Inhibition of Contact Sensitivity by Farnesylthiosalicylic Acid-Amide, a Potential Rap1 Inhibitor

We hypothesized that Ras proximate 1 (Rap1) functions as an additional target for farnesylthiosalicylic acid (FTS) or its derivatives, and that the inhibition of Rap1 in lymphocytes by these agents may represent a method for treating inflammatory disorders. Indeed, we found that FTS-amide (FTS-A) was able to inhibit the elicitation phase of delayed cutaneous hypersensitivity in vivo. This effect was associated with the inhibition of Rap1 more than with the inhibition of Harvey rat sarcoma viral oncogene (Ras). Moreover, FTS-A inhibited Rap1 and contact sensitivity far better than FTS. We suggest that FTS-A may serve as a possible therapeutic tool in contact sensitivity in particular and T-cell-mediated inflammation in general.