K03861CDK2 inhibitor CAS# 853299-07-7 |
- SB 431542
Catalog No.:BCC3658
CAS No.:301836-41-9
- SB-505124 hydrochloride
Catalog No.:BCC1930
CAS No.:356559-13-2
- SB525334
Catalog No.:BCC2531
CAS No.:356559-20-1
- A 77-01
Catalog No.:BCC1318
CAS No.:607737-87-1
- LY2109761
Catalog No.:BCC3806
CAS No.:700874-71-1
- LY2157299
Catalog No.:BCC3709
CAS No.:700874-72-2
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 853299-07-7 | SDF | Download SDF |
PubChem ID | 11260561 | Appearance | Powder |
Formula | C24H26F3N7O2 | M.Wt | 501.5 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | >50.2mg/mL in DMSO | ||
Chemical Name | 1-[4-(2-aminopyrimidin-4-yl)oxyphenyl]-3-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea | ||
SMILES | CN1CCN(CC1)CC2=C(C=C(C=C2)NC(=O)NC3=CC=C(C=C3)OC4=NC(=NC=C4)N)C(F)(F)F | ||
Standard InChIKey | PWDLXPJQFNVTNL-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C24H26F3N7O2/c1-33-10-12-34(13-11-33)15-16-2-3-18(14-20(16)24(25,26)27)31-23(35)30-17-4-6-19(7-5-17)36-21-8-9-29-22(28)32-21/h2-9,14H,10-13,15H2,1H3,(H2,28,29,32)(H2,30,31,35) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | K03861 is a type II CDK2 inhibitor with Kd of 8.2 nM.
K03861 inhibits CDK2 activity by competing with binding of activating cyclins. References: |
K03861 Dilution Calculator
K03861 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 1.994 mL | 9.9701 mL | 19.9402 mL | 39.8804 mL | 49.8504 mL |
5 mM | 0.3988 mL | 1.994 mL | 3.988 mL | 7.9761 mL | 9.9701 mL |
10 mM | 0.1994 mL | 0.997 mL | 1.994 mL | 3.988 mL | 4.985 mL |
50 mM | 0.0399 mL | 0.1994 mL | 0.3988 mL | 0.7976 mL | 0.997 mL |
100 mM | 0.0199 mL | 0.0997 mL | 0.1994 mL | 0.3988 mL | 0.4985 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
K03861 is a type II inhibitor of CDK2. The cyclin-dependent kinase holoenzymes contain a catalytic subunit, the Cdk, a family of regulatory subunits, and the cyclins. Cdks are the catalytic subunits of the mammalian heterodimeric serine/threonine kinases progression, Cyclin-dependent kinases (CDKs) play important roles in the cell cycle regulation, transcription, and neuronal function. CDKs are frequently deregulated in some human tumours. The inhibitors targeted CDK are thought to prevent cell proliferation regulating cyclin-CDK complexes. The central role of CDKs in cell cycle regulation makes them a promising target for studