Protein kinase inhibitor

Short description: Enzymes that block actions of protein kinases

A protein kinase inhibitor (PKI) is a type of enzyme inhibitor that blocks the action of one or more protein kinases.[1][2] Protein kinases are enzymes that phosphorylate (add a phosphate, or PO4, group) to a protein and can modulate its function.[3]

The phosphate groups are usually added to serine, threonine, or tyrosine amino acids on the protein. Most kinases act on both serine and threonine, the tyrosine kinases act on tyrosine, and a number (dual-specificity kinases) act on all three. There are also protein kinases that phosphorylate other amino acids, including histidine kinases that phosphorylate histidine residues.[4]

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.

## Contents

* 1 Clinical use
* 2 Examples
* 3 Comparison of available agents
* 4 See also
* 5 References
* 6 Further reading
* 7 External links

## Clinical use

Kinase inhibitors such as dasatinib are often used in the treatment of cancer and inflammation.[5]

Some of the kinase inhibitors used in treating cancer are inhibitors of tyrosine kinases.[6] The effectiveness of kinase inhibitors on various cancers can vary from patient to patient.[7]

## Examples

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

Name | Target | Company | Class | FDA approval

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Adavosertib | WEE1 | AstraZeneca | Small molecule |
Afatinib | EGFR/ErbB2 | Boehringer Ingelheim | Small molecule | 2013 Non-small cell lung cancer
Axitinib | VEGFR1/VEGFR2/VEGFR3/PDGFRB/c-KIT | Pfizer | Small molecule | 2012 Renal cell carcinoma
Bosutinib | Bcr-Abl / SRC | Pfizer | Small molecule | 2012 Chronic myelogenous leukemia
Cetuximab | EGFR | Imclone / BMS | Monoclonal antibody | 2006 Mar (SCCHN)
Cobimetinib | MEK | Exelixis / Genentech-Roche | Small molecule | 2015 Nov (Advanced melanoma with BRAF mutation) in Combination with Vemurafenib (BRAF)
Crizotinib | ALK/Met | Pfizer | Small molecule | 2011 Aug (NSCLC with Alk mutation)
Cabozantinib | RET/MET/VEGFR2 | Exelixis | Small molecule | 2012 Nov (Metastatic medullary thyroid cancer)
Dacomitinib | EGFR/ErbB2/ErbB4 | Pfizer | Small molecule | 2018 Non-small cell lung cancer
Dasatinib | multiple targets | BMS | Small molecule | 2006
Entrectinib | TrkA/TrkB/TrkC/ROS1/ALK | Ignyta | Small molecule | 2004
Erdafitinib | FGFR | Janssen | Small molecule | 2019
Erlotinib | EGFR | Genentech | Small molecule | 2004
Fostamatinib | Syk | Rigel Pharmaceuticals / AstraZeneca | Small molecule |
Gefitinib | EGFR | AstraZeneca | Small molecule | 2003 non-small cell lung cancer (NSCLC)
Ibrutinib | BTK | Pharmacyclics | Small molecule | 2013
Imatinib | Bcr-Abl | Novartis | Small molecule | 2001 (CML), 2002 (GIST) [8]
Lapatinib | EGFR/ErbB2 | GSK | Small molecule | 2007 (HER2+ Breast)
Lenvatinib | VEGFR2 | Eisai Co. | Small molecule | 2015 (thyroid), 2016 (renal)
Mubritinib | ? | Takeda | Small molecule |
Nilotinib | Bcr-Abl | Novartis | Small molecule | 2007
Pazopanib | VEGFR2/PDGFR/c-kit | GlaxoSmithKline | Small molecule | 2009 (RCC)
Pegaptanib | VEGF | OSI/ Pfizer | RNA Aptamer | 2004 (AMD)
Ruxolitinib | JAK | Incyte | Small molecule | 2011 (Myelofibrosis)
Sorafenib | multiple targets | Onyx / Bayer | Small molecule | 2005 Dec (kidney)
Sunitinib | multiple targets | SUGEN / Pfizer | Small molecule | 2006 Jan (RCC & GIST)
SU6656 | Src, others | SUGEN | Small molecule |
Tucatinib | HER2 | Seattle Genetics | Small molecule | 2020
Vandetanib | RET/VEGFR/EGFR | AstraZeneca | Small molecule | 2011
Vemurafenib | BRAF | Roche | Small molecule | 2011 Aug (Advanced melanoma with BRAF mutation)

