The Combination Index is calculated by the isobologram equation: where 1 and 2 are the doses of drug 1 and drug 2 in combination chemical catalogs that cause x% kinase inhibition and 1 and 2 are the doses of drug 1 and drug 2 alone, respectively, that cause x% kinase inhibition. CIb1 or CIN1 indicates greater than additive effects. For synergism the smaller the CI value is the greater the level of synergy and in the situation of antagonism the greater the value the greater the antagonism. Additivity, antagonism or synergismwere reviewed by isobologramwhere the X and Y intercepts indicate the concentrations of either compound alone resulting in a 50% kinase inhibition. The data point that falls between the axes shows the focus of the drug combination that inhibits the kinase activity. Data level above or below the straight line joining the intercepts indicate antagonistic or synergistic the consequence, respectively, while information points that fall on or close to the line joining the intercepts are indicate additive effects. It should be noted that significant synergism or antagonism Infectious causes of cancer is obtained when CIb0. 5 and CIb2. 0, respectively. Current architectural evidence shows the presence of a pocket in the C terminal lobe of the kinase domain of Abl. This pocket has recently been targeted by substances which include the 4,6 di substituted pyrimidines also called GNF 2 and GNF 5. Answer phase NMR and X ray crystallography, unambiguously show that GNF 2 binds for this recently recognized myr pocket. These results also confirm earlier in the day findings indicating that the Nmyristoylated peptide of Abl is able to displace Bcr?Abl or Abl from the GNF 2 affinity matrix. Therefore, these substances are referred to as myr pocket binders to differentiate them from the ATP pocket binders like nilotinib, imatinib or dasatinib. GNF 2, GNF 5, myristate and the N terminal myr Abl peptide are able to bind to the myr pocket of Abl229?515, however, not to the shorter edition of the Abl kinase domain as demonstrated Ibrutinib molecular weight by solution NMR. The kinase domain of Abl lacking the 15 proteins at the C terminus is not able to join myr pocket binders as it cannot form the helix I that is an essential structural element for the binding of the myristate moiety. b shows the general crystal structure of Abl kinase domain with GNF 2 liganded to the myr pocket and imatinib bound to the ATP binding site. It ought to be emphasized, that only those Abl kinase domain structures that contain imatinib bound to the ATP binding pocket have now been able to be solved with the myr pocket binders. The requirement for ATP ligands in the proper execution of ATP site directed inhibitors is essential to obtain secure of the Abl kinase domain for X ray crystallography.