Src inhibitor

A Src inhibitor is a protein kinase inhibitor that inhibits the tyrosine kinase Src .

properties

The tyrosine kinase Src (from English sarcoma ) is an oncogene that is involved in the malignant transformation of cells . Inhibiting this protein kinase is therefore a form of treatment in cancer therapy . As with most cancer therapies, resistance can develop when used , which is why combination therapies are being investigated to avoid the formation of resistance by increasing the selection pressure . Protein kinase inhibitors are used depending on the cell type and genome of the particular tumor.

Examples

Ponatinib

KX2-391 is orally bioavailable and has a GI ₅₀ of 9 to 60 nM in cancer cell lines .
Bosutinib
Ponatinib
Saracatinib
PP1 and PP2 are inhibitors of the tyrosine kinases Lck and FynT .
Quercetin
Dasatinib

literature

A. Aleshin, RS Finn: SRC: a century of science brought to the clinic. In: Neoplasia . Volume 12, Number 8, August 2010, pp. 599-607, ISSN 1476-5586 . PMID 20689754 . PMC 2915404 (free full text).
NA Chatzizacharias, GP Kouraklis, CT Giaginis, SE Theocharis: Clinical significance of Src expression and activity in human neoplasia. In: Histology and histopathology. Volume 27, Number 6, June 2012, pp. 677-692, ISSN 1699-5848 . PMID 22473690 .

Individual evidence

↑ H. Creedon, VG Brunton: Src kinase inhibitors: promising cancer therapeutics? In: Critical reviews in oncogenesis. Volume 17, Number 2, 2012, pp. 145-159, ISSN 0893-9675 . PMID 22471705 .
↑ B. Elsberger, B. Stewart, O. Tatarov, J. Edwards: Is Src a viable target for Treating Tumors solid? In: Current Cancer Drug Targets . Volume 10, Number 7, November 2010, pp. 683-694, ISSN 1873-5576 . PMID 20578988 .
↑ LN Puls, M. Eadens, W. Messersmith: Current status of SRC inhibitors in solid tumor malignancies. In: The Oncologist . Volume 16, Number 5, 2011, pp. 566-578, ISSN 1549-490X . doi : 10.1634 / theoncologist.2010-0408 . PMID 21521831 . PMC 3228195 (free full text).
^ R. Krishnamurty, DJ Maly: Biochemical mechanisms of resistance to small-molecule protein kinase inhibitors. In: ACS Chemical Biology . Volume 5, Number 1, January 2010, pp. 121-138, ISSN 1554-8937 . doi : 10.1021 / cb9002656 . PMID 20044834 . PMC 2879594 (free full text).
↑ S. Hiscox, P. Barrett-Lee, AC Borley, RI Nicholson: Combining Src inhibitors and aromatase inhibitors: a novel strategy for overcoming endocrine resistance and bone loss. In: European Journal of Cancer (Oxford, England: 1990). Volume 46, Number 12, August 2010, pp. 2187-2195, ISSN 1879-0852 . doi : 10.1016 / j.ejca.2010.04.012 . PMID 20471823 .
↑ PA Jänne, N. Gray, J. Settleman: Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. In: Nature Reviews Drug Discovery . Volume 8, Number 9, September 2009, pp. 709-723, ISSN 1474-1784 . doi : 10.1038 / nrd2871 . PMID 19629074 .
↑ PA Ott, S. Adams: Small-molecule protein kinase inhibitors and their effects on the immune system: implications for cancer treatment. In: Immunotherapy. Volume 3, Number 2, February 2011, pp. 213-227, ISSN 1750-7448 . doi : 10.2217 / imt.10.99 . PMID 21322760 .
↑ W. Jeong, JH Doroshow, p kummar: United States Food and Drug Administration approved oral kinase inhibitors for the treatment of malignancies. In: Current Problems in Cancer . Volume 37, Number 3, 2013 May-Jun, pp. 110-144, ISSN 1535-6345 . doi : 10.1016 / j.currproblcancer.2013.06.001 . PMID 23972982 . PMC 3761410 (free full text).
↑ Antonarakis ES, Heath EI, Posadas EM, Yu EY et al .: A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer . In: Cancer Chemother Pharmacol . 71, No. 4, Apr 2013, pp. 883-892. doi : 10.1007 / s00280-013-2079-z .
↑ HJ Nam, SA Im, DY Oh, P. Elvin, HP Kim, YK Yoon, A. Min, SH Song, SW Han, TY Kim, YJ Bang: Antitumor activity of saracatinib (AZD0530), a c-Src / Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer. In: Molecular Cancer Therapeutics . Volume 12, Number 1, January 2013, pp. 16-26, ISSN 1538-8514 . doi : 10.1158 / 1535-7163.MCT-12-0109 . PMID 23144237 .