## Comparison of available agents

Comparison of available agents used as Human Medicines Drug | Sponsor | Target | Indications | Major toxicities | Black box warning(s) | MS
[Note 1][9] | D | FR | PC (AU)
[Note 2] | PC (US)
[Note 2] | FDA AD[10] | \-  | Afatinib | Boehringer Ingelheim | ErbB family (irreversible) | Advanced non-small cell lung cancer | Hepatotoxicity, kidney failure, electrolyte anomalies (mostly hypokalaemia) and interstitial lung disease (uncommon). | None | - | +++ | - | C | D | 12 July 2013 | 25 September 2013 | 7 November 2013

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Aflibercept | Bayer, Regeneron Pharmaceuticals | VEGF | Advanced colorectal cancer and wet macular degeneration. | GI perforation, haemorrhage and hepatotoxicity | None | +++/++ | +++/++ | - | D | C | 21 November 2011 | 22 November 2012 | 2 April 2013
Axitinib | Pfizer | VEGFR, PDGFR, c-KIT | Renal cell carcinoma | Thyroid dysfunction, blood clots, haemorrhages, reversible posterior leucoencephalopathy syndrome (uncommon), GI perforation/fistula (uncommon) and electrolyte disturbances | None | ++ | ++ | - | D | D | 27 January 2012 | 3 September 2012 | 26 July 2012
Bevacizumab | Genentech | VEGF | Colorectal cancer, breast cancer, non-small cell lung cancer, renal cell carcinoma, macular degeneration and glioblastoma | Hypertension, GI perforation, ovarian failure, GI haemorrhage, blood clots, electrolyte anomalies, ileus, congestive heart failure, osteonecrosis of the jaw (rare), necrotising fasciitis (rare), gallbladder perforation (rare) | GI perforation, haemorrhage and wound healing complications | ++ | ++/+ | - | D | C | 26 February 2004 | 12 January 2005 | 24 February 2005
Bosutinib | Pfizer | Bcr-Abl | Second-line Chronic myelogenous leukaemia treatment | Lower respiratory tract infection, anaphylaxis (uncommon), electrolyte anomalies, cardiovascular effects (especially QT interval prolongation), GI haemorrhage (uncommon), hepatotoxicity and kidney failure. | None | ++/+ | +++ | + | N/A | D | 4 September 2012 | 27 March 2013 | N/A
Cabozantinib | Exelixis | c-Met, VEGFR2 | Metastatic thyroid cancer | Electrolyte anomalies, hypotension, peripheral sensory neuropathy, GI perforation/fistula, reversible posterior leucoencephalopathy syndrome (rare), blood clots and osteonecrosis. | GI haemorrhage, perforation and fistula | ++ | +++/++ | - | N/A | D | 29 November 2012 | N/A | N/A
Crizotinib | Pfizer | ALK, HGFR, c-MET | Anaplastic lymphoma kinase-positive non-small cell lung cancer | Peripheral neuropathy, electrolyte anomalies, blood clots, kidney cyst, liver failure, interstitial lung disease and cardiotoxicity (probably QT interval prolongation). | None | ++ | ++ | ++/+ | D | D | 26 August 2011 | 23 October 2012 | 27 September 2013
Dacomitinib | Pfizer | ErbB family (irreversible) | Advanced non-small cell lung cancer | Diarrhea, rash, fatigue. | None | N/A | N/A | N/A | N/A | N/A | 27 September 2018 | 2 April 2019 | \-
Dasatinib | Bristol-Myers Squibb | Bcr-Abl, Src, c-KIT | Second-line Chronic myelogenous leukaemia treatment | Electrolyte disturbances, haemorrhages, fluid retention, heart failure (uncommon), myocardial infarction (uncommon) and pulmonary hypertension | None | +/- | ++ | ++ | D | D | 28 June 2006 | 20 November 2006 | 15 January 2007
Erlotinib | Roche | EGFR | Advanced non-small cell lung cancer and pancreatic cancer | GI bleeds (rare), liver failure (rare), hepatorenal syndrome (rare), EGFR skin reactions and interstitial lung disease(uncommon). | None | - | +++/++ | - | C | D | 18 November 2004 | 19 September 2005 | 30 January 2006
Gefitinib | AstraZeneca, Teva | EGFR | Advanced non-small cell lung cancer with EGFR mutation | Haemorrhage, EGFR skin reactions (including Stevens–Johnson syndrome [SJS; rare] and toxic epidermal necrolysis[TEN; rare]), liver failure (rare), hepatitis (uncommon), pancreatitis (uncommon) and interstitial lung disease (uncommon). | N/A | - | +++/++ | - | C | D | 5 May 2003 (discontinued) | 24 June 2009 | 7 September 2011
Imatinib | Novartis | Bcr-Abl | First-line chronic myelogenous leukaemia treatment | Haemorrhage, electrolyte disturbances, cardiotoxicity (uncommon), kidney failure (uncommon), GI perforation, hepatotoxicity (rare) and rhabdomyolysis (rare) | N/A | +++/++ | + | ++ | D | D | 10 May 2001 | 7 November 2001 | 13 August 2001
Lapatinib | GlaxoSmithKline | HER2 | HER2-positive advanced breast cancer | Hypersensitivity (rare), hepatotoxicity (uncommon), interstitial lung disease (uncommon) and cardiovascular problems. | Hepatotoxicity | - | ++ | - | C | D | 13 March 2007 | 10 June 2008 | 28 June 2007
Nilotinib | Novartis | Bcr-Abl | Second-line chronic myelogenous leukaemia treatment | Hyperglycaemia, electrolyte disturbances, fluid retention, pancreatitis and cardiotoxicity (mostly QT interval prolongation). | QT interval prolongation and electrolyte anomalies | ++ | + | + | D | D | 29 October 2007 | 2 June 2009 | 17 January 2008
Panitumumab | Amgen | EGFR | Colorectal cancer | Electrolyte anomalies, anaphylaxis, blood clots, sepsis and pulmonary fibrosis. | Dermatologic reactions and infusion reactions | - | + | + | C | C | 10 October 2006 | 3 December 2007 | 20 March 2012
Pazopanib | GlaxoSmithKline | VEGFR, PDGFR, c-KIT | Renal cell carcinoma and soft tissue sarcoma | Cardiotoxicity (mostly QT interval prolongation but also heart failure [uncommon]), blood clots, haemorrhage, thyroid anomalies (mostly hypothyroidism), blood glucose anomalies (hypoglycaemia and hyperglycaemia), torsades de pointes (uncommon), hepatotoxicity (uncommon), GI perforation/fistula (uncommon) and reversible posterior leucoencephalopathy syndrome (rare). | Hepatotoxicity | - | ++ | - | D | D | 19 October 2009 | 14 June 2010 | 30 June 2010
Pegaptanib | OSI, Pfizer | VEGF | Wet macular degeneration | Hypertension, cataracts, haemorrhage, vitreous floater, transient ischaemic attack, retinal detachment, diabetes mellitus and urinary tract infection | None | - | +/- | ++ | N/A | B | 17 December 2004 | 31 January 2006 | N/A
Ponatinib | ARIAD Pharmaceuticals | Bcr-Abl, BEGFR, PDGFR, FGFR, EPH, SRC, c-KIT, RET, TIE2, FLT3 | T315I-positive Chronic myelogenous leukaemia and T315I-positive-Acute lymphoblastic leukaemia | Hypertension, pneumonia, urinary tract infection, sepsis, GI haemorrhage, liver failure, cardiovascular problems and blood clots. | Liver failure, blood clots and hepatotoxicity | ++ | + | + | N/A | D | 14 December 2012 | 1 July 2013 | N/A
Ranibizumab | Novartis | VEGF-A | Wet macular degeneration and macular oedema (including diabetic macular oedema) | Haemorrhage (conjunctival, vitreous and injection site), increased intraocular pressure, vitreous detachment and retinal degeneration. | None | - | - | - | D | C | 10 August 2012 | 22 January 2007 | 27 February 2007
Regorafenib | Bayer | RET, VEGFR, PDGFR | Advanced colorectal cancer, gastrointestinal stromal tumours | Electrolyte anomalies, hepatotoxicity, hypotension, haemorrhage, GI fistula, thyroid problems and blood clots. | Hepatotoxicity | +++/++ | ++ | - | D | D | 27 September 2012 | 26 August 2013 | 29 November 2013
Ruxolitinib | Novartis | JAK | Myelofibrosis | Hypercholesterolaemia, urinary tract infection, herpes zoster, tuberculosis and hepatotoxicity | None | +++ | - | - | C | C | 16 November 2011 | 23 August 2012 | 3 July 2013
Sorafenib | Bayer | VEGFR, PDGFR, BRAF, c-KIT, etc. | Advanced Renal cell carcinoma and Hepatocellular carcinoma | Hypertension, peripheral neuropathy, thyroid dysfunction, cardiovascular problems (e.g. QT interval prolongation, heart attack or heart failure), electrolyte anomalies, GI perforation (uncommon), pancreatitis (uncommon), hepatitis (rare), nephrotic syndrome (rare) and reversible posterior leucoencephalopathy syndrome (rare) | None | ++ | ++ | - | D | D | 20 December 2005 | 19 July 2006 | 27 September 2006
Sunitinib | Pfizer | VEGFR, PDGFR | Renal cell carcinoma, GI stromal tumour, pancreatic neuroendocrine tumour | Blood clots, cardiovascular problems (mostly heart failure or left ventricular dysfunction but also QT interval prolongation and torsades de pointes), thyroid dysfunction, electrolyte anomalies, skin reactions (including SJS [rare] and TEN [rare]), liver failure (uncommon) and pancreatitis (uncommon). | Hepatotoxicity | + | ++ | + | D | D | 26 January 2006 | 19 July 2006 | 14 September 2006
Tofacitinib | Pfizer | JAK | Rheumatoid arthritis | Infections and malignancies | Serious infections and malignancies | - | - | - | N/A | C | 6 November 2012 | N/A; refused 26 April 2013 | N/A
Trastuzumab | Genentech | HER2 | Breast cancer (for either metastatic disease or adjuvant treatment), metastatic gastric cancer | Congestive heart failure, depression, pulmonary toxicity, infections and tachycardia (heart high rate) | Pulmonary toxicity, cardiomyopathy and a confusion warning | - | + | + | B2 | D | 25 September 1998 | 28 August 2000 | 14 September 2000
Tucatinib | Seattle Genetics | HER2 | Advanced unresectable or metastatic HER2-positive breast cancer | Diarrhea, hepatotoxicity, embryo-fetal toxicity | None |  |  |  |  |  | April 2020 |  | August 2020
Vandetanib | AstraZeneca | VEGFR, EGFR, RET, BRK | Advanced medullary thyroid cancer | Urinary tract infection, hypertension, QT interval prolongation, electrolyte anomalies, depression, GI perforation and thyroid anomalies | QT interval prolongation | - | ++ | - | D | D | 21 April 2011 | 17 February 2012 | 31 January 2013
Vemurafenib | Roche | BRAF | Metastatic melanoma | Photosensitivity, squamous cell carcinoma and hepatotoxicity | None | - | + | + | D | D | 17 August 2011 | 10 May 2012 | 17 February 2012

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.

1. ↑ Myelosuppression.
2. ↑ 2.0 2.1 PC = Pregnancy category

## See also

* Tyrosine kinase inhibitor

## References

1. ↑ "Protein Kinase Inhibitors", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases), 2012, PMID 31643906, https://www.ncbi.nlm.nih.gov/books/NBK548591/, retrieved 7 January 2025
2. ↑ Elgawish, Mohamed S.; Almatary, Aya M.; Zaitone, Sawsan A.; Salem, Mohamed S. H. (2025). "Leveraging artificial intelligence and machine learning in kinase inhibitor development: advances, challenges, and future prospects" (in en). RSC Medicinal Chemistry 16 (10): 4698–4720. doi:10.1039/D5MD00494B. ISSN 2632-8682. PMID 40919316. PMC 12412618. https://xlink.rsc.org/?DOI=D5MD00494B.
3. ↑ Cheng, Heung-Chin; Qi, Robert Z.; Paudel, Hemant; Zhu, Hong-Jian (13 December 2011). "Regulation and Function of Protein Kinases and Phosphatases" (in en). Enzyme Research 2011: 1–3. doi:10.4061/2011/794089. ISSN 2090-0414. PMID 22195276.
4. ↑ Wolanin, Peter M.; Thomason, Peter A.; Stock, Jeffry B. (25 September 2002). "Histidine protein kinases: key signal transducers outside the animal kingdom". Genome Biology 3 (10): reviews3013.1. doi:10.1186/gb-2002-3-10-reviews3013. ISSN 1474-760X. PMID 12372152.
5. ↑ Gross, Stefan; Rahal, Rami; Stransky, Nicolas; Lengauer, Christoph; Hoeflich, Klaus P. (1 May 2015). "Targeting cancer with kinase inhibitors". Journal of Clinical Investigation 125 (5): 1780–1789. doi:10.1172/JCI76094. PMID 25932675.
6. ↑ "Definition of tyrosine kinase inhibitor - NCI Dictionary of Cancer Terms". http://www.cancer.gov/templates/db_alpha.aspx?CdrID=44833.
7. ↑ Jänne, Pasi A.; Gray, Nathanael; Settleman, Jeff (2009). "Factors underlying sensitivity of cancers to small-molecule kinase inhibitors". Nature Reviews Drug Discovery 8 (9): 709–23. doi:10.1038/nrd2871. PMID 19629074.
8. ↑ Ian, Ingram (6 February 2012). "FDA Grants Imatinib (Gleevec) Full Approval for Adjuvant Treatment of GIST". http://www.cancernetwork.com/gastrointestinal-stromal-tumor/content/article/10165/2028035.
9. ↑ "Medscape Multispecialty – Home page". WebMD. http://reference.medscape.com/medscapetoday.
10. ↑ Monograph
11. ↑ "European Public Assessment Reports". European Medicines Agency. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.jsp&mid=WC0b01ac058001d12. [full citation needed][full citation needed]

## Further reading

* Attwood, Misty M.; Fabbro, Doriano; Sokolov, Aleksandr V.; Knapp, Stefan; Schiöth, Helgi B. (November 2021). "Trends in kinase drug discovery: targets, indications and inhibitor design". Nature Reviews Drug Discovery 20 (11): 839–861. doi:10.1038/s41573-021-00252-y. PMID 34354255.
* Ayala-Aguilera, Cecilia C.; Valero, Teresa; Lorente-Macías, Álvaro; Baillache, Daniel J.; Croke, Stephen; Unciti-Broceta, Asier (27 January 2022). "Small Molecule Kinase Inhibitor Drugs (1995–2021): Medical Indication, Pharmacology, and Synthesis". Journal of Medicinal Chemistry 65 (2): 1047–1131. doi:10.1021/acs.jmedchem.1c00963. PMID 34624192. https://www.pure.ed.ac.uk/ws/files/236370357/Small_molecule_kinase_inhibitor_drugs_1995_2021_Medical_indication_pharmacology_and_synthesis.pdf.
* Carles, Fabrice; Bourg, Stéphane; Meyer, Christophe; Bonnet, Pascal (15 April 2018). "PKIDB: A Curated, Annotated and Updated Database of Protein Kinase Inhibitors in Clinical Trials". Molecules 23 (4): 908. doi:10.3390/molecules23040908. PMID 29662024.
* Jänne, Pasi A.; Gray, Nathanael; Settleman, Jeff (September 2009). "Factors underlying sensitivity of cancers to small-molecule kinase inhibitors". Nature Reviews Drug Discovery 8 (9): 709–723. doi:10.1038/nrd2871. PMID 19629074.
* Roskoski, Robert (March 2021). "Properties of FDA-approved small molecule protein kinase inhibitors: A 2021 update". Pharmacological Research 165. doi:10.1016/j.phrs.2021.105463. PMID 33513356.

## External links

* Protein+kinase+inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)
* 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
* 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 at the Blue Ridge Institute for Medical Research web site.

* v
* t
* e

Pharmacology: enzyme inhibition

Class|

* Competitive inhibition
* Uncompetitive inhibition
* Non-competitive inhibition
* Suicide inhibition
* Mixed inhibition

Substrate|

| Oxidoreductase (EC 1)|

* 1.1 Aldose reductase
* HMG-CoA reductase

* 1.3 5α-Reductase

* 1.4 Monoamine oxidase

* 1.5 Dihydrofolate reductase

* 1.13 Lipoxygenase

* 1.14 Aromatase
* COX-2

* 1.17 Xanthine oxidase
* Ribonucleotide reductase

|

Transferase (EC 2)|

* 2.1 COMT
* Thymidylate synthase

* 2.4 PARP

* 2.5 Dihydropteroate synthetase
* Farnesyltransferase

* 2.6 GABA transaminase

* 2.7 Nucleotidyltransferase
* Integrase
* Reverse transcriptase
* Protein kinase
* Tyrosine kinase
* Janus kinase

