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. Author manuscript; available in PMC: 2014 Oct 10.
Published in final edited form as: J Med Chem. 2013 Sep 30;56(19):10.1021/jm401067s. doi: 10.1021/jm401067s

Table 1.

Biochemical and cell-based activities, microsome stability and CYP inhibition properties of LP10 and analogs 1 and 2

compound KD
(nM)		 EC50
(µM)		 Microsome
stability
t1/2 (min)a 		% inhibition of human CYPs
at 10 µM (unless indicated
otherwise)
h m 1A2 2C9 2D6 3A4
graphic file with name nihms528832t1.jpg ≤42 0.65 - - - - - -
graphic file with name nihms528832t2.jpg ≤5 c 0.68 3.8 4.2 41 (23)d 99 (92)d 93 (77)d 96 (75)d
graphic file with name nihms528832t3.jpg 140 1.5 6.5 6.9 55 (21)d 99 (92)d 96 (62)d 99 (77)d
Sutentb - - 30 11 - - - -
Furafylline (40 µM)b - - - - 86 5 4 8
Sulfaphenazoleb - - - - 20 92 7 21
Quinidineb - - - - 23 9 90 36
Ketoconazole (1 µM)b - - - - 22 22 4 95
a

Stability of compounds in human (h) and mouse (m) liver microsomes, using sunitinib as a reference control.

b

Reference compounds for microsome stability and human CYP inhibition

c

KD of ≤5 nM (a hundredth of the target concentration) was estimated from the titration curves at 0.5 µM TcCYP51 for the tightest binding inhibitors, if a plateau was reached at the stoichiometric enzyme-inhibitor ratio.

d

Values in parentheses are % inhibition of the indicated human CYPs at 1 µM.