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Chemical Compound Review

CHEMBL257119     N'-[2-(5-diethylaminopentan- 2-ylamino)-6...

Synonyms: SureCN2639296, NSC-23766, AC1L8XPC, KB-145985, Nsc 23766, ...
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Disease relevance of NSC23766

  • Application of a Rac-specific inhibitor, the chemical compound NSC23766, to schwannoma cells restored neuronal interaction [1].
  • Treatment of a ZR-75-1 breast cancer cell line stably transfected with AND-34 plus 2 micromol/L LY294002 or 10 micromol/L NSC23766, a Rac-specific inhibitor, abrogated AND-34-induced resistance to ICI 182,780 [2].

High impact information on NSC23766

  • The chemical compound NSC23766 was identified by a structure-based virtual screening of compounds that fit into a surface groove of Rac1 known to be critical for GEF specification [3].
  • Thus, NSC23766 constitutes a Rac-specific small-molecule inhibitor that could be useful to study the role of Rac in various cellular functions and to reverse tumor cell phenotypes associated with Rac deregulation [3].
  • Schwannomin and Pak phosphorylation levels are not reduced in response to lowering Rac-GTP levels with NSC23766 [4].
  • In contrast, farnesyl transferase inhibitors blocked iNOS protein expression induced by LPS and IL-1beta, whereas NSC23766 had no effect [5].
  • Thus, NSC23766 is a lead small molecule inhibitor of Rac activity and could be useful for studying Rac-mediated cellular functions and for modulating pathological conditions in which Rac-deregulation may play a role [6].

Biological context of NSC23766


Anatomical context of NSC23766

  • Intraperitoneal administration of NSC23766 to laboratory mice resulted in effective Rac GTPase suppression and hematopoietic stem cell mobilization from the bone marrow to the peripheral blood, similar to the effects of genetically targeted disruption of Rac GTPases in the animals [7].


  1. Temporal control of Rac in Schwann cell-axon interaction is disrupted in NF2-mutant schwannoma cells. Nakai, Y., Zheng, Y., MacCollin, M., Ratner, N. J. Neurosci. (2006) [Pubmed]
  2. AND-34 activates phosphatidylinositol 3-kinase and induces anti-estrogen resistance in a SH2 and GDP exchange factor-like domain-dependent manner. Felekkis, K.N., Narsimhan, R.P., Near, R., Castro, A.F., Zheng, Y., Quilliam, L.A., Lerner, A. Mol. Cancer Res. (2005) [Pubmed]
  3. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Gao, Y., Dickerson, J.B., Guo, F., Zheng, J., Zheng, Y. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Phosphorylation of the NF2 tumor suppressor in Schwann cells is mediated by Cdc42-Pak and requires paxillin binding. Thaxton, C., Lopera, J., Bott, M., Baldwin, M.E., Kalidas, P., Fernandez-Valle, C. Mol. Cell. Neurosci. (2007) [Pubmed]
  5. The role of Rho-associated kinase in differential regulation by statins of interleukin-1beta- and lipopolysaccharide-mediated nuclear factor kappaB activation and inducible nitric-oxide synthase gene expression in vascular smooth muscle cells. Wei, C.Y., Huang, K.C., Chou, Y.H., Hsieh, P.F., Lin, K.H., Lin, W.W. Mol. Pharmacol. (2006) [Pubmed]
  6. Rational design and applications of a Rac GTPase-specific small molecule inhibitor. Akbar, H., Cancelas, J., Williams, D.A., Zheng, J., Zheng, Y. Meth. Enzymol. (2006) [Pubmed]
  7. Structure-function based design of small molecule inhibitors targeting Rho family GTPases. Nassar, N., Cancelas, J., Zheng, J., Williams, D.A., Zheng, Y. Current topics in medicinal chemistry. (2006) [Pubmed]
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