Yongsheng Ma, Eric Carter, Xiaomei Wang, Chang Shu

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Indolinone Derivatives Inhibit Constitutively Activated KIT Mutants and Kill Neoplastic Mast Cells Yongsheng Ma, Eric Carter, Xiaomei Wang, Chang Shu Journal of Investigative Dermatology Volume 114, Issue 2, Pages 392-394 (February 2000) DOI: 10.1046/j.1523-1747.2000.00888.x Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Effects of indolinone derivatives on phosphorylation of wild-type and mutant KITs. Upper panel: Anti-phosphotyrosine (pTyr) blots of immunoprecipitated wild-type (WT) KIT expressed in COS cells and of mutant KITs expressed in C2 and P815 cells stimulated (+), or not (–), with stem cell factor (SCF, 100 ng per ml, 10 min) after incubation (+), or not (–), with indolinone derivatives (5 μM for COS and C2 cells, 40 μM for P815 cells, 30 min) show that SU4984, SU6663, SU6577, and SU5614 inhibit wild-type KIT phosphorylation but variably inhibit C2 and P815 KIT phosphorylation. SU4984, SU6577, and SU5614 are effective against KIT containing an activating juxtamembrane domain mutation in C2 cells, whereas only SU6577 can significantly suppress KIT bearing an activating kinase domain mutation in P815 cells. Lower panel: Re-probing the anti-pTyr blots (after stripping) with anti-KIT antibody shows that comparable amounts of receptor are present in different lanes. Journal of Investigative Dermatology 2000 114, 392-394DOI: (10.1046/j.1523-1747.2000.00888.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Effects of indolinone derivatives on neoplastic mast cell growth. Cell proliferation assay of C2 and P815 cells treated daily with 1 μM and 10 μM, respectively, of indolinone derivatives shows that SU4984, SU6577, and SU5614 kill C2 cells, and SU4984 and SU6577 kill P815 cells. Note that the growth curves of P815 cells treated with SU4984 and SU6577 overlap. Results (mean ± SEM) represent averages of triplicate cultures. Journal of Investigative Dermatology 2000 114, 392-394DOI: (10.1046/j.1523-1747.2000.00888.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions