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

[1] RICHARD I FELDMAN. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1.[J]. The Journal of Biological Chemistry, 2005, 280 20: 19867-19874. DOI:10.1074/jbc.m501367200
[2] JENNY BAIN. The selectivity of protein kinase inhibitors: a further update.[J]. Biochemical Journal, 2007: 297-315. DOI:10.1042/bj20070797
[3] KRISTOPHER CLARK. Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation.[J]. The Journal of Biological Chemistry, 2009, 284 21: 14136-14146. DOI:10.1074/jbc.m109.000414
[4] LI-YUAN BAI . BX795, a TBK1 inhibitor, exhibits antitumor activity in human oral squamous cell carcinoma through apoptosis induction and mitotic phase arrest[J]. European journal of pharmacology, 2015, 769: Pages 287-296. DOI:10.1016/j.ejphar.2015.11.032
[5] EUN A CHOI . A pharmacogenomic analysis using L1000CDS2 identifies BX-795 as a potential anticancer drug for primary pancreatic ductal adenocarcinoma cells[J]. Cancer letters, 2019, 465: Pages 82-93. DOI:10.1016/j.canlet.2019.08.002
[6] SARAH A SCUDERI. TBK1 Inhibitor Exerts Antiproliferative Effect on Glioblastoma Multiforme Cells.[J]. Oncology Research, 2021, 28 7: 779-790. DOI:10.3727/096504021x16161478258040
[7] TOLGA SUTLU. Inhibition of intracellular antiviral defense mechanisms augments lentiviral transduction of human natural killer cells: implications for gene therapy.[J]. Human gene therapy, 2012, 23 10: 1090-1100. DOI:10.1089/hum.2012.080
[8] DAVID S J ALLAN. Systematic improvements in lentiviral transduction of primary human natural killer cells undergoing ex vivo expansion.[J]. Molecular Therapy. Methods & Clinical Development, 2021: 559-571. DOI:10.1016/j.omtm.2021.01.008
[9] PETER CHOCKLEY  Stephen G  Sagar L Patil. Transient blockade of TBK1/IKKε allows efficient transduction of primary human natural killer cells with vesicular stomatitis virus G-pseudotyped lentiviral vectors[J]. Cytotherapy, 2021, 23 9: Pages 787-792. DOI:10.1016/j.jcyt.2021.04.010
[10] LINGYU LI. Lentiviral delivery of combinatorial CAR/CRISPRi circuit into human primary T cells is enhanced by TBK1/IKKɛ complex inhibitor BX795.[J]. Journal of Translational Medicine, 2020: 363. DOI:10.1186/s12967-020-02526-2