Table 1 Evolution of CA-170: profiles of hit and lead compounds.

#	Structure	Class of compound	Rescue of proliferation EC₅₀ nM	Plasma stability (% remaining at 4 h)			Mice PK parameters
#	Structure	Class of compound	Rescue of proliferation EC₅₀ nM	Mice	Rat	Human	Clearance (mL/hr/kg)	AUCi iv(0-α) (hr*ng/mL)	AUC po (0-α) (hr*ng/mL)	Cmax (ng/ml)	% F
NP-01		Linear peptide	81	<30	<30	<30	Not analyzed due to low plasma stability of the compound
PM-823		Head to tail cyclic peptide	55	>95	>95	>95	1376	2185	495	554.21	6.8
PM-116		Linear peptide	6	<30	<30	<30	Not analyzed due to low plasma stability of the compound
PM-13		Linear peptidomimetic	21 ± 2.8	37	30	37	10697	344	653	342	16.2
PM-105		PM-13 Retro-inverso	33 ± 2.8	62	64	67	1011	3000	2600	2908	15.5
PM-209		Cyclic version of PM-13	40.3 ± 10.4	>95	91	>95	743	4032	5502	3730	13.6
PM-219		PM-209 Retro-inverso	32.6 ± 10.5	>95	90	82	327	9535	11553	6437	13
CA-170		Amino acid fused heterocycles	15.4 ± 1.3	>95	>95	>95	723	4205	19574	1723	50

Functional activity was tested in a splenocyte-based assay by measuring the ability of the test peptides to rescue PD-L1 mediated inhibition of proliferation. For initial hit compounds such as NP-01, PM-823, and PM-116 data is presented as EC₅₀ value for rescue of proliferation from a set of triplicate values (n = 1). For all lead compounds PM-13, PM-105, PM-209, PM-219, and CA-170 data is represented as mean ± S.D of two independent studies. Mice, rat, and human plasma stability values were represented as mean of duplicate of percent parent compound remaining at 4 h, tested at 10 μM. Mice PK parameters including oral bioavailability were determined from intravenous and oral route of administration of compounds at 1 mg kg⁻¹ and 30 mg kg⁻¹, respectively.

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