Hydrolase (EC 3)|

* 3.1 Phosphodiesterase
* Acetylcholinesterase
* Ribonuclease

* 3.2 Polygalacturonase
* Neuraminidase
* Alpha-glucosidase

* 3.4 Protease: Exopeptidase
* DPP-4
* ACE
* Endopeptidase
* Trypsin
* Renin
* Mixed
* Enkephalinase
* Matrix metalloproteinase
* Oxytocinase

* 3.5 Histone deacetylase
* Beta-lactamase

Lyase (EC 4)|

* 4.1 Dopa decarboxylase

* 4.2 Carbonic anhydrase

Miscellaneous|

* Steroidogenesis inhibitor

* v
* t
* e

Targeted cancer therapy / antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")|

| Receptor tyrosine kinase|

* ErbB: HER1/EGFR (Cetuximab
* Panitumumab)
* HER2/neu (Trastuzumab
* Trastuzumab emtansine)

|

Others for solid tumors|

* EpCAM (Catumaxomab
* Edrecolomab)
* VEGF-A (Bevacizumab)

Leukemia/lymphoma|

* lymphoid: CD20 (Ibritumomab
* Obinutuzumab
* Ofatumumab
* Rituximab
* Tositumomab), CD30 (Brentuximab), CD52 (Alemtuzumab)

* myeloid: CD33 (Gemtuzumab)

Tyrosine kinase inhibitors ("-nib")|

| Receptor tyrosine kinase|

* ErbB: HER1/EGFR (Brigatinib
* Dacomitinib
* Erlotinib
* Gefitinib
* Olmutinib
* Osimertinib
* Rociletinib
* Vandetanib)
* HER1/EGFR and HER2/neu
* Afatinib
* Lapatinib
* Neratinib

* RTK class III: C-kit and PDGFR (Axitinib
* Masitinib
* Pazopanib
* Sorafenib
* Sunitinib
* Toceranib)
* FLT3 (Lestaurtinib)

* VEGFR
* Axitinib
* Cediranib
* Lenvatinib
* Nintedanib
* Pazopanib
* Regorafenib
* Semaxanib
* Sorafenib
* Sunitinib
* Tivozanib
* Toceranib
* Vandetanib

* ALK
* Alectinib
* Brigatinib
* Ceritinib
* Crizotinib

RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2).

|

Non-receptor|

* bcr-abl
* Bosutinib
* Dasatinib
* Imatinib
* Nilotinib
* Ponatinib
* Radotinib

* Src (Bosutinib
* Dasatinib)

* Janus kinase
* Lestaurtinib
* Momelotinib
* Pacritinib
* Ruxolitinib

* MAP2K
* Binimetinib
* Cobimetinib
* Selumetinib
* Trametinib

* EML4-ALK
* Crizotinib
* Entrectinib
* Lorlatinib

* Bruton's
* Acalabrutinib
* Ibrutinib

Other|

* fusion protein against VEGF (Aflibercept)
* proapoptotic peptide against ANXA2 and prohibitin (Adipotide)
* exotoxin against IL-2 (Denileukin diftitox)
* mTOR inhibitors
* Everolimus
* Temsirolimus
* hedgehog inhibitors
* Sonidegib
* Vismodegib
* CDK inhibitor (Palbociclib
* Ribociclib)

* v
* t
* e

Intracellular chemotherapeutic agents / antineoplastic agents (L01)

SPs/MIs
(M phase)|

| Block microtubule assembly|

* Vinca alkaloids (Vinblastine#
* Vincristine#
* Vinflunine§
* Vindesine
* Vinorelbine#)

|

Block microtubule disassembly|

* Taxanes (Cabazitaxel
* Docetaxel#
* Larotaxel
* Ortataxel†
* Paclitaxel#
* Tesetaxel)
* Epothilones (Ixabepilone)

DNA replication
inhibitor|

| DNA precursors/
antimetabolites
(S phase)|

| Folic acid|

* Dihydrofolate reductase inhibitor (Aminopterin
* Methotrexate#
* Pemetrexed
* Pralatrexate)
* Thymidylate synthase inhibitor (Raltitrexed
* Pemetrexed)

|

Purine|

* Adenosine deaminase inhibitor (Pentostatin)

