In 2004, Gu XJ et al. identified novel HSP90 inhibitors and obtained two hits with HSP90 inhibitory activity.420 Structure modification based on the hits as starting points led to the discovery of XL888 (Table 2) that has improved potency and pharmacokinetic properties, and thus entered into clinical trials.421 In addition to evaluated in solid tumors as a single agent, XL888 also was used to treat unresectable melanoma in combination with vemurafenib and cobimetinib in phase I trials. This evidence concerns the gene HSP90AB1 and melanoma.