CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation

Sachin Mahale; Carine Aubry; A. James Wilson; Paul R. Jenkins; Jean Didier Maréchal; Michael J. Sutcliffe; Bhabatosh Chaudhuri

doi:10.1016/j.bmcl.2006.05.065

CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G₀/G₁ inhibiting pRB phosphorylation

Sachin Mahale, Carine Aubry, A. James Wilson, Paul R. Jenkins, Jean Didier Maréchal, Michael J. Sutcliffe, Bhabatosh Chaudhuri^*

^*Autor corresponent d’aquest treball

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Resum

Tryptamine derivatives, non-planar and potentially less toxic analogues of the anti-cancer agent fascaplysin, have been synthesised. They specifically inhibit Cdk4-D1 vis a vis Cdk2-A but, unlike fascaplysin, do not bind or intercalate DNA. CA224 is the most potent compound identified (Cdk4-D1 IC₅₀ ∼ 5.5 μM). As would be expected of a Cdk4 inhibitor that does not inhibit Cdk2, it maintains a G₀/G₁ block in synchronised cancer cells and inhibits Cdk4-specific phosphorylation of the retinoblastoma protein.

Idioma original	Anglès
Pàgines (de-a)	4272-4278
Nombre de pàgines	7
Revista	Bioorganic and Medicinal Chemistry Letters
Volum	16
Número	16
DOIs	https://doi.org/10.1016/j.bmcl.2006.05.065
Estat de la publicació	Publicada - 15 d’ag. 2006

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Accés al document

10.1016/j.bmcl.2006.05.065

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@article{6e2a8c5b6ae34102b88c3df91563daeb,

title = "CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation",

abstract = "Tryptamine derivatives, non-planar and potentially less toxic analogues of the anti-cancer agent fascaplysin, have been synthesised. They specifically inhibit Cdk4-D1 vis a vis Cdk2-A but, unlike fascaplysin, do not bind or intercalate DNA. CA224 is the most potent compound identified (Cdk4-D1 IC50 ∼ 5.5 μM). As would be expected of a Cdk4 inhibitor that does not inhibit Cdk2, it maintains a G0/G1 block in synchronised cancer cells and inhibits Cdk4-specific phosphorylation of the retinoblastoma protein.",

keywords = "Cell cycle, Cell growth inhibition, Cyclin-dependent kinases, DNA intercalation, G/G arrest, pRB",

author = "Sachin Mahale and Carine Aubry and \{James Wilson\}, A. and Jenkins, \{Paul R.\} and Mar{\'e}chal, \{Jean Didier\} and Sutcliffe, \{Michael J.\} and Bhabatosh Chaudhuri",

note = "Funding Information: The work in the authors{\textquoteright} laboratory was supported by Cancer Research, UK.",

year = "2006",

month = aug,

day = "15",

doi = "10.1016/j.bmcl.2006.05.065",

language = "English",

volume = "16",

pages = "4272--4278",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "16",

}

CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G₀/G₁ inhibiting pRB phosphorylation. / Mahale, Sachin; Aubry, Carine; James Wilson, A. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, Núm. 16, 15.08.2006, pàg. 4272-4278.

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

TY - JOUR

T1 - CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation

AU - Mahale, Sachin

AU - Aubry, Carine

AU - James Wilson, A.

AU - Jenkins, Paul R.

AU - Maréchal, Jean Didier

AU - Sutcliffe, Michael J.

AU - Chaudhuri, Bhabatosh

N1 - Funding Information: The work in the authors’ laboratory was supported by Cancer Research, UK.

PY - 2006/8/15

Y1 - 2006/8/15

N2 - Tryptamine derivatives, non-planar and potentially less toxic analogues of the anti-cancer agent fascaplysin, have been synthesised. They specifically inhibit Cdk4-D1 vis a vis Cdk2-A but, unlike fascaplysin, do not bind or intercalate DNA. CA224 is the most potent compound identified (Cdk4-D1 IC50 ∼ 5.5 μM). As would be expected of a Cdk4 inhibitor that does not inhibit Cdk2, it maintains a G0/G1 block in synchronised cancer cells and inhibits Cdk4-specific phosphorylation of the retinoblastoma protein.

AB - Tryptamine derivatives, non-planar and potentially less toxic analogues of the anti-cancer agent fascaplysin, have been synthesised. They specifically inhibit Cdk4-D1 vis a vis Cdk2-A but, unlike fascaplysin, do not bind or intercalate DNA. CA224 is the most potent compound identified (Cdk4-D1 IC50 ∼ 5.5 μM). As would be expected of a Cdk4 inhibitor that does not inhibit Cdk2, it maintains a G0/G1 block in synchronised cancer cells and inhibits Cdk4-specific phosphorylation of the retinoblastoma protein.

KW - Cell cycle

KW - Cell growth inhibition

KW - Cyclin-dependent kinases

KW - DNA intercalation

KW - G/G arrest

KW - pRB

UR - https://www.scopus.com/pages/publications/33745727153

U2 - 10.1016/j.bmcl.2006.05.065

DO - 10.1016/j.bmcl.2006.05.065

M3 - Article

AN - SCOPUS:33745727153

SN - 0960-894X

VL - 16

SP - 4272

EP - 4278

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -