Table 1 Abl kinase inhibitors with... | American Society of Hematology

Table 1

Abl kinase inhibitors with anti-T315>I activity

Compound	Ba/F3 cellular proliferation IC₅₀ (nM)			Purified enzyme IC₅₀ (nM)		Stage of development	Reference
Compound	Native Bcr-Abl	Bcr-Abl^T315I	Parental	Native Abl	Abl^T315I	Stage of development	Reference
MK-0457	100-200	100-200	100-200	10-2200*	30-3700*	Phase 2 clinical trials	42,–44
ON012380	10	7.5	NR	NR	1.38	Preclinical	48
SGX70393	12	7.3	>3000†	14.8†	4.2†	Preclinical	45
TG101223	NR	500	>5000	NR	50	Preclinical	47
AP24534	2	14	NR	3	31	Preclinical	46

Compound	Ba/F3 cellular proliferation IC₅₀ (nM)			Purified enzyme IC₅₀ (nM)		Stage of development	Reference
Compound	Native Bcr-Abl	Bcr-Abl^T315I	Parental	Native Abl	Abl^T315I	Stage of development	Reference
MK-0457	100-200	100-200	100-200	10-2200*	30-3700*	Phase 2 clinical trials	42,–44
ON012380	10	7.5	NR	NR	1.38	Preclinical	48
SGX70393	12	7.3	>3000†	14.8†	4.2†	Preclinical	45
TG101223	NR	500	>5000	NR	50	Preclinical	47
AP24534	2	14	NR	3	31	Preclinical	46

The IC₅₀ value is the concentration of inhibitor resulting in a 50% reduction in cell viability.^8,12,21,29

NR indicates not reported.

Lower values were obtained using full-length Abl in the presence of 10 μM ATP⁴³; higher values were obtained with the isolated kinase domains in the presence of 2.2 mM ATP.⁴⁴

†

T.O., C.A.E., M.W.D., unpublished observations, 2006.

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