KRH-2731

CXC chemokine receptor‐4, the receptor for stromal cell‐derived factor‐1α as well as human immunodeficiency virus type 1, belongs to the chemokine receptor family and has been shown to play a critical role in directing the migration of cancer cells to sites of metastasis as well as human immunodeficiency virus type 1 infection. We had previously reported that a duodenally absorbable CXC chemokine receptor‐4 antagonist, KRH‐1636, showed a potent anti‐human immunodeficiency virus type 1 activity both in vivo and in vitro. In this study, we initially examined the effect of the compound and its derivatives on stromal cell‐derived factor‐1α‐mediated chemotaxis of cancer cells in order to evaluate if they could be applicable as a novel inhibitor of cancer metastasis. We found that both KRH‐2731 and KRH‐3955 were highly potent antagonists of stromal cell‐derived factor‐1α‐mediated chemotaxis, i.e. the derivatives exhibited 50% effective concentrations of less than 10 nM, for more than 1000‐fold efficacy improvement over the prototype KRH‐1636. We further demonstrated the greater anti‐human immunodeficiency virus type 1 efficacy of the derivatives compared with the original KRH‐1636. Taken together, the KRH‐1636 derivatives KRH‐2731 and KRH‐3955 may be promising as a novel inhibitory drug for cancer metastasis as well as for human immunodeficiency virus type 1 infection. (Cancer Sci 2009; 100: 778ndash;781)