. Author manuscript; available in PMC: 2022 Jan 24.

Published in final edited form as: Leukemia. 2019 Jan 30;33(7):1663–1674. doi: 10.1038/s41375-018-0364-x

Table 1:

Structure-activity relationship of the PatA analogs and their plasma protein binding properties.



Compounds		Structure				IC₅₀, μM^a		Human serum protein binding (%) ^b		FBS protein binding (%)^b

		R₁	R₂	R₃	R₄	10% FBS	10% Plasma	Fraction Bound	Recovery	Fraction Bound	Recovery

	PatA (1)	NH₂	Me	H	H	0.13 ± 0.08	0.12 ± 0.09	97.4 ± 0.6	80.4 ± 12.8	98.7 ± 0.6	86.3 ± 4.3
	DMDA PatA (2)	H	H	H	H	0.64 ± 0.29	4.54 ± 1.92	99.6 ± 0.1	38.1 ± 7.5	99.1 ± 0.1	78.3 ± 2.7

β-amino variants	3	NH₂	H	H	H	0.30 ± 0.27	0.33 ± 0.25	86.7 ± 4.7	54.0 ± 2.6
	4	NHTCBoc	H	H	H	2.97 ± 2.64	6.71 ± 3.63
	5	NHAc	H	H	H	5.60 ± 6.64	7.01 ± 1.78

α-amino variants	S configuration
	6	H	H	NHBoc	H	0.83 ± 0.18	2.23 ± 1.10	99.6 ± 0.1	92.7 ± 3.9
	7	H	H	NHCOCF₃	H	0.55 ± 0.19	1.95 ± 1.60	99.3 ± 0.0	85.3 ± 2.3
	8	H	H	NHAc	H	0.26 ± 0.24	0.56 ± 0.39	78.0 ± 7.2	33.7 ± 1.2
	9	H	H	NHSO₂Me	H	0.35 ± 0.33	1.00 ± 0.90	94.0 ± 2.6	45.7 ± 1.5
	10	H	H	NH₂	H	2.47 ± 1.05	3.68 ± 1.95
	11	H	H	NHTCBoc	H	3.59 ± 0.46	6.81 ± 0.87

	R configuration
	12	H	H	H	NHTCBoc	1.88 ± 0.41	5.42 ± 0.24
	13	H	H	H	NHAc	0.04 ± 0.03	0.44 ± 0.17	93.9 ± 1.0	21.8 ± 0.1	95.6 ± 0.2	80.8 ± 1.9

^a.

Data represent the mean IC₅₀ values ± SD measured in least 3 individual CLL samples.

^b.

Data represent mean ± SD in triplicate measurements.