Research ExplorerPublicationsLight-controlled inhibition of BRAFV600E kinase

Light-controlled inhibition of BRAFV600E kinase

Standard

Light-controlled inhibition of BRAFV600E kinase. / Hoorens, Mark W H; Ourailidou, Maria E; Rodat, Theo; van der Wouden, Petra E; Kobauri, Piermichele; Kriegs, Malte; Peifer, Christian; Feringa, Ben L; Dekker, Frank J; Szymanski, Wiktor.

In: EUR J MED CHEM, Vol. 179, 01.10.2019, p. 133-146.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hoorens, MWH, Ourailidou, ME, Rodat, T, van der Wouden, PE, Kobauri, P, Kriegs, M, Peifer, C, Feringa, BL, Dekker, FJ & Szymanski, W 2019, 'Light-controlled inhibition of BRAFV600E kinase', EUR J MED CHEM, vol. 179, pp. 133-146. https://doi.org/10.1016/j.ejmech.2019.06.042

APA

Hoorens, M. W. H., Ourailidou, M. E., Rodat, T., van der Wouden, P. E., Kobauri, P., Kriegs, M., Peifer, C., Feringa, B. L., Dekker, F. J., & Szymanski, W. (2019). Light-controlled inhibition of BRAFV600E kinase. EUR J MED CHEM, 179, 133-146. https://doi.org/10.1016/j.ejmech.2019.06.042

Vancouver

Hoorens MWH, Ourailidou ME, Rodat T, van der Wouden PE, Kobauri P, Kriegs M et al. Light-controlled inhibition of BRAFV600E kinase. EUR J MED CHEM. 2019 Oct 1;179:133-146. https://doi.org/10.1016/j.ejmech.2019.06.042

Bibtex

@article{e3877ba1fbe24ef28d965d3dcdb40b27,
title = "Light-controlled inhibition of BRAFV600E kinase",
abstract = "Metastatic melanoma is amongst the most difficult types of cancer to treat, with current therapies mainly relying on the inhibition of the BRAFV600E mutant kinase. However, systemic inhibition of BRAF by small molecule drugs in cancer patients results - paradoxically - in increased wild-type BRAF activity in healthy tissue, causing side-effects and even the formation of new tumors. Here we show the development of BRAFV600E kinase inhibitors of which the activity can be switched on and off reversibly with light, offering the possibility to overcome problems of systemic drug activity by selectively activating the drug at the desired site of action. Based on a known inhibitor, eight photoswitchable effectors containing an azobenzene photoswitch were designed, synthesized and evaluated. The most promising inhibitor showed an approximately 10-fold increase in activity upon light-activation. This research offers inspiration for the development of therapies for metastatic melanoma in which tumor tissue is treated with an active BRAFV600E inhibitor with high spatial and temporal resolution, thus limiting the damage to other tissues.",
author = "Hoorens, {Mark W H} and Ourailidou, {Maria E} and Theo Rodat and {van der Wouden}, {Petra E} and Piermichele Kobauri and Malte Kriegs and Christian Peifer and Feringa, {Ben L} and Dekker, {Frank J} and Wiktor Szymanski",
note = "Copyright {\textcopyright} 2019 Elsevier Masson SAS. All rights reserved.",
year = "2019",
month = oct,
day = "1",
doi = "10.1016/j.ejmech.2019.06.042",
language = "English",
volume = "179",
pages = "133--146",
journal = "EUR J MED CHEM",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

RIS

TY - JOUR

T1 - Light-controlled inhibition of BRAFV600E kinase

AU - Hoorens, Mark W H

AU - Ourailidou, Maria E

AU - Rodat, Theo

AU - van der Wouden, Petra E

AU - Kobauri, Piermichele

AU - Kriegs, Malte

AU - Peifer, Christian

AU - Feringa, Ben L

AU - Dekker, Frank J

AU - Szymanski, Wiktor

N1 - Copyright © 2019 Elsevier Masson SAS. All rights reserved.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Metastatic melanoma is amongst the most difficult types of cancer to treat, with current therapies mainly relying on the inhibition of the BRAFV600E mutant kinase. However, systemic inhibition of BRAF by small molecule drugs in cancer patients results - paradoxically - in increased wild-type BRAF activity in healthy tissue, causing side-effects and even the formation of new tumors. Here we show the development of BRAFV600E kinase inhibitors of which the activity can be switched on and off reversibly with light, offering the possibility to overcome problems of systemic drug activity by selectively activating the drug at the desired site of action. Based on a known inhibitor, eight photoswitchable effectors containing an azobenzene photoswitch were designed, synthesized and evaluated. The most promising inhibitor showed an approximately 10-fold increase in activity upon light-activation. This research offers inspiration for the development of therapies for metastatic melanoma in which tumor tissue is treated with an active BRAFV600E inhibitor with high spatial and temporal resolution, thus limiting the damage to other tissues.

AB - Metastatic melanoma is amongst the most difficult types of cancer to treat, with current therapies mainly relying on the inhibition of the BRAFV600E mutant kinase. However, systemic inhibition of BRAF by small molecule drugs in cancer patients results - paradoxically - in increased wild-type BRAF activity in healthy tissue, causing side-effects and even the formation of new tumors. Here we show the development of BRAFV600E kinase inhibitors of which the activity can be switched on and off reversibly with light, offering the possibility to overcome problems of systemic drug activity by selectively activating the drug at the desired site of action. Based on a known inhibitor, eight photoswitchable effectors containing an azobenzene photoswitch were designed, synthesized and evaluated. The most promising inhibitor showed an approximately 10-fold increase in activity upon light-activation. This research offers inspiration for the development of therapies for metastatic melanoma in which tumor tissue is treated with an active BRAFV600E inhibitor with high spatial and temporal resolution, thus limiting the damage to other tissues.

U2 - 10.1016/j.ejmech.2019.06.042

DO - 10.1016/j.ejmech.2019.06.042

M3 - SCORING: Journal article

C2 - 31252305

VL - 179

SP - 133

EP - 146

JO - EUR J MED CHEM

JF - EUR J MED CHEM

SN - 0223-5234

ER -