| Identification | Back Directory | [Name]
N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide | [CAS]
702675-74-9 | [Synonyms]
BX 795
CS-544
BX795, >97%
BX795/BX-795
BX 795, >=98%
BX-795 hydrochloride
BX-795; BX 795; BX795.
BX-795 - CAS 702675-74-9 - Calbiochem
N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrr
N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)aMino]propyl]aMino]-2-pyriMidinyl]aMino]phenyl]-1-pyrrolidin
N-(3-(5-IODO-4-(3-(THIOPHENE-2-CARBOXAMIDO)PROPYLAMINO)PYRIMIDIN-2-YLAMINO)PHENYL)PYRROLIDINE-1-CARBOXAMIDE
N-{3-[(5-iodo-4-{[3-(thiophen-2-ylformamido)propyl]amino}pyrimidin-2-yl)amino]phenyl}pyrrolidine-1-carboxamide
N-[3-[[5-iodo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide
N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide
1-Pyrrolidinecarboxamide,N-[3-[[5-iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-
BX795N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide
N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide USP/EP/BP
N-[3-[[5-iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-Pyrrolidinecarboxamide hydrochloride
N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide BX-795 | [EINECS(EC#)]
200-256-5 | [Molecular Formula]
C23H26IN7O2S | [MDL Number]
MFCD26406408 | [MOL File]
702675-74-9.mol | [Molecular Weight]
591.471 |
| Chemical Properties | Back Directory | [Melting point ]
>163°C (dec.) | [density ]
1.644 | [storage temp. ]
2-8°C | [solubility ]
DMSO: soluble15mg/mL, clear | [form ]
powder | [pka]
12.57±0.70(Predicted) | [color ]
white to light brown | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | [InChIKey]
VAVXGGRQQJZYBL-UHFFFAOYSA-N |
| Hazard Information | Back Directory | [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.1 BX-795 is a potent, ATP-competitive inhibitor of PDK1 in vitro (IC50 = 11 nM) and in cells (IC50 = 300 nM).2 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.3,4,5 | [Uses]
BX795 was initially developed as a PDK1 inhibitor (direct competitive inhibitor IC50 = 11nM for PDK1) and has been shown to be a potent and relatively specific inhibitor of TBK1 and IKK-ε. It blocks the phosphorylation, nuclear translocation, and transcriptional activity of interferon regulatory factor 3. BX795 also is a potent inhibitor of cell growth of multiple cancer cell lines with IC50 values ranging from submicromolar amounts (0.368 μM to greater than 450 μM). | [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). | [Enzyme inhibitor]
This nonselective signal transduction inhibitor and antineoplastic agent (FW
= 591.47 g/mol; CAS 702675-74-9; Solubility: 120 mg/mL DMSO; <1
mg/mL Water), systematically named N- (3- (5-iodo-4- (3- (thiophene-2-
carboxamido) propylamino) pyrimidin-2-ylamino) phenyl) pyrrolidine-1-
carboxamide, targets the phosphoinositide 3-kinase/3-phosphoinositide-
dependent kinase 1 (PDK1) /Akt signaling pathway plays a key role in
cancer cell growth, survival, and tumor angiogenesis and represents a
promising target for anticancer drugs. BX-795 targets TBK1 (IC50 = 6 nM),
IKKε (IC50 = 41 nM), PDK-1 (IC50 = 111 nM), and ERK8 (IC50 = 140 nM),
but acts more broadly by inhibiting MARK1 (IC50 = 55 nM), MARK2 (IC50
= 53 nM), MARK4 (IC50 = 19 nM), NUAK1 (IC50 = 5 nM), VEGFR (IC50 =
157 nM), MLK1 (IC50 = 50 nM), MLK2 (IC50 = 46 nM), MLK3 (IC50 = 42
nM). BX795 also inhibits the phosphorylation of JNK1/2 and p38α MAPK
in MEFs stimulated with IL-1α or TNFα. The effect of BX795 on the
activation of JNK1/2 and p38α MAPK does not result from the inhibition of TBK1/IKKε. | [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 |
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