5.33916

KIFC1 Inhibitor, AZ82

• Sinonimo/i: KIFC1 Inhibitor, AZ82, 5-Methyl-N-(( R)-1-oxo-1-(( R)-pyrrolidin-3-ylamino)-3-(6-(3-(trifluoromethoxy)phenyl)pyridin-3-yl)propan-2-yl)-4-propylthiophene-2-carboxamide, Tctex7 Inhibitor, Knsl2 Inhibitor, MT/KIFC1 Inhibitor, Bm4137 Inhibitor, HSET Inhibitor, Kinesi, 5-Methyl-N-((R)-1-oxo-1-((R)-pyrrolidin-3-ylamino)-3-(6-(3-(trifluoromethoxy)phenyl)pyridin-3-yl)propan-2-yl)-4-propylthiophene-2-carboxamide, Tctex7 Inhibitor, Knsl2 Inhibitor, MT/KIFC1 Inhibitor, Bm4137 Inhibitor, HSET Inhibitor, Kinesin F
• Formula empirica (notazione di Hill): C₂₈H₃₁F₃N₄O₃S
• Numero CAS: 1449578-65-7
• Peso molecolare: 560.63
• Codice UNSPSC: 12352200
• NACRES: NA.77

Proprietà

• Saggio: ≥96% (HPLC)
• Livello qualitativo: 100
• Forma fisica: film
• Produttore/marchio commerciale: Calbiochem^®
• Condizioni di stoccaggio: OK to freeze; protect from light
• Colore: yellow
• Solubilità: DMSO: 50 mg/mL
• Temperatura di conservazione: 2-8°C

Descrizione

Descrizione generale

A cell-permeable pyridinylpropanylthiophene-carboxamide compound that acts as a potent, reversible, and ATP-competitive (K_i = 43 nM) and microtubule (MT) non-competitive inhibitor of MT-stimulated ATPase activity of KIFC1 (IC₅₀ = 300 nM). However, it does not affect the basal ATPase activity even at high concentrations (~100 µM). Binds to the MT/KIFC1 complex (K_d of 690 nM) with high-affinity and blocks ATP binding and release of ADP. Does not directly interact with KIFC protein that is not associated with MT. Exhibits high degree of selectivity against a panel of nine kinesin motor proteins at a concentration (~ 5 µM) where KIFC1 activity is reduced by 95%. Causes mitotic delay, multipolar spindle formation and centrosome declustering in centrosome-amplified BT-549 cancer cells without affecting normal cells. Also shown to prevent Eg5 inhibition induced monopolar spindles and restores bipolar mitotic spindle formation in HeLa cells at 400 nM.

A cell-permeable pyridinylpropanylthiophene-carboxamide compound that exhibits selective affinity toward MT/microtubule-bound KIFC1 motor domain (Q305-K673; K_d = 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 (K_i = 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.

Azioni biochim/fisiol

Cell permeable: yes

Primary Target
MT/KIFC1

Reversible: yes

Confezionamento

Packaged under inert gas

Attenzione

Toxicity: Standard Handling (A)

Ricostituzione

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Altre note

Reference: Wu, J., et al. 2013. ACS Chem. Biol.8, 2201.

Note legali

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

Informazioni sulla sicurezza

• Codice della classe di stoccaggio: 13 - Non Combustible Solids
• Classe di pericolosità dell'acqua (WGK): WGK 3
• Punto d’infiammabilità (°F): Not applicable
• Punto d’infiammabilità (°C): Not applicable