[1] H. Creedon, VG Brunton: Src kinase inhibitors: promising cancer therapeutics? In: Critical reviews in oncogenesis. Volume 17, Number 2, 2012, pp. 145-159, ISSN 0893-9675 . PMID 22471705 .

[2] B. Elsberger, B. Stewart, O. Tatarov, J. Edwards: Is Src a viable target for Treating Tumors solid? In: Current Cancer Drug Targets . Volume 10, Number 7, November 2010, pp. 683-694, ISSN 1873-5576 . PMID 20578988 .

[3] LN Puls, M. Eadens, W. Messersmith: Current status of SRC inhibitors in solid tumor malignancies. In: The Oncologist . Volume 16, Number 5, 2011, pp. 566-578, ISSN 1549-490X . doi : 10.1634 / theoncologist.2010-0408 . PMID 21521831 . PMC 3228195 (free full text).

[4] R. Krishnamurty, DJ Maly: Biochemical mechanisms of resistance to small-molecule protein kinase inhibitors. In: ACS Chemical Biology . Volume 5, Number 1, January 2010, pp. 121-138, ISSN 1554-8937 . doi : 10.1021 / cb9002656 . PMID 20044834 . PMC 2879594 (free full text).

[5] S. Hiscox, P. Barrett-Lee, AC Borley, RI Nicholson: Combining Src inhibitors and aromatase inhibitors: a novel strategy for overcoming endocrine resistance and bone loss. In: European Journal of Cancer (Oxford, England: 1990). Volume 46, Number 12, August 2010, pp. 2187-2195, ISSN 1879-0852 . doi : 10.1016 / j.ejca.2010.04.012 . PMID 20471823 .

[6] PA Jänne, N. Gray, J. Settleman: Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. In: Nature Reviews Drug Discovery . Volume 8, Number 9, September 2009, pp. 709-723, ISSN 1474-1784 . doi : 10.1038 / nrd2871 . PMID 19629074 .

[7] PA Ott, S. Adams: Small-molecule protein kinase inhibitors and their effects on the immune system: implications for cancer treatment. In: Immunotherapy. Volume 3, Number 2, February 2011, pp. 213-227, ISSN 1750-7448 . doi : 10.2217 / imt.10.99 . PMID 21322760 .

[8] W. Jeong, JH Doroshow, p kummar: United States Food and Drug Administration approved oral kinase inhibitors for the treatment of malignancies. In: Current Problems in Cancer . Volume 37, Number 3, 2013 May-Jun, pp. 110-144, ISSN 1535-6345 . doi : 10.1016 / j.currproblcancer.2013.06.001 . PMID 23972982 . PMC 3761410 (free full text).

[9] Antonarakis ES, Heath EI, Posadas EM, Yu EY et al .: A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer . In: Cancer Chemother Pharmacol . 71, No. 4, Apr 2013, pp. 883-892. doi : 10.1007 / s00280-013-2079-z .

[10] HJ Nam, SA Im, DY Oh, P. Elvin, HP Kim, YK Yoon, A. Min, SH Song, SW Han, TY Kim, YJ Bang: Antitumor activity of saracatinib (AZD0530), a c-Src / Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer. In: Molecular Cancer Therapeutics . Volume 12, Number 1, January 2013, pp. 16-26, ISSN 1538-8514 . doi : 10.1158 / 1535-7163.MCT-12-0109 . PMID 23144237 .