![N-[3-[[5-Iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide structure, CAS 702675-74-9](/structures/60000/57957_1_702675_74_9.png)
| Chemical & Physical Properties | |
|---|---|
| CAS Number | 702675-74-9 |
| Catalog No. | 2A-9057957 |
| Chinese Name | BX 795 |
| Synonyms | cc-617; BX 795; BX795; BX-795 |
| Molecular Formula | C23H26IN7O2S |
| Molecular Weight | 591.47 |
| Purity | ≥95 (HPLC) |
| Density | 1.6±0.1 g/cm3 |
| Appearance | solid |
| Water Solubility | DMSO: soluble15mg/mL, clear |
| Storage Condition | 2-8°C |
| Application | BX795 is a potent and selective PDK1 inhibitor with an IC50 of 6 nM, which is more than 50 times more selective than PKA, PKC, c-Kit, and GSK3β. |
| MDL Number | MFCD12546134 |
| SMILES | Ic1c(nc(nc1)Nc3cc(ccc3)NC(=O)N4CCCC4)NCCCNC(=O)c2[s]ccc2 |
| InChI | 1S/C23H26IN7O2S/c24-18-15-27-22(30-20(18)25-9-5-10-26-21(32)19-8-4-13-34-19)28-16-6-3-7-17(14-16)29-23(33)31-11-1-2-12-31/h3-4,6-8,13-15H,1-2,5,9-12H2,(H,26,32)(H,29,33)(H2,25,27,28,30) |
| InChI Key | VAVXGGRQQJZYBL-UHFFFAOYSA-N |
| NACRES Code | NA.77 |
| UNSPSC | 12352200 |
| Hazard Symbols | transportation |
| MSDS | msds/57957_1_702675_74_9.pdf |
| Bioactivity | BX795 is a potent and selective PDK1 inhibitor with an IC50 of 6 nM, showing 50-fold selectivity over PKA, PKC, c-Kit, GSK3β etc. Related Catalog Signaling Pathways >> PI3K/Akt/mTOR >> PDK-1 Research Areas >> Cancer Target IC50: 2 nM (TBK1), 6 nM (PDK1) In Vitro BX795 effectively blocks PDK1 activity in PC-3 cells, as shown by their ability to block phosphorylation of S6K1, Akt, PKCδ, and GSK3β. BX795 potently inhibits tumor cell growth on plastic with IC50 of 1.6, 1.4, and 1.9 μM for MDA-468, HCT-116 and MiaPaca cells, respectively. In soft agar, BX795 displays higher growth inhibition with IC50 of 0.72, and 0.25 μM for MDA-468, and PC-3 cells, respectively[1]. In addition, BX795, as an inhibitor of the TBK1/IKKε, blocks TBK1- and IKKε-mediated activation of IRF3 and production of IFN-β[2]. In platelet physiological responses, BX795 produces inhibitory effect on 2-MeSADP-induced or collagen-induced aggregation, ATP secretion and thromboxane generation[3]. Kinase Assay PDK1 is assayed in a direct kinase assay and a coupled assay format measuring PDK1- and PtdIns-3,4-P2-mediated activation of AKT2. For the coupled assay, the final assay mixture (60 μL) contained: 15 mM MOPS, pH 7.2, 1 mg/mL bovine serum albumin, 18 mM β-glycerol phosphate, 0.7 mM dithiothreitol, 3 mM EGTA, 10 mM MgOAc, 7.5 μM ATP, 0.2 μCi of [γ-33P]ATP, 7.5 μM biotinylated peptide substrate (biotin-ARRRDGGGAQPFRPRAATF), 0.5 μL of PtdIns-3,4-P2-containing phospholipid vesicles, 60 pg of purified recombinant human PDK1, and 172 ng of purified recombinant human AKT2. After incubation for 2 h at room temperature, the biotin-labeled peptide is captured from 10 μL of the assay mixture on streptavidin-coated SPA beads, and product formation is measured by scintillation proximity in a Wallac MicroBeta counter. The product formed is proportional to the time of incubation and to the amount of PDK1 and inactive AKT2 added. PDK1 is added at suboptimal levels so that the assay could sensitively detect inhibitors of AKT2 activation as well as direct inhibitors of PDK1 or AKT2. To measure PDK1 activity directly, the final assay mixture (60 μL) contained 50 mM Tris-HCl, pH 7.5, 0.1 mM EGTA, 0.1 mM EDTA, 0.1% β-mercaptoethanol, 1 mg/mL bovine serum albumin, 10 mM MgOAc, 10 μM ATP, 0.2 μCi of [γ-33P]ATP, 7.5 μM substrate peptide (H2N-ARRRGVTTKTFCGT), and 60 ng of purified recombinant human PDK1. After 4 h at room temperature, we add 25 mM EDTA and spotted a portion of the reaction mixture on Whatman P81 phosphocellulose paper. The filter paper is washed three times with 0.75% phosphoric acid and once with acetone. After drying, the filter-bound labeled peptide is quantified using a Fuji phosphorimager. Cell Assay Cells seeded at a low density (1,500-3,000 cells/well, 0.1 mL/well, 96-well plates) are incubated overnight. Compound treatments are made by adding 10 μL/well of the compound in 1% dimethyl sulfoxide and growth medium (final concentration of dimethyl sulfoxide, 0.1%), followed by brief shaking. Treated cells are incubated for 72 hours, and viability is measured by the addition of 10 μL of the metabolic dye WST-1. The WST-1 signal is read in a plate reader at 450 nm, and a no cell, or zero time cell, background is subtracted to calculate the net signal. Results are reported as the average±S.E. of two or more replicates. References [1]. Feldman RI, et al. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74. [2]. Clark K, et al. 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 Biol Chem. 2009 May 22;284(21):141 [3]. Dangelmaier C, et al. PDK1 selectively phosphorylates Thr(308) on Akt and contributes to human platelet functional responses. Thromb Haemost. 2014 Mar 3;111(3):508-17. Chemical & Physical Properties Density 1.6±0.1 g/cm3 Molecular Formula C23H26IN7O2S Molecular Weight 591.468 Exact Mass 591.091309 PSA 139.52000 LogP 2.73 Appearance of Characters white to light brown Index of Refraction 1.738 InChIKey VAVXGGRQQJZYBL-UHFFFAOYSA-N SMILES O=C(NCCCNc1nc(Nc2cccc(NC(=O)N3CCCC3)c2)ncc1I)c1cccs1 Storage condition 2-8°C Water Solubility DMSO: soluble15mg/mL, clear |
| Use of | BX795 is a potent and selective PDK1 inhibitor with an IC50 of 6 nM, showing 50-fold selectivity over PKA, PKC, c-Kit, GSK3β etc. Properties Name N-[3-[[5-iodo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide Synonym More Synonyms BX-795 Biological Activity Description BX795 is a potent and selective PDK1 inhibitor with an IC50 of 6 nM, showing 50-fold selectivity over PKA, PKC, c-Kit, GSK3β etc. Related Catalog Signaling Pathways >> PI3K/Akt/mTOR >> PDK-1 Research Areas >> Cancer IC50: 2 nM (TBK1), 6 nM (PDK1) References [1]. Feldman RI, et al. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74. [2]. Clark K, et al. 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 Biol Chem. 2009 May 22;284(21):141 [3]. Dangelmaier C, et al. PDK1 selectively phosphorylates Thr(308) on Akt and contributes to human platelet functional responses. Thromb Haemost. 2014 Mar 3;111(3):508-17. Chemical & Physical Properties Molecular Formula C23H26IN7O2S Exact Mass 591.091309 PSA 139.52000 Appearance of Characters white to light brown Index of Refraction 1.738 InChIKey VAVXGGRQQJZYBL-UHFFFAOYSA-N |
| Transport Info | Shipping Name: UN |
| MSDS Transport Info | Module 14. Shipping information European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.2 United Nations shipping name European Land Transport Dangerous Regulations: Non-dangerous goods IMDG Code: Non-dangerous goods International air transport dangerous goods regulations: non-dangerous goods 14.3 Transport hazard categories European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.4 Package group European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.5 Environmental hazards European Land Transport Danger Regulations: No International Maritime Danger Regulations International Air Transport Danger Regulations: No Marine pollutants (yes/no): No 14.6 Special reminder to users No data available |
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