N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide

Description

3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine-threonine kinase that phosphorylates and activates a range of other kinases, including PKB, PKA, and certain isoforms of PKC. BX-795 is a potent, ATP-competitive inhibitor of PDK1 in vitro (IC₅₀ = 11 nM) and in cells (IC₅₀ = 300 nM). At comparable concentrations, BX-795 also inhibits ERK8, MAPK-interacting kinase 2, Aurora B, Aurora C, MAP/microtubule affinity-regulating kinases 1-4, TNF receptor associated factor-associated NF-κB activator-binding kinase 1, IκB kinase ε, and additional kinases.

Uses

BX-795 hydrochloride has been used to study the effect of kinase inhibition on human endogenous retroviruses (HERVs) transcription activation.

Definition

ChEBI: N-[3-[[5-iodo-4-[3-[[oxo(thiophen-2-yl)methyl]amino]propylamino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide is a member of ureas.

Biochem/physiol Actions

BX-795 competes for the ATP (adenosine triphosphate) binding pocket of 3-phosphoinositide-dependent kinase-1 (PDK1) with its substrate ATP. In vitro assays reveal that BX-795 might inhibit Unc-51 (serine/threonine-protein kinase)-like autophagy activating kinase (ULK1).

storage

Store at -20°C

References

Feldman et al. (2005) Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1; J. Biol. Chem.?280 19867 Bain et al. (2007) The selectivity of protein kinase inhibitors: a further update; Biochem.? J. 408 297 Clark et al. (2009) Use of the Pharmacological Inhibitor BX795 to Study the Regulation and Physiological Roles of TBK1 and IkB Kinase ε; J.? Biol. Chem.?284 14136 Bai et al. (2015) BX795, a TBK1 inhibitor, exhibits antitumor activity in human oral squamous cell carcinoma through apoptosis induction and mitotic phase arrest; Eur.? J. Pharmacol.?769 287 Choi et al. (2019) A pharmacogenomic analysis using L1000CDS2 identifies BX-795 as a potential anticancer drug for primary pancreatic ductal adenocarcinoma cells; Cancer Lett.?465 82 Scuderi et al. (2021) TBK1 Inhibitor Exerts Antiproliferative Effect on Glioblastoma Multiforme Cells; Oncol.? Res.?28 779 Sutlu et al. (2012) Inhibition of Intracellular Antiviral Defense Mechanisms Augments Lentiviral Transduction of Human Natural Killer Cells: Implications for Gene Therapy; Hum. Gene Ther.?23 1090 Allan et al. (2021) Systematic improvements in lentiviral transduction of primary human natural killer cells undergoing e4x vivo expansion; Mol. Ther. Methods Clin. Dev.?20 559 Chockley et al. (2021) Transient blockade of TBK1/IKKε allows efficient transduction of primary human natural killer cells with vesicular stomatitis virus G-pseudotyped lentiviral vectors; Cytotherapy?23 787 Lingyu et al. (2020) Lentiviral delivery of combinatorial CAR/CRISPRi circuit into human primary T cells is enhanced by TBK1/IKKε complex inhibitor BX795; J. Transl. Med.?18 363