Aarhus University Seal / Aarhus Universitets segl

Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia. / Marchesini, Matteo; Gherli, Andrea; Montanaro, Anna; Patrizi, Laura; Sorrentino, Claudia; Pagliaro, Luca; Rompietti, Chiara; Kitara, Samuel; Heit, Sabine; Olesen, Claus E.; Møller, Jesper V.; Savi, Monia; Bocchi, Leonardo; Vilella, Rocchina; Rizzi, Federica; Baglione, Marilena; Rastelli, Giorgia; Loiacono, Caterina; La Starza, Roberta; Mecucci, Cristina; Stegmaier, Kimberly; Aversa, Franco; Stilli, Donatella; Lund Winther, Anne Marie; Sportoletti, Paolo; Bublitz, Maike; Dalby-Brown, William; Roti, Giovanni.

I: Cell Chemical Biology, Bind 27, Nr. 6, 06.2020, s. 678-697.e13.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Marchesini, M, Gherli, A, Montanaro, A, Patrizi, L, Sorrentino, C, Pagliaro, L, Rompietti, C, Kitara, S, Heit, S, Olesen, CE, Møller, JV, Savi, M, Bocchi, L, Vilella, R, Rizzi, F, Baglione, M, Rastelli, G, Loiacono, C, La Starza, R, Mecucci, C, Stegmaier, K, Aversa, F, Stilli, D, Lund Winther, AM, Sportoletti, P, Bublitz, M, Dalby-Brown, W & Roti, G 2020, 'Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia', Cell Chemical Biology, bind 27, nr. 6, s. 678-697.e13. https://doi.org/10.1016/j.chembiol.2020.04.002

APA

Marchesini, M., Gherli, A., Montanaro, A., Patrizi, L., Sorrentino, C., Pagliaro, L., Rompietti, C., Kitara, S., Heit, S., Olesen, C. E., Møller, J. V., Savi, M., Bocchi, L., Vilella, R., Rizzi, F., Baglione, M., Rastelli, G., Loiacono, C., La Starza, R., ... Roti, G. (2020). Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia. Cell Chemical Biology, 27(6), 678-697.e13. https://doi.org/10.1016/j.chembiol.2020.04.002

CBE

Marchesini M, Gherli A, Montanaro A, Patrizi L, Sorrentino C, Pagliaro L, Rompietti C, Kitara S, Heit S, Olesen CE, Møller JV, Savi M, Bocchi L, Vilella R, Rizzi F, Baglione M, Rastelli G, Loiacono C, La Starza R, Mecucci C, Stegmaier K, Aversa F, Stilli D, Lund Winther AM, Sportoletti P, Bublitz M, Dalby-Brown W, Roti G. 2020. Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia. Cell Chemical Biology. 27(6):678-697.e13. https://doi.org/10.1016/j.chembiol.2020.04.002

MLA

Vancouver

Marchesini M, Gherli A, Montanaro A, Patrizi L, Sorrentino C, Pagliaro L o.a. Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia. Cell Chemical Biology. 2020 jun;27(6):678-697.e13. https://doi.org/10.1016/j.chembiol.2020.04.002

Author

Marchesini, Matteo ; Gherli, Andrea ; Montanaro, Anna ; Patrizi, Laura ; Sorrentino, Claudia ; Pagliaro, Luca ; Rompietti, Chiara ; Kitara, Samuel ; Heit, Sabine ; Olesen, Claus E. ; Møller, Jesper V. ; Savi, Monia ; Bocchi, Leonardo ; Vilella, Rocchina ; Rizzi, Federica ; Baglione, Marilena ; Rastelli, Giorgia ; Loiacono, Caterina ; La Starza, Roberta ; Mecucci, Cristina ; Stegmaier, Kimberly ; Aversa, Franco ; Stilli, Donatella ; Lund Winther, Anne Marie ; Sportoletti, Paolo ; Bublitz, Maike ; Dalby-Brown, William ; Roti, Giovanni. / Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia. I: Cell Chemical Biology. 2020 ; Bind 27, Nr. 6. s. 678-697.e13.

Bibtex

@article{d2d171f084e24c7eba5d51efb72ded40,
title = "Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia",
abstract = "The identification of SERCA (sarco/endoplasmic reticulum calcium ATPase) as a target for modulating gain-of-function NOTCH1 mutations in Notch-dependent cancers has spurred the development of this compound class for cancer therapeutics. Despite the innate toxicity challenge associated with SERCA inhibition, we identified CAD204520, a small molecule with better drug-like properties and reduced off-target Ca2+ toxicity compared with the SERCA inhibitor thapsigargin. In this work, we describe the properties and complex structure of CAD204520 and show that CAD204520 preferentially targets mutated over wild-type NOTCH1 proteins in T cell acute lymphoblastic leukemia (T-ALL) and mantle cell lymphoma (MCL). Uniquely among SERCA inhibitors, CAD204520 suppresses NOTCH1-mutated leukemic cells in a T-ALL xenografted model without causing cardiac toxicity. This study supports the development of SERCA inhibitors for Notch-dependent cancers and extends their application to cases with isolated mutations in the PEST degradation domain of NOTCH1, such as MCL or chronic lymphocytic leukemia (CLL). Clinical translation of SERCA inhibitors has been hampered by the risk of adverse cardiac events. In this work, Marchesini and Gherli et al. identified a tolerable oral available SERCA inhibitor, CAD204520, and showed that modulation of clinically relevant NOTCH1 mutations in T cell acute lymphoblastic leukemia and mantle cell lymphoma.",
keywords = "CAD204520, crystal structure, mantle cell lymphoma (MCL), NOTCH1, NOTCH1 mutation, P-type ATPases screening, PEST mutation, SERCA, T cell acute lymphoblastic leukemia (T-ALL), thapsigargin",
author = "Matteo Marchesini and Andrea Gherli and Anna Montanaro and Laura Patrizi and Claudia Sorrentino and Luca Pagliaro and Chiara Rompietti and Samuel Kitara and Sabine Heit and Olesen, {Claus E.} and M{\o}ller, {Jesper V.} and Monia Savi and Leonardo Bocchi and Rocchina Vilella and Federica Rizzi and Marilena Baglione and Giorgia Rastelli and Caterina Loiacono and {La Starza}, Roberta and Cristina Mecucci and Kimberly Stegmaier and Franco Aversa and Donatella Stilli and {Lund Winther}, {Anne Marie} and Paolo Sportoletti and Maike Bublitz and William Dalby-Brown and Giovanni Roti",
year = "2020",
month = jun,
doi = "10.1016/j.chembiol.2020.04.002",
language = "English",
volume = "27",
pages = "678--697.e13",
journal = "Cell Chemical Biology",
issn = "2451-9456",
publisher = "Elsevier Inc.",
number = "6",

}

RIS

TY - JOUR

T1 - Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia

AU - Marchesini, Matteo

AU - Gherli, Andrea

AU - Montanaro, Anna

AU - Patrizi, Laura

AU - Sorrentino, Claudia

AU - Pagliaro, Luca

AU - Rompietti, Chiara

AU - Kitara, Samuel

AU - Heit, Sabine

AU - Olesen, Claus E.

AU - Møller, Jesper V.

AU - Savi, Monia

AU - Bocchi, Leonardo

AU - Vilella, Rocchina

AU - Rizzi, Federica

AU - Baglione, Marilena

AU - Rastelli, Giorgia

AU - Loiacono, Caterina

AU - La Starza, Roberta

AU - Mecucci, Cristina

AU - Stegmaier, Kimberly

AU - Aversa, Franco

AU - Stilli, Donatella

AU - Lund Winther, Anne Marie

AU - Sportoletti, Paolo

AU - Bublitz, Maike

AU - Dalby-Brown, William

AU - Roti, Giovanni

PY - 2020/6

Y1 - 2020/6

N2 - The identification of SERCA (sarco/endoplasmic reticulum calcium ATPase) as a target for modulating gain-of-function NOTCH1 mutations in Notch-dependent cancers has spurred the development of this compound class for cancer therapeutics. Despite the innate toxicity challenge associated with SERCA inhibition, we identified CAD204520, a small molecule with better drug-like properties and reduced off-target Ca2+ toxicity compared with the SERCA inhibitor thapsigargin. In this work, we describe the properties and complex structure of CAD204520 and show that CAD204520 preferentially targets mutated over wild-type NOTCH1 proteins in T cell acute lymphoblastic leukemia (T-ALL) and mantle cell lymphoma (MCL). Uniquely among SERCA inhibitors, CAD204520 suppresses NOTCH1-mutated leukemic cells in a T-ALL xenografted model without causing cardiac toxicity. This study supports the development of SERCA inhibitors for Notch-dependent cancers and extends their application to cases with isolated mutations in the PEST degradation domain of NOTCH1, such as MCL or chronic lymphocytic leukemia (CLL). Clinical translation of SERCA inhibitors has been hampered by the risk of adverse cardiac events. In this work, Marchesini and Gherli et al. identified a tolerable oral available SERCA inhibitor, CAD204520, and showed that modulation of clinically relevant NOTCH1 mutations in T cell acute lymphoblastic leukemia and mantle cell lymphoma.

AB - The identification of SERCA (sarco/endoplasmic reticulum calcium ATPase) as a target for modulating gain-of-function NOTCH1 mutations in Notch-dependent cancers has spurred the development of this compound class for cancer therapeutics. Despite the innate toxicity challenge associated with SERCA inhibition, we identified CAD204520, a small molecule with better drug-like properties and reduced off-target Ca2+ toxicity compared with the SERCA inhibitor thapsigargin. In this work, we describe the properties and complex structure of CAD204520 and show that CAD204520 preferentially targets mutated over wild-type NOTCH1 proteins in T cell acute lymphoblastic leukemia (T-ALL) and mantle cell lymphoma (MCL). Uniquely among SERCA inhibitors, CAD204520 suppresses NOTCH1-mutated leukemic cells in a T-ALL xenografted model without causing cardiac toxicity. This study supports the development of SERCA inhibitors for Notch-dependent cancers and extends their application to cases with isolated mutations in the PEST degradation domain of NOTCH1, such as MCL or chronic lymphocytic leukemia (CLL). Clinical translation of SERCA inhibitors has been hampered by the risk of adverse cardiac events. In this work, Marchesini and Gherli et al. identified a tolerable oral available SERCA inhibitor, CAD204520, and showed that modulation of clinically relevant NOTCH1 mutations in T cell acute lymphoblastic leukemia and mantle cell lymphoma.

KW - CAD204520

KW - crystal structure

KW - mantle cell lymphoma (MCL)

KW - NOTCH1

KW - NOTCH1 mutation

KW - P-type ATPases screening

KW - PEST mutation

KW - SERCA

KW - T cell acute lymphoblastic leukemia (T-ALL)

KW - thapsigargin

UR - http://www.scopus.com/inward/record.url?scp=85086360678&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2020.04.002

DO - 10.1016/j.chembiol.2020.04.002

M3 - Journal article

C2 - 32386594

AN - SCOPUS:85086360678

VL - 27

SP - 678-697.e13

JO - Cell Chemical Biology

JF - Cell Chemical Biology

SN - 2451-9456

IS - 6

ER -