A protein kinase inhibitor is a type of

enzyme inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...

that blocks the action of one or more

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...

s. Protein kinases are enzymes that

phosphorylate In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

(add a

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

, or PO₄, group) to a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

and can modulate its function. The phosphate groups are usually added to serine, threonine, or tyrosine

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s on the protein: most kinases act on both serine and threonine, the

tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...

s act on tyrosine, and a number (

dual-specificity kinase In biochemistry, a dual-specificity kinase () is a kinase that can act as both tyrosine kinase and serine/threonine kinase. MEKs, involved in MAP pathways, are principal examples of dual-specificity kinases. Other common examples include: * AD ...

s) act on all three. There are also protein kinases that phosphorylate other amino acids, including

histidine kinase Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are homod ...

s that phosphorylate histidine residues. Phosphorylation regulates many biological processes, and protein kinase inhibitors can be used to treat diseases due to hyperactive protein kinases (including mutant or overexpressed kinases in cancer) or to modulate cell functions to overcome other disease drivers.

Clinical use

Kinase inhibitors such as

dasatinib Dasatinib, sold under the brand name Sprycel among others, is a targeted therapy medication used to treat certain cases of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Specifically it is used to treat cases that ar ...

are often used in the treatment of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

and

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

. Some of the kinase inhibitors used in treating cancer are inhibitors of

s. The effectiveness of kinase inhibitors on various cancers can vary from patient to patient.

Examples

There are several drugs launched or in development that target protein kinases and the receptors that activate them:

Comparison of available agents

Note:
AD = Approval date.
MS = Myelosuppression.
D = Diarrhoea.
FR = Fluid retention.
As far as myelosuppression, diarrhoea and fluid retention goes: +++ means >70% of patients exhibit clinically significant myelosuppression. ++ means 30-70% of patients exhibit significant myelosuppression. + means 10-30% of patients exhibit significant myelosuppression. - means 0-10% of patients exhibit this side effect.
General references templates are given, which refer the reader to the respective drug database.

References

External links

* Ayala-Aguilera, C. C.; Valero, T.; Lorente-Macías, Á.; Baillache, D. J.; Croke, S.; Unciti-Broceta, A
Small Molecule Kinase Inhibitor Drugs (1995–2021): Medical Indication, Pharmacology, and Synthesis
J. Med. Chem. 2021.
PKIDB: A searchable database of kinase inhibitors in clinical trials containing physicochemical properties and structures, protein kinase targets, therapeutic indications, year of first approval, and trade names
* *

* in *Attwood, Misty M; Fabbro, Doriano; Sokolov, Aleksandr V; Knapp, Stephan;, Schiöth, Helgi B. (2021) Trends in kinase drug discovery: targets, indications and inhibitor design. Nat Rev Drug Discov. doi
10.1038/s41573-021-00252-y
PMI
34354255
*A list of US FDA-approved small molecule protein kinase inhibitors, their protein kinase targets, therapeutic indications, and links to the FDA label are provided a

Roskoski, R. Jr. (2021) Properties of FDA-approved small molecule protein kinase inhibitors: A 2021 update. Pharmacol Res.165:105463. do
10.1016/j.phrs.2021.105463
PMI
33513356
{{Chemotherapeutic agents

Clinical use

Examples

Comparison of available agents

See also

References

External links