Journal of Chemical Crystallography

, Volume 37, Issue 10, pp 679–683 | Cite as

Tyrphostin Tumor Growth Inhibitors of EGFR and ErbB2 Tyrosine Kinase

  • Naijue Zhu
  • Peter Tran
  • Nicole Bell
  • Cheryl L. Klein Stevens
Original Paper


Tyrosine kinase inhibitors are small molecules that bind to the ATP binding site of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and disrupt the uncontrolled signaling reactions in cancer cells by inhibiting tyrosine phosphorylation. Tyrphostins (or malononitriles) are one class of compounds known to function as tyrosine kinase inhibitors. Our focus is to determine the structural features of these molecules that make them candidates for tyrosine kinase inhibitors. In this study, the X-ray crystal structures of four compounds shown to have EGFR tyrosine kinase inhibition have been determined. They are 4-methoxybenzylidenemalononitrile, (3,4,5-trihydroxybenzylidene) malononitrile, α-cyano-(3,5-di-t-butyl-4-hydroxy)thiocinnamide, and N-(3′,4′-dihydroxybenzylidenecyanoacetyl)indoline. Crystallographic data: 4-methoxybenzylidenemalononitrile, P21/c, a = 3.9173(6) Å, b = 24.909(3) Å, c = 9.6487(9) Å, β = 91.10(1)°, V = 941.3(2) Å3; (3,4,5-trihydroxybenzylidene) malononitrile, P21/c, a = 7.0065(5) Å, b = 10.7158(9) Å, c = 13.4191(10) Å, β = 102.986(6)°, V = 981.7(1) Å3; α-cyano-(3,5-di-t-butyl-4-hydroxy)thiocinnamide, P1bar, a = 9.6640(19) Å, b = 9.7204(13) Å, c = 10.3305(18) Å, α = 88.93(1)°, β = 83.88(2)°, γ = 66.12(1)°, V = 882.0(3) Å3; N-(3′,4′-dihydroxybenzylidenecyanoacetyl)indoline, P1bar, a = 7.8887(7) Å, b = 8.220(1) Å, c = 12.967(2) Å, α = 94.42(1)°, β = 99.45(9)°, γ = 118.37(8)°, V = 718.0(2) Å3.


Tyrosine kinase inhibitors Malononitrile Tyrphostin X-ray crystal structures 



Support of this research from the Department of Defense (PC 030945) and the ACS Slayton Evans Research Award to N. Bell is gratefully acknowledged. NIH-MARC Program (GM00716) for support of P. Tran is gratefully acknowledged.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Naijue Zhu
    • 1
  • Peter Tran
    • 1
  • Nicole Bell
    • 1
  • Cheryl L. Klein Stevens
    • 1
  1. 1.Department of ChemistryXavier University of LouisianaNew OrleansUSA

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