Table 4. sPLA₂ Potency and Optimization Parameters for Compounds 4–9.

entry	R	sPLA2-IIa IC50 (μM)a	sPLA2-V IC50 (μM)a	sPLA2-X IC50 (μM)a	plasma ICu,50 (nM)b	HEP Clint (μL/min/10–6 cells)c	OATP1B1 IC50 (μM)d
4	H	0.012	0.36	0.28	7	5.2	2
7	Me	0.011	0.07	0.75	1	9.6	NAe
8	Et	0.021	0.07	0.43	0.8	25	NDf
9	CyPr	0.018	0.25	0.58	0.9	21	NDf
(S)-7	(S)-Me	0.038	1.2	3.8	ND	9.3	NDf
(R)-7	(R)-Me	0.010	0.04	0.4	0.1	12	NAe

^aMean of at least two experiments. Experimental errors within 20% of value.

^bCalculated as Plasma sPLA₂ IC₅₀ (μM) × unbound fraction in human plasma (F_u)/100.

^cIntrinsic clearance of test compounds after incubation with human hepatocytes.

^dInhibition of pivastatin uptake to HEK293 cells transfected with human OATP1B1.

^eNot active at maximum tested concentration (25 μM).

^fNot determined.