetals and Derivatives
  • Ethers
  • Aliphatic and Aryl Amines
  • Alkyl Halides
  • Heterocyclic compounds
  • Carboxamides and Derivatives
  • Lactams
  • Alcohols and Polyols
  • Piperidines
  • Ketones
  • Macrolides
Pharmacology
Indication For treatment of mild to moderate atopic dermatitis.
Pharmacodynamics Pimecrolimus is a chemical that is used to treat atopic dermatitis (eczema). Atopic dermatitis is a skin condition characterized by redness, itching, scaling and inflammation of the skin. The cause of atopic dermatitis is not known; however, scientists believe that it may be due to activation of the immune system by various environmental or emotional triggers. Scientists do not know exactly how pimecrolimus reduces the manifestations of atopic dermatitis, but pimecrolimus reduces the action of T-cells and mast cells which are part of the immune system and contribute to responses of the immune system. Pimecrolimus prevents the activation of T-cells by blocking the effects of chemicals (cytokines) released by the body that stimulate T-cells. Pimecrolimus also reduces the ability of mast cells to release chemicals that promote inflammation.
Mechanism of action Pimecrolimus binds with high affinity to macrophilin-12 (FKBP-12) and inhibits the calcium-dependent phosphatase, calcineurin. As a consequence, it inhibits T cell activation by blocking the transcription of early cytokines. In particular, pimecrolimus inhibits at nanomolar concentrations Interleukin-2 and interferon gamma (Th1-type) and Interleukin-4 and Interleukin-10 (Th2-type) cytokine synthesis in human T cells. Also, pimecrolimus prevents the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/lgE.
Absorption Because of the low systemic absorption of pimecrolimus following topical application the calculation of standard pharmacokinetic measures such as AUC, Cmax, half-life, etc. cannot be reliably done.
Volume of distribution Not Available
Protein binding 74%-87% (in vitro, bound to plasma proteins)
Metabolism No drug metabolism was observed in human skin in vitro. Oral administration yielded metabolites produced from O-demethylation and oxygenation reactions.
Route of elimination 80% of the drug is excreted in the feces.
Half life Not Available
Clearance Not Available
Toxicity Side effects include burning sensation, irritation, pruritus, erythema, and skin infections, at the application site.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Cream Topical
Prices
Unit description Cost Unit
Elidel 100 Gram Tube 1% 100 gm Tube 315.76 USD tube
Elidel 60 Gram Tube 1% 60 gm Tube 200.05 USD tube
Elidel 30 Gram Tube 1% 30 gm Tube 101.44 USD tube
Elidel 1% cream 3.21 USD g
Patents
Country Patent Number Approved Expires (estimated)
United States 6423722 1998-12-26 2018-12-26
United States 6352998 1995-10-26 2015-10-26
Canada 2200966 2006-12-19 2015-10-26
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 4.4 PhysProp
Predicted Properties
Property Value Source
water solubility 1.52e-03 g/l ALOGPS
logP 4.36 ALOGPS
logP 6.81 ChemAxon Molconvert
logS -5.7 ALOGPS
pKa 14.66 ChemAxon Molconvert
hydrogen acceptor count 10 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 158.13 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 214.03 ChemAxon Molconvert
polarizability 87.87 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Grassberger M, Baumruker T, Enz A, Hiestand P, Hultsch T, Kalthoff F, Schuler W, Schulz M, Werner FJ, Winiski A, Wolff B, Zenke G: A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol. 1999 Aug;141(2):264-73. Pubmed
External Links
Resource Link
PubChem Compound 17753757 Link_out
PubChem Substance 46505748 Link_out
Therapeutic Targets Database DAP000594 Link_out
PharmGKB PA10157 Link_out
Drug Product Database 2247238 Link_out
RxList http://www.rxlist.com/cgi/generic/elidel.htm Link_out
Drugs.com http://www.drugs.com/cdi/pimecrolimus.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/eli1609.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Pimecrolimus Link_out
ATC Codes
  • D11AX15
AHFS Codes
  • 84:92.00
PDB Entries Not Available
FDA label show (230 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Bleomycin Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants like bleomycin. This combination is contraindicated
Carboplatin Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as carboplatin. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Carmustine Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as carmustine. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Chlorambucil Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as chlorambucil. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Cisplatin Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as cisplatin. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Cladribine Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as cladribine. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Clofarabine Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as clofarabine. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Food Interactions Not Available
Targets

1. Serine/threonine-protein kinase mTOR

Pharmacological action: yes
Actions: potentiator

Acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex

Organism class: human
UniProt ID: P42345 Link_out
Gene: FRAP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reitamo S, Remitz A, Kyllonen H, Saarikko J: Topical noncorticosteroid immunomodulation in the treatment of atopic dermatitis. Am J Clin Dermatol. 2002;3(6):381-8. Pubmed

2. FK506-binding protein 1A

Pharmacological action: unknown
Actions: potentiator

May play a role in modulation of ryanodine receptor isoform-1 (RYR-1), a component of the calcium release channel of skeletal muscle sarcoplasmic reticulum. There are four molecules of FKBP12 per skeletal muscle RYR. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides

Organism class: human
UniProt ID: P62942 Link_out
Gene: FKBP1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reitamo S, Remitz A, Kyllonen H, Saarikko J: Topical noncorticosteroid immunomodulation in the treatment of atopic dermatitis. Am J Clin Dermatol. 2002;3(6):381-8. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:41