DAPH

DAPH is a phthalimide with diverse biological activities.^1,2,3,4 It is an EGFR inhibitor that selectively inhibits the EGFR intracellular kinase domain over v-Abl, c-Src, PKCα, PKCβ1, PKCβ2, and PKCγ (IC₅₀s = 0.3, >50, 16, 6, 30, 4.8, and 30 μM, respectively) and a panel of 11 other kinases.¹ It also inhibits EGFR autophosphorylation in A431 human epidermoid carcinoma cell membranes and intact cells (IC₅₀s = 1 and <10 μM, respectively). DAPH inhibits contractions induced by phenylephrine (Item No. 17205) in isolated rat endothelium-denuded aortic rings in a concentration-dependent manner.² It inhibits aggregation of amyloid-β (1-42) (Aβ42) peptide (Item No. 20574), disaggregates preformed Aβ42 fibrils, and inhibits calcium influx into mouse CATH.a neuronal cells when used at a concentration of 10 μM.³ DAPH also inhibits aggregation of a Sup35 yeast prion protein fragment that contains its N-terminal and highly charged middle domains (IC₅₀ = 0.58 μM).⁴

The information regarding the kinase IC₅₀ values and reduction in EGFR autophosphorylation was drawn from a paper that has been retracted; however, the information specified in the retraction statement has not been included.¹

WARNING This product is not for human or veterinary use.

1. Buchdunger, E., Trinks, U., Mett, H., et al. 4,5-Dianilinophthalimide: A protein-tyrosine kinase inhibitor with selectivity for the epidermal growth factor receptor signal transduction pathway and potent in vivo antitumor activity. Proc. Natl. Acad. Sci. USA 91(6), 2334-2338 (1994).

2. Ulu, N., Gurdal, H., Landheer, S.W., et al. α1-Adrenoceptor-mediated contraction of rat aorta is partly mediated via transactivation of the epidermal growth factor receptor. Br. J. Pharmacol. 161(6), 1301-1310 (2010).

3. Blanchard, B.J., Chen, A., Rozeboom, L.M., et al. Efficient reversal of Alzheimer’s disease fibril formation and elimination of neurotoxicity by a small molecule. Proc. Natl. Acad. Sci. USA 101(40), 14326-14332 (2004).

4. Wang, H., Duennwald, M.L., Roberts, B.E., et al. Direct and selective elimination of specific prions and amyloids by 4,5-dianilinophthalimide and analogs. Proc. Natl. Acad. Sci. USA 105(20), 7159-7164 (2008).