FK506 monohydrate

Cas：109581-93-3

Product Information：

Tacrolimus is 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.

Chemical Formula: C44H71NO13

Exact Mass: 821.4925

Molecular Weight: 822.05

Elemental Analysis: C, 64.29; H, 8.71; N, 1.70; O, 25.30

Synonym:

FR 900506

FR900506

LCP-Tacro

Prograf

FK 506

FK-506

FK506

Protopic

Tacrolimus

Tacrolimus hydrate

Tsukubaenolide hydrate

Chemical Name: 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*))-

InChi Key:

NWJQLQGQZSIBAF-MLAUYUEBSA-N

InChi Code: 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

Smiles Code:

CO[C@@H]1C[C@H](/C=C([C@H]2OC([C@@H]3CCCCN3C(C([C@@]4(O[C@@H]([C@@H](OC)C[C@H]4C)[C@@H](OC)C[C@H](C/C(C)=C/[C@H](C(C[C@@H]([C@H]2C)O)=O)CC=C)C)O)=O)=O)=O)\C)CC[C@H]1O.O

Technical Data：

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.03.00

In Vitro：

Tacrolimus monohydrate (FK506 monohydrate; Fujimycin monohydrate; FR900506 monohydrate) inhibits calcium-dependent events, such as IL-2 gene transcription, NO synthase activation, cell degranulation, and apoptosis. Tacrolimus also potentiates the actions of glucocorticoids and progesterone by binding to FKBPs contained within the hormone receptor complex, preventing degradation. The agent may enhance expression of the TGFβ-1 gene in a fashion analogous to that demonstrated for CsA. T cell proliferation in response to ligation of the T cell receptor is inhibited by Tacrolimus. Treatment with a low concentration of Tacrolimus (FK506,10 μg/L) does not significantly affect the proliferation of MH3924A cells (P=0.135). Upon treatment with higher concentrations of Tacrolimus (100-1,000 μg/L), the proliferation of MH3924A cells is significantly enhanced (P<0.01). Treatment with AMD3100 at any concentration (10, 50 or 100 μg/L), has no obvious effect on MH3924A cell proliferation (P>0.05). However, when different concentrations of AMD3100 are combined with 100 μg/L Tacrolimus, the in vitro proliferation of MH3924A cells is increased (P<0.01).

In Vivo：

The therapeutic effect of Tacrolimus is investigated on progression and perpetuation of colitis by administering Tacrolimus to Dextran sulfate sodium (DSS)-treated mice from Days 10 to 16 or to 23. At Days 17 and 24, colon length is significantly shortened, and colon weight is significantly higher in DSS-treated control animals than in normal animals. In addition, colon weight per unit length in the control group is more than twice that in the normal group. While both 7 and 14 d treatment with Tacrolimus significantly suppresses increases in colon weight per unit length in DSS-treated animals compared with the control group, this treatment does not actually restore the colon shortening. In addition, this inhibitory effect of Tacrolimus on increases in colon weight per unit length is more pronounced with 14-d than 7-d treatment, as shown by the inhibitory percentages (59% vs. 28%).

References：

1. Dodi PL. Immune-mediated keratoconjunctivitis sicca in dogs: current perspectives on management. Vet Med (Auckl). 2015 Oct 30;6:341-347. doi: 10.2147/VMRR.S66705. eCollection 2015. Review. PubMed PMID: 30101119; PubMed Central PMCID: PMC6067592.

2. Kumar A, Singh N. Calcineurin Inhibition and Protein Kinase A Activation Limits Cognitive Dysfunction and Histopathological Damage in a Model of Dementia of the Alzheimer's Type. Curr Neurovasc Res. 2018 Aug 13. doi: 10.2174/1567202615666180813125125. [Epub ahead of print] PubMed PMID: 30101704.

3. Shin MH, Song GW, Lee SG, Hwang S, Kim KH, Ahn CS, Moon DB, Ha TY, Jung DH, Park GC, Yun YI, Kim WJ, Kang WH, Kim SH, Jiang H, Lee S, Tak EY. Once-daily, prolonged-release tacrolimus versus twice-daily, immediate-release tacrolimus in de novo living-donor liver transplantation: a Phase 4, randomized, open-label, comparative, single-center study. Clin Transplant. 2018 Aug 11:e13376. doi: 10.1111/ctr.13376. [Epub ahead of print] PubMed PMID: 30098071.

4. Liu YJ, Fan H, Zhen WW, Yu X, Chen JT, Wang CD. Pooled analysis of the comparative efficacy between tacrolimus and infliximab for ulcerative colitis. Medicine (Baltimore). 2018 Aug;97(32):e11440. doi: 10.1097/MD.0000000000011440. PubMed PMID: 30095612.

5. Garaix F, Stern M, Lamy FX, Dubel L, Kamar N. Tacrolimus Granules for Oral Suspension as Post-Transplant Immunosuppression in Routine Medical Practice in France: The OPTIMOD Study. Ann Transplant. 2018 Aug 10;23:561-571. doi: 10.12659/AOT.908522. PubMed PMID: 30093607.

Products are for research use only. Not for human use.