Cryptocrome Activator, KL001

C₂₁H₂₂N₂O₄S

398.48

MFCD02086647

A cell-permeable carbazole compound that competes against FAD (flavin adenine dinucleotide) for cryptocrome (CRY) 1 & 2 binding, displaying little affinity toward other clock proteins (PER1/2, CLOCK, or BMAL1) or inhibitory activity against casein kinase (CKIα, CKIδ, and CK2) activity even at concentrations as high as 100 µM. Shown to selectively stabilize cellular CRY1/2 protein, but not mRNA, by preventing FBXL3-mediated CRY1/2 ubiquitination and proteasomal degradation, effectively lengthening the period and reducing the amplitude of the circadian transcription rhythms of Bmal1 and Per2 promoter-mediated transcription activity (IC₅₀ of intensity reduction = 14 and 0.82 µM, respectively, in U2OS reporter assay). KL001 is also reported to block glucagon-induced Pck1 and G6pc mRNA upregulation as well as glucose production in primary murine hepatocyte cultures (IC₅₀<8 µM). Longdaysin (Cat. No. 438075), in comparison, exerts its circadian perturbation activity via casein kinase inhibition.

Cell permeable: yes
Primary Target
Cryptocrome protein
Reversible: yes

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Hirota, T., et al. 2012. Science337, 1094.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

100

≥98% (HPLC)

solid

Calbiochem^®

OK to freeze
protect from light

off-white

DMSO: 50 mg/mL

ambient

2-8℃

OC(CN(CC1=CC=CO1)S(=O)(C)=O)CN2C3=C(C=CC=C3)C4=C2C=CC=C4

25 mg in Glass bottle
Packaged under inert gas

GHS07

Warning

H302

P264 - P270 - P301 + P312 - P501

Acute Tox. 4 Oral

11 - Combustible Solids

WGK 3