A cell-permeable pyridinylpropanylthiophene-carboxamide compound that exhibits selective affinity toward MT/microtubule-bound KIFC1 motor domain (Q305-K673; Kd = 690 nM), but not to uncomplexed KIFC1 or MT, and selectively inhibits MT-induced, but not basal, KIFC1 motor domain ATPase activity (IC50 = 300 nM; [KIFC1] = 30 nM, [MT] = 100 nM, [ATP] = 15 µM) in an ATP-competitive (Ki = 43 nM; [KIFC1] = 125 nM, [MT] = 1.5 µM) and MT-noncompetitive manner, effectively preventing ADP release, while displaying little potency against 9 other kinesin motor proteins (<15% or no inhibition at 5 µM against human CENP-E, Chromokinesin/KIF4A, Eg5, KIFC3, KIF3C, KInesin Heavy Chain/KIF5B, MCAK/KIF2C, MKLP1/KIF23, and A. nidulans BimC/KIF8). KIFC1 knockdown by siRNA or functional inhibition by AZ82 (0.4 to 1.2 µM) is shown to result in mitotic delay and multipolar spindle formation among BT549 population with extra centrosomes due to failure of chromosomes clustering. In cells with normal/two centrosomes, Eg5 inhibition causes monopolar spindles formation, while AZ82 co-treatment (400 nM) offsets the effect of Eg5 inhibition (5 nM AZD4877) and restores bipolar spindles phenotype in mitotic HeLa cells. Off-target cytotoxicity is reported when used at concentrations above 4 µM.
Biochem/physiol Actions
Cell permeable: yes
Primary Target MT/KIFC1
Reversible: yes
Packaging
Packaged under inert gas
Warning
Toxicity: Standard Handling (A)
Reconstitution
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Reference: Wu, J., et al. 2013. ACS Chem. Biol.8, 2201.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Storage Class Code
13 - Non Combustible Solids
WGK
WGK 3
Flash Point(F)
Not applicable
Flash Point(C)
Not applicable
Certificates of Analysis (COA)
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