* Halogenated/ribonucleotide reductase inhibitors (Cladribine
* Clofarabine
* Fludarabine)
* Nelarabine

* Thiopurine (Tioguanine#
* Mercaptopurine#)

Pyrimidine|

* Thymidylate synthase inhibitor (Fluorouracil#
* Capecitabine#
* Doxifluridine
* Tegafur (+gimeracil/oteracil)
* Carmofur
* Floxuridine)

* DNA polymerase inhibitor (Cytarabine#)

* Ribonucleotide reductase inhibitor (Gemcitabine#)

* Hypomethylating agent (Azacitidine
* Decitabine)

Deoxyribonucleotide|

* Ribonucleotide reductase inhibitor (Hydroxycarbamide#)

Topoisomerase inhibitors
(S phase)|

| I|

* Camptotheca (Camptothecin
* Cositecan†
* Belotecan
* Gimatecan
* Exatecan
* Irinotecan#
* Lurtotecan‡
* Silatecan§
* Topotecan
* Rubitecan‡)

|

II|

* Podophyllum (Etoposide#
* Teniposide)

II+Intercalation|

* Anthracyclines (Aclarubicin
* Daunorubicin#
* Doxorubicin#
* Epirubicin
* Idarubicin
* Amrubicin†
* Pirarubicin
* Valrubicin
* Zorubicin)
* Anthracenediones (Mitoxantrone
* Pixantrone)

Crosslinking of DNA
(CCNS)|

| Alkylating|

* Nitrogen mustards: Chlormethine
* Cyclophosphamide# (Ifosfamide#
* Trofosfamide)
* Chlorambucil# (Melphalan
* Prednimustine)
* Bendamustine#
* Uramustine

* Nitrosoureas: Carmustine
* Lomustine (Semustine)
* Fotemustine
* Nimustine
* Ranimustine
* Streptozocin

* Alkyl sulfonates: Busulfan (Mannosulfan
* Treosulfan)

* Aziridines: Carboquone
* Thiotepa
* Triaziquone
* Triethylenemelamine

|

Platinum-based|

* Carboplatin#
* Cisplatin#
* Dicycloplatin
* Nedaplatin
* Oxaliplatin#
* Satraplatin

Nonclassical|

* Hydrazines (Procarbazine#)
* Triazenes (Dacarbazine#
* Temozolomide)
* Altretamine
* Mitobronitol
* Pipobroman

Intercalation|

* Streptomyces (Actinomycin#
* Bleomycin#
* Mitomycins
* Plicamycin)

Photosensitizers/PDT|

* Aminolevulinic acid / Methyl aminolevulinate
* Efaproxiral
* Porphyrin derivatives (Porfimer sodium
* Talaporfin
* Temoporfin
* Verteporfin)

Other|

| Enzyme inhibitors|

* FI (Tipifarnib§)
* CDK inhibitors (Abemaciclib
* Alvocidib†
* Palbociclib
* Ribociclib
* Seliciclib†)
* PrI
* Bortezomib
* Carfilzomib
* Ixazomib
* PhI (Anagrelide)
* IMPDI (Tiazofurin§)
* LI (Masoprocol)
* PARP inhibitor (Niraparib
* Olaparib
* Rucaparib)
* HDAC (Belinostat
* Panobinostat
* Romidepsin
* Vorinostat)
* PIKI (Idelalisib)

|

Receptor antagonists|

* ERA (Atrasentan)
* Retinoid X receptor (Bexarotene)
* Sex steroid (Testolactone)

Other/ungrouped|

* Amsacrine
* Trabectedin
* Retinoids (Alitretinoin
* Tretinoin#)
* Arsenic trioxide
* Asparagine depleters (Asparaginase#/Pegaspargase)
* Celecoxib
* Demecolcine
* Elesclomol§
* Elsamitrucin
* Estramustine phosphate
* Etoglucid
* Lonidamine
* Lucanthone
* Mitoguazone
* Mitotane
* Oblimersen†
* Omacetaxine mepesuccinate
* Eribulin

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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Original source: https://en.wikipedia.org/wiki/Protein kinase inhibitor. Read more

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