. Author manuscript; available in PMC: 2021 May 14.

Published in final edited form as: J Med Chem. 2020 Apr 29;63(9):4790–4810. doi: 10.1021/acs.jmedchem.0c00015

Table 8.

Metabolic Stability Assay in Human Liver Microsomes

Sample	HLM (Final concentration of 0.5 mg protein/mL)
Sample	R2^a	T_1/2^b (min)	CL_int(mic)^c (μL/min/mg)	CL_int(liver)^d (mL/min/kg)	Remaining (T=60min)	Remaining (NCF^e=60min)
11l	0.9863	4.1	342.0	307.8	0.0%	93.4%
PF-74	0.9761	1.3	1080.3	972.3	0.3%	93.1%
Testosteron^e	0.9973	14.6	95.2	85.7	6.1%	84.0%
Diclofenac	0.9972	14.8	93.6	84.3	5.9%	94.8%
Propafenon^e	0.9722	6.9	201.4	181.2	0.3%	100.0%

R² is the correlation coefficient of the linear regression for determination of the kinetic constant (see raw data worksheet in the Supporting Information).

T_1/2 is half-life, and CLint(mic) is the intrinsic clearance.

CL_int(mic) = (0.693/half-life)/mg microsome protein per mL.

CL_int(liver) = CL_int(mic) × mg microsomal protein/g liver weight × g liver weight/kg body weight.

NCF: no cofactor. No NADPH regenerating system was added to the NCF sample (replaced by buffer) during the 60 min incubation. If the remaining amount is less than 60%, then non-NADPH dependent reaction occurs.