Kolaflavanone

Kolaflavanone is an biflavonoid allosteric inhibitor of Eg5. Kolaflavanone inhibits the ATPase and tyrosinase activities of Eg5 under both basal and microtubule-activated conditions, suppresses microtubule sliding activity, binds to the L5/α2/α3 allosteric pocket of Eg5, induces conformational changes of Eg5 and microtubule dissociation, interacts with aldehyde dehydrogenase, inhibits the ATPase activity of kinesin-1, and binds to HSA via pH-dependent forces. Kolaflavanone exhibits antihepatotoxic activity and can be used in studies related to Phalloidin (HY-P0028)-induced liver injury^[1][2][3]. In Vitro:Kolaflavanone (KLF) (0-250 μM; 20 min) inhibits the basal ATPase activity of the recombinant mouse Eg5 motor domain, with an IC₅₀ of 98 μM^[1].
Kolaflavanone (0-250 μM) inhibits the microtubule-activated ATPase activity of the recombinant mouse Eg5 motor domain, with an IC₅₀ of 125 μM^[1].
Kolaflavanone (100-150 μM; 900 s) inhibits the microtubule sliding rate of the recombinant mouse Eg5 motor domain, reducing the rate by approximately 53% at 100 μM and by approximately 59% at 150 μM, and induces the dissociation of microtubules from Eg5^[1].
Kolaflavanone (100 μM) acts as an allosteric inhibitor of the recombinant mouse Eg5 motor domain, and inhibits ATPase activity without directly competing for ATP or microtubule-binding sites^[1].
Kolaflavanone (100-150 μM) preferentially inhibits the microtubule-activated ATPase activity of the recombinant mouse Eg5 motor domain over the conventional kinesin-1 motor domain, and suppresses Eg5 activity by 62% at 150 μM^[1].
Kolaflavanone stably binds to the L5/α2/α3 allosteric pocket of the recombinant mouse Eg5 motor domain, forms hydrogen bonds with Glu118, Tyr211 and Arg221 residues, and induces conformational changes to reduce the flexibility of Eg5 and the solvation degree of the allosteric pocket^[1].
Kolaflavanone (0-62.50 µM; 15-40 °C) binds to human serum albumin (HSA) via a static quenching mechanism, with one binding site and moderate affinity (binding constant: 3.13-8.44 × 10³ L·mol^-1). This affinity decreases with increasing temperature, leading to a reduction in the binding rate of HSA at high temperatures^[3].
Kolaflavanone (0-56.25 µM; 25 °C) quenches the fluorescence of tyrosine and tryptophan residues in human serum albumin (HSA), and does not alter the hydrophobic microenvironment of these residues at 25 °C^[3].
Kolaflavanone undergoes non-radiative fluorescence resonance energy transfer with human serum albumin (HSA) at 25 °C, and the binding distance is 3.64 nm under the conditions of 25 °C and pH 7.4^[3]. In Vivo:Kolaflavanone (KLF) (10-50 mg/kg; i.p.; single administration) exhibits dose-dependent hepatoprotective activity against phalloidin (HY-P0028)-induced lethal liver injury in female Swiss mice, with a 100% survival rate at the dose of 50 mg/kg via intraperitoneal injection^[2].