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. 2022 Jul 15;65(14):9662–9677. doi: 10.1021/acs.jmedchem.2c00704

Table 4. In Vitro/In Vivo Profile of Compound 27a.

27: MW = 557, TPSA = 112, log D7.4 = 3.8
human LM Clint/Hep Clint 7.2/41
rat LM Clint/Hep Clint 43/33
dog LM Clint/Hep Clint 20/21
cyno LM Clint/Hep Clint 55/80
cyno IV PK Cl (mL min–1 kg–1)b (Clu)c 31.8 (611)
cyno IV PK t1/2 (h) 2.9
a

LM Clint represents intrinsic clearance obtained from isolated microsomes (units = μL/min/mg) with NADPH, and Hep Clint represents intrinsic clearance obtained from isolated hepatocyte cells (units = μL/min/million cells).

b

Cynomolgus monkey, 0.5 mg/kg IV and 5 mg/kg PO dose. For IV and PO dosing, 27 was formulated in 5% DMSO + 5% kolliphor HS 15 + 90% saline vehicle. Cl: plasma clearance after administration of single IV bolus dose.

c

Clu: unbound in vivo clearance (in vivo cyno clearance/free fraction in cyno), free fraction calculated from plasma protein binding determined by ultracentrifugation method.