D. E. Gingrich, R. L. Hudkins / Bioorg. Med. Chem. Lett. 12 (2002) 2829–2831
2831
Table 2. Kinase activity (IC50, nM)a
Kaneko, M.;Saito, Y.;Saito, H.;Matsumoto, T.;Matsuda,
Y.;Vaught, J. L.;Dionne, C. A.;Angeles, T. S.;Glicksman,
M. A.;Neff, N. T.;Rotella, D. P.;Kauer, J. C.;Mallamo, J. P.;
Hudkins, R. L.;Murakata, C. J. Med. Chem. 1997, 40, 1863.
7. Wood, J. L.;Stoltz, B. M.;Dietrich, H.-J.;Pflum, D. A.;
Petsch, D. T. J. Am. Chem. Soc. 1997, 119, 9641.
Entry
PKC
TrkA
VEGFR2
MLK1
K252a 1
epi-K-252a 2
250ꢂ25
13ꢂ4
43ꢂ16
19ꢂ2
22ꢂ5
25ꢂ4
114b
1.2ꢂ0.2
aExperiment run in triplicate.
bSingle experiment.
8. (a) Camoratto, A. M.;Jani, J. P.;Angeles, T. S.;Maroney,
A. C.;Sanders, C. Y.;Murakata, C.;Neff, N. T.;Vaught, J. L.;
Isaacs, J. T.;Dionne, C. A. Int. J. Cancer 1997, 72, 673. (b)
Saporito, M.;Hudkins, R.;Maroney, A. Progress in Medicinal
Chemistry, Elsevier Science: Oxford 2002, Vol. 40, p 23. (c)
Murakata, C.;Kaneko, M.;Gessner, G.;Angeles, T. S.;Ator,
M. A.;O’Kane, T. M.;McKenna, B. A. W.;Thomas, B. A.;
Mathiasen, J. R.;Saporito, M. S.;Bozyczko-Coyne, D.;Hud-
kins, R. L. Bioorg. Med. Chem. Lett. 2002, 12, 147.
9. Murakata, C.;Sato, A.;Takahashi, M.;Kobayashi, E.;
Morimoto, M.;Akinaga, S.;Hirata, T.;Mochida, K.;Kase,
H.;Yamada, K.;Iwashashi, K. U.S. Patent 4,923,986, 1990;
Chem. Abstr. 1988, 110, 75861e.
Acknowledgements
The authors would like to acknowledge the contribu-
tions of Dr. Thelma Angeles, Dr. Shi Yang, and George
Gessner as well as the scientific discussions with Dr.
John Mallamo.
10. Zorbax RX C-8 column with an elution program of 10–
100% acetonitrile/water with 0.1% TFA over 40 min at 1.6
mL/min.
References and Notes
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2. Kase, H.;Iwahasi, K.;Matsuda, Y.;Yamada, K.;Taka-
11. (a) Gingrich, D. E.;Hudkins, R. H. WO 02/17914, 2002.
Chem. Abstr. 2002, 136, 216643m and references cited within.
(b) PKC activity was assessed using the Millipore Multiscreen
TCA ‘‘in plate’’ assay described in: Pitt, A. M.;Lee, C .
J. Biomol. Screening 1996, 1, 47.
hashi, M.;Murakata, C.;Sato, A.;Kanedo, M.
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Biochem.
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1995, 48, 535.
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5. Ohmori, K.;Ishii, H.;Manabe, H.;Satoh, H.;Tamura, T.;
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12. (a) Ruggeri, B. A.;Miknyoczki, S. J.;Singh, J.;Hudkins,
R. L. Curr. Med. Chem. 1999, 6, 845. (b) Angeles, T. S.;Stef-
fler, C.;Bartlett, B. A.;Hudkins, R. L.;Stephens, R. M.;
Kaplan, D. R.;Dionne, C. A. Anal. Biochem. 1996, 236, 49.
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