There is the mechanism that mutated tyrosine kinase follows the treatment of cancer patient and the main representative acquired resistance of molecular targeted therapy. Here, it is mutated snakelike receptor, describes smoothened (SMO), causes resistance Dao Hedgehog mouse (Hh) approach restrainer, such as in medulloblastoma. Amino acid replacement SMO in conserved residues keeps Hh signalings, but has led to and be unable to Hh pathway inhibitors, GDC-0449, inhibits approach to bind SMO. In some embodiments, present disclose provides new mutant SMO albumen and nucleic acid and for sieve method, it is that species specificity adjusting mutant SMO shows drug resistance that drug is screened with SMO methods with detection mutation.