Pimecrolimus is a semi-synthetic, macrocyclic lactone derived from ascomycin by activation of the 32-hydroxy group with a triflate ester, and nucleophilic substitution with chloride under phase transfer conditions to provide the chloro analogue. Pimecrolimus has been targeted for treatment of inflammatory skin disorders. Pimecrolimus is known for its anti-inflammatory and immunomodulatory properties.
Pimecrolimus is soluble in ethanol, methanol, DMF or DMSO, but is practically insoluble in water.
|Mechanism of Action||As a tacrolimus analog, Pimecrolimus binds to receptor protein FKBP12. The complex then binds to mTOR preventing it from interacting with target proteins. The result is an inhibition of pro-inflammatory cytokines by T-cells and mast cells. It is more selective than tacrolimus and has no effect on dendritic (Langerhans) cells.|
|Spectrum||Pimecrolimus is active against fungi.|
|General Applications||Pimecrolimus can be used in pretreating melanocytes in a colorimetric MTT assay to measure the proliferation rate.|
|Eukaryotic cell culture applications||
Pimecrolimus is a specific inhbitor of the production of pro-inflammatory cytokines from T-cells and mast cells grown in vitro (Grassberger et al, 1999).
Pimecrolimus was used to study its ability to stimulate melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Doses of 1, 10, or 100 nM were neither mitogenic or cytotoxic. The compound enhances melanin synthesis and promotes melanocyte migration directly (Xu et al, 2017).
Grassberger M et al (1999) A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol.141(2):264-273. PMID 10468798
Gyollai V and Szabo C (2007) Method for preparing Pimecrolimus. US Patent 7,279,571
Nghiem P, Pearson G, Langley RG (2002) Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J. Am. Acad. Dermatol. 46(2):228-241 PMID 11807435
Schopf RE (2002) Pimecrolimus. Novartis. Curr. Opin. Investig. Drugs 3:720
Xu P, Chen J, Tan C, Lai RS, Min ZS (2017) Pimecrolimus increases the melanogenesis and migration of melanocytes in vitro. Korean J. Physiol. Pharmacol. 21(3):287-292. PMID: 28461770