Dafadine-A Chemical Properties

storage temp. 

2-8°C

solubility 

DMSO: soluble15mg/mL, clear

form 

powder

color 

white to beige

InChI

1S/C23H25N3O3/c1-16-4-3-5-17(2)22(16)28-15-20-14-21(25-29-20)23(27)26-12-8-19(9-13-26)18-6-10-24-11-7-18/h3-7,10-11,14,19H,8-9,12-13,15H2,1-2H3

InChIKey

WNSNPYIHDMIFOO-UHFFFAOYSA-N

SMILES

N3(CCC(CC3)c4ccncc4)C(=O)c1n[o]c(c1)COc2c(cccc2C)C

Safety Information

WGK Germany 

3

Storage Class

11 - Combustible Solids

Dafadine-A Usage And Synthesis

Uses

Dafadine-A is a selective inhibitor of DAF-9 cytochrome P450 in the nematode Caenorhabditis elegans. Dafadine-A inhibits the mammalian ortholog of DAF-9 (CYP27A1). Dafadine-A does not inhibits DAF-12 and sterol- and oxysterol-metabolizing P450s[1].

Definition

ChEBI: Dafadine A is an N-acylpiperidine obtained by formal condensation of the carboxy group of 5-[(2,6-dimethylphenoxy)methyl]-1,2-oxazole-3-carboxylic acid with the secondary amino group of 4-(pyridin-4-yl)piperidine. It has a role as a P450 inhibitor and a geroprotector. It is a member of pyridines, a N-acylpiperidine, a member of isoxazoles, an aromatic ether and an aromatic amide.

Biological Activity

Dafadine A is a selective inhibitor of C. elegans DAF-9 cytochrome P450, a key regulator of dauer formation, developmental timing and longevity. C. elegans has four life stages. In harsh environmental conditions, nematodes can convert to the L3 stage, known as the ""non-aging"" dauer stage, in which development ceases until improved conditions are sensed. Dafadine A can induce dauer formation and increased longevity in wild-type worms raised in nonstressful conditions. Dafadine A is the only inhibitor known to robustly inhibit DAF-9 in wild-type worms. It does not inhibit DAF-12 activity. Dafadine is active in mammalian systems, inhibiting CYP27A1, the mammalian functional ortholog of DAF-9 th at oxidizes 4-cholesten-3-one to make 26-hydroxy-4-cholesten-3-one and Δ4-dafachronic acid, without inhibiting other sterol- and oxysterol-metabolizing P450s such as CYP7A1 or CYP7B1.

References

[1] Luciani GM, et al. Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans. Nat Chem Biol. 2011 Nov 6;7(12):891-3. DOI:10.1038/nchembio.698
[2] Wang X, et al. Cholesterol neutralized vemurafenib treatment by promoting melanoma stem-like cells via its metabolite 27-hydroxycholesterol. Cell Mol Life Sci. 2024 May 22;81(1):226. DOI:10.1007/s00018-024-05267-3