Synonym
BX-517; BX 517; BX517; PDK1 inhibitor2.
IUPAC/Chemical Name
(Z)-N-(3-(1-(1H-pyrrol-2-yl)ethylidene)-2-hydroxy-3H-indol-5-yl)carbamimidic acid
InChi Key
DFURSNCTQGJRRX-JYRVWZFOSA-N
InChi Code
InChI=1S/C15H14N4O2/c1-8(11-3-2-6-17-11)13-10-7-9(18-15(16)21)4-5-12(10)19-14(13)20/h2-7,17H,1H3,(H,19,20)(H3,16,18,21)/b13-8-
SMILES Code
OC(NC1=CC2=C(N=C(O)/C2=C(C3=CC=CN3)/C)C=C1)=N
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
BX517 is an inhibitor of PDK1 with IC50 of 6 nM.
In vitro activity:
Based on potency and ease of synthesis 4i (BX517) was selected for further evaluation (Table 5). 4i had similar activity in the PDK1 assay and in the PDK1 mediated AKT2 activation assay (cAKT2) supporting that these indolinone inhibitors blocked Akt activity by inhibiting PDK1. Additionally, 4i blocked AKT2 activation in cells with submicromolar potency. The PKA selectivity was 320-fold, exceeding the goal of the project. Because of the close homology of PKA with PDK1, we hypothesized that a compound with high selectivity against PKA would also have high selectivity against other kinases. This was borne out by further profiling. 4i was 100-fold selective or better against a panel of seven additional Ser/Thr and Tyr kinases.
Reference: Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8. https://pubmed.ncbi.nlm.nih.gov/17531483/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
41.5 |
147.01 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
282.30
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Islam I, Bryant J, Chou YL, Kochanny MJ, Lee W, Phillips GB, Yu H, Adler M, Whitlow M, Ho E, Lentz D, Polokoff MA, Subramanyam B, Wu JM, Zhu D, Feldman RI, Arnaiz DO. Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8. doi: 10.1016/j.bmcl.2007.04.071. Epub 2007 Apr 27. PMID: 17531483.
In vitro protocol:
1. Islam I, Bryant J, Chou YL, Kochanny MJ, Lee W, Phillips GB, Yu H, Adler M, Whitlow M, Ho E, Lentz D, Polokoff MA, Subramanyam B, Wu JM, Zhu D, Feldman RI, Arnaiz DO. Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8. doi: 10.1016/j.bmcl.2007.04.071. Epub 2007 Apr 27. PMID: 17531483.
1: Islam I, Brown G, Bryant J, Hrvatin P, Kochanny MJ, Phillips GB, Yuan S, Adler M, Whitlow M, Lentz D, Polokoff MA, Wu J, Shen J, Walters J, Ho E, Subramanyam B, Zhu D, Feldman RI, Arnaiz DO. Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3819-25. PubMed PMID: 17544272.
2: Islam I, Bryant J, Chou YL, Kochanny MJ, Lee W, Phillips GB, Yu H, Adler M, Whitlow M, Ho E, Lentz D, Polokoff MA, Subramanyam B, Wu JM, Zhu D, Feldman RI, Arnaiz DO. Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8. PubMed PMID: 17531483.
