IC50

CAS Registry Number Molecular formula R Penase IC50, llg/mL " TEMail) Cephase Refs. 

Ligand CAS Registry Number Stmcture number DOCK rank IC50, mM DOCK a score... 

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

It can be seen from Equation 3.38 that unknown variation in gpl20 levels can lead to differences in the correction factor between the experimentally observed IC50 and the desired quantity K4. However, this variation is minimal if low levels of control signal are used for screening (i.e., minimal concentration of CD4 is used to gain an acceptable signal to noise ratio). 

FIGURE 4.11 Relationship between the observed IC50 for allosteric antagonists and the amount of radioligand present in the assay according to Equation 4.13. Dotted line shows relationship for a competitive antagonist. 

A concentration of displacing ligand that produces a 50% decrease in p is defined as the IC50. The following relation can be defined ... 

From this, the relationship between the IC50 and the amount of tracer ligand [A ] is defined as [2]... 

Relationship Between IC50 (itid Kifor Allosteric Antagonists... 

The concentration of allosteric antagonist [B] that reduces a signal from a bound amount [A ] of radioligand by 50% is defined as the IC50 ... 

Equation 6.19 predicts an increasing IC50 with either increases in L or 1. In systems with low-efficacy inverse agonists or in systems with low levels of constitutive activity, the observed location parameter is still a close estimate of the KB (equilibrium dissociation constant of the ligand-receptor complex, a molecular quantity that transcends test system type). In general, the observed potency of inverse agonists only defines the lower limit of affinity. 

Short-form measures of activity—potency ratios for agonists, apparent KB values (pA2, IC50)—for... 

Surmountable antagonism can be quantified by pA2 values. Insurmountable antagonism through IC50 values that in some cases can be corrected for the strength of stimulation in the system. 

The middle of the concentration range should be as near to the location parameter (i.e., EC50, IC50) of the curve as possible. 

It can be seen that the IC50 increases with increasing values of [A ]/Kd in accordance with simple competitive antagonism. This can be tested by comparison of the data to the Cheng-Prusoff equation (Equation 4.12). The data in Table 12.2b... 

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