Skip to main content

Table 1 Structural alerts for human liver toxicity and their frequency of occurrence in each of the drug classes

From: Data-driven identification of structural alerts for mitigating the risk of drug-induced human liver injuries

Alert SMARTS a Hepatotoxic b (178) Possible hepatotoxic c (243) Nonhepatotoxic d (186) p-value e
1 C12CCCCC1C3C(CCC3)CC2 19 2 3 <0.0001
2 NN 14 13 0 <0.0001
3 a[C!R]C(=O)[OH] 11 7 0 0.0011
4 [#6]S(=O)(=O)N[#6] 18 16 3 0.0058
5 c1ccccc1[NH2] 7 4 0 0.013
6 O = [S;X3] 5 0 1 0.014
7 [S;X2&!R] 8 14 1 0.016
8 a[C!R](=O)a 10 4 1 0.029
9 C[F,Cl,Br,I] 21 23 7 0.039
10 C1CC1N 4 4 0 0.11
11 [O]c1ccc([N])cc1 5 4 1 0.25
12 N1c2ccccc2Sc2ccccc12 5 2 1 0.25
  1. aSMiles ARbitrary Target Specification (SMARTS), a language for describing molecular patterns from Daylight Information Systems, Inc. (ref. [18]). bDrugs known to cause clinically apparent acute human liver injuries; the total number is given in parentheses. cDrugs that may have been linked to some reports of human liver injuries, but have not been convincingly established as causing these injuries in their therapeutic doses, or have not been widely used for an extended period of time and, therefore, lack sufficient clinical data for a reliable classification. The total number of these drugs is given in parentheses. dDrugs that have been on the market for an extended period of time and are in widespread use, but have not been convincingly associated with clinically apparent acute human liver injuries. The total number of these drugs is given in parentheses. eProbability for a structural alert to have a specific occurrence pattern across the three drug classes by chance.