Where to find compounds IC50 on an enzyme?

Question

I am looking for half maximal inhibitory concentration (IC50) values on a enzyme.

I already searched through ChemBL, PubChem and BindingDB. The three seem to give consistent results.

However, looking in the literature, there are lots of compounds which are not in these databases. These later may provide higher level of curation. I am still interested in the data available in literature. Any other available repository or text mining approach will be great.

Answer 1

To my knowledge, there are no data bases accumulating half maximal inhibitory concentration values on a enzyme ($\mathrm{IC_{50}}$). According to Wikipedia:

Half maximal inhibitory concentration ($\mathrm{IC_{50}}$) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function (i.e. an enzyme, cell, cell receptor, microorganism, etc.).

$\mathrm{IC_{50}}$ is commonly used as a measure of antagonist drug potency in pharmacological research. According to the FDA, $\mathrm{IC_{50}}$ represents the concentration of a drug that is required for 50% inhibition in vitro. It is comparable to an $\mathrm{EC_{50}}$ for agonist drugs.

The major reason for not to accumulate $\mathrm{IC_{50}}$ values is their abundance. For example, for given specific enzyme, there may be vast number of inhibitors present. All of these inhibitors have their specific $\mathrm{IC_{50}}$ value. Thus, if you need to find a $\mathrm{IC_{50}}$ value of specific inhibitor on a particular protein (or enzyme) or a receptor or other biological system, you should search using both names of the inhibitor and biological system as key words. Thus, you would find any literature, which may have $\mathrm{IC_{50}}$ values for sought combination.

For example, Galectin-3 is a protein that is a member of the lectin family (carbohydrate-binding proteins). Galectin-3 is approximately $\pu{30 kDa}$, and contains a carbohydrate-recognition-binding domain with about 130 amino acids that enable the specific binding of $\beta$-galactosides, such as N-acetyllactosamine (14; the parent substrate; $\mathrm{IC_{50}} = \pu{158 \mu M}$ under the conditions; see insert red box). Several derivatives of N-acetyllactosamine (15 - 18) have displayed inhibitory activities with different $\mathrm{IC_{50}}$ values ranging from $13$ to $\pu{31 \mu M}$ (See the plot below):

On the other hand one inhibitor can be active against more than one biological systems with different $\mathrm{IC_{50}}$ values.

Relevant References:

1. P. Sörme, B. Kahl-Knutsson, U. Wellmar, B.-G. Magnusson, H. Leffler, U. J. Nilsson, “[12] Design and Synthesis of Galectin Inhibitors,” In Methods in Enzymology, Volume 363 – Recognition of Carbohydrates in Biological Systems, Part B: Special Applications; Y. C. Lee and R. C. Lee, Eds.; Academic Press: Amsterdam, The Netherlands, 2003, pp. 157–169.
2. P. Sörme, Y. Qian, Per‐G. Nyholm, H. Leffler, U. J. Nilsson, “Low micromolar inhibitors of galectin-3 based on 3'-derivatization of N-acetyllactosamine,” ChemBio Chem 2002, 3(2-3), 183–189 (https://doi.org/10.1002/1439-7633(20020301)3:2/3<183::AID-CBIC183>3.0.CO;2-%23).
3. J. Hynes, Jr., S. K. Nair, “Chapter Nine - Advances in the Discovery of Small-Molecule IRAK4 Inhibitors,” Annual Reports in Medicinal Chemistry 2014, 49(1), 117–133 (https://doi.org/10.1016/B978-0-12-800167-7.00009-2).