Table 1. Imatinib mesylate and PKC412 IC... | American Society of Hematology

Table 1.

Imatinib mesylate and PKC412 IC₅₀s of transforming c-KIT mutations

Cell line/c-KIT mutation	Reference	Location^*	Transforming	Imatinib mesylate IC₅₀, nM†	PKC412 IC₅₀, nM†‡
Ba/F3	—	—	—	7 274	304
kit WT and rhSCF, without IL-3	—	NA	—	237	138
kit WT and rhSCF, with IL-3	—	NA	—	24 360	345
delTYD(417-419) and 1	Gari et al, 1999⁸	EC	Yes	226	217
delTYD(417-419) and RG	Gari et al, 1999⁸	EC	Yes	45	95
A502Y503dup	Lux et al, 2000¹⁰	EC	Yes	196	206
V5301	Gari et al, 1999⁸	TM	No	ND§	ND§
V559D	Hirota et al, 1998¹¹	JM	Yes	11	265
V560G	Furitsu et al, 1993²	JM	Yes	53	82
delV559V560	Hirota et al, 1998¹¹	JM	Yes	15	146
R634W	Current study	K	Yes	198	85
K642E	Lux et al, 2000¹⁰	K	No	ND§	ND§
D816Y	Tsujimura et al. 1995³	K	Yes	840	33
D816V	Furitsu et al, 1993²	K	Yes	10 651	44
D820G	Pignon et al, 1997⁴	K	No	ND§	ND§
N822K	Beghini et al, 2002⁷	K	Yes	139	59
E839K	Longley et al, 1999¹²	K	No	ND§	ND§

Cell line/c-KIT mutation	Reference	Location^*	Transforming	Imatinib mesylate IC₅₀, nM†	PKC412 IC₅₀, nM†‡
Ba/F3	—	—	—	7 274	304
kit WT and rhSCF, without IL-3	—	NA	—	237	138
kit WT and rhSCF, with IL-3	—	NA	—	24 360	345
delTYD(417-419) and 1	Gari et al, 1999⁸	EC	Yes	226	217
delTYD(417-419) and RG	Gari et al, 1999⁸	EC	Yes	45	95
A502Y503dup	Lux et al, 2000¹⁰	EC	Yes	196	206
V5301	Gari et al, 1999⁸	TM	No	ND§	ND§
V559D	Hirota et al, 1998¹¹	JM	Yes	11	265
V560G	Furitsu et al, 1993²	JM	Yes	53	82
delV559V560	Hirota et al, 1998¹¹	JM	Yes	15	146
R634W	Current study	K	Yes	198	85
K642E	Lux et al, 2000¹⁰	K	No	ND§	ND§
D816Y	Tsujimura et al. 1995³	K	Yes	840	33
D816V	Furitsu et al, 1993²	K	Yes	10 651	44
D820G	Pignon et al, 1997⁴	K	No	ND§	ND§
N822K	Beghini et al, 2002⁷	K	Yes	139	59
E839K	Longley et al, 1999¹²	K	No	ND§	ND§

IC₅₀ indicates inhibitory concentration 50%; WT, wild type; rhSCF, recombinant human stem cell factor; IL-3, interleukin 3; NA, not applicable; EC, extracellular domain; TM, transmembrane domain; ND, not determined; JM; juxtamembrane, K, kinase domain.

Domain of c-KIT containing mutation.

†

Data are representative of 2 or more experiments performed in triplicate.

‡

L-3 rescued PKC412 growth inhibition (data not shown).

The indicated mutants did not transform Ba/F3 cells to factor independence. Thus, we were unable to test the ability of kinase inhibitors to inhibit growth in the absence of IL-3.

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