Synonym
PS210; PS-210; PS 210;
IUPAC/Chemical Name
2-(3-Oxo-1-phenyl-3-(4-(trifluoromethyl)phenyl)propyl)malonic acid
InChi Key
MLJPLHGJBUWCBA-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H15F3O5/c20-19(21,22)13-8-6-12(7-9-13)15(23)10-14(11-4-2-1-3-5-11)16(17(24)25)18(26)27/h1-9,14,16H,10H2,(H,24,25)(H,26,27)
SMILES Code
O=C(O)C(C(C1=CC=CC=C1)CC(C2=CC=C(C(F)(F)F)C=C2)=O)C(O)=O
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:
PS210 is a substrate-selective inhibitor of protein kinase PDK1.
In vitro activity:
The PIF-pocket of AGC protein kinases participates in the physiologic mechanism of regulation by acting as a docking site for substrates and as a switch for the transduction of the conformational changes needed for activation or inhibition. We describe the effects of compounds that bind to the PIF-pocket of PDK1. In vitro, PS210 is a potent activator of PDK1, and the crystal structure of the PDK1-ATP-PS210 complex shows that PS210 stimulates the closure of the kinase domain. However, in cells, the prodrug of PS210 (PS423) acts as a substrate-selective inhibitor of PDK1, inhibiting the phosphorylation and activation of S6K, which requires docking to the PIF-pocket, but not affecting PKB/Akt. This work describes a tool to study the dynamics of PDK1 activity and a potential approach for drug discovery.
Reference: Busschots K, Lopez-Garcia LA, Lammi C, Stroba A, Zeuzem S, Piiper A, Alzari PM, Neimanis S, Arencibia JM, Engel M, Schulze JO, Biondi RM. Substrate-selective inhibition of protein kinase PDK1 by small compounds that bind to the PIF-pocket allosteric docking site. Chem Biol. 2012 Sep 21;19(9):1152-63. doi: 10.1016/j.chembiol.2012.07.017. PMID: 22999883.
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
262.94 |
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
380.31
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:
Busschots K, Lopez-Garcia LA, Lammi C, Stroba A, Zeuzem S, Piiper A, Alzari PM, Neimanis S, Arencibia JM, Engel M, Schulze JO, Biondi RM. Substrate-selective inhibition of protein kinase PDK1 by small compounds that bind to the PIF-pocket allosteric docking site. Chem Biol. 2012 Sep 21;19(9):1152-63. doi: 10.1016/j.chembiol.2012.07.017. PMID: 22999883.
In vitro protocol:
Busschots K, Lopez-Garcia LA, Lammi C, Stroba A, Zeuzem S, Piiper A, Alzari PM, Neimanis S, Arencibia JM, Engel M, Schulze JO, Biondi RM. Substrate-selective inhibition of protein kinase PDK1 by small compounds that bind to the PIF-pocket allosteric docking site. Chem Biol. 2012 Sep 21;19(9):1152-63. doi: 10.1016/j.chembiol.2012.07.017. PMID: 22999883.
1: Hu J, Sun XM, Su JY, Zhao YF, Chen YX. Different phosphorylation and farnesylation patterns tune Rnd3-14-3-3 interaction in distinct mechanisms. Chem Sci. 2021 Jan 26;12(12):4432-4442. doi: 10.1039/d0sc05838f. PMID: 34163708; PMCID: PMC8179448.
2: Liu W, Li P, Mei Y. Discovery of SBF1 as an allosteric inhibitor targeting the PIF-pocket of 3-phosphoinositide-dependent protein kinase-1. J Mol Model. 2019 Jun 13;25(7):187. doi: 10.1007/s00894-019-4069-5. PMID: 31197600.
3: Paunović A, Milisavljević F, Bošković J. Evaluation of clinical characteristics as indicators for shunt procedure in patients with medulloblastoma: PS210. Porto Biomed J. 2017 Sep-Oct;2(5):240-241. doi: 10.1016/j.pbj.2017.07.151. Epub 2017 Sep 1. PMID: 32258762; PMCID: PMC6806795.
4: Schelhorn C, Martín-Malpartida P, Suñol D, Macias MJ. Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation. Sci Rep. 2015 Oct 12;5:14990. doi: 10.1038/srep14990. PMID: 26456073; PMCID: PMC4601027.
5: Busschots K, Lopez-Garcia LA, Lammi C, Stroba A, Zeuzem S, Piiper A, Alzari PM, Neimanis S, Arencibia JM, Engel M, Schulze JO, Biondi RM. Substrate- selective inhibition of protein kinase PDK1 by small compounds that bind to the PIF-pocket allosteric docking site. Chem Biol. 2012 Sep 21;19(9):1152-63. doi: 10.1016/j.chembiol.2012.07.017. PMID: 22999883.
6: Tomizawa K, Omori A, Ohtake A, Sato K, Takahashi M. Tau-tubulin kinase phosphorylates tau at Ser-208 and Ser-210, sites found in paired helical filament-tau. FEBS Lett. 2001 Mar 16;492(3):221-7. doi: 10.1016/s0014-5793(01)02256-6. PMID: 11257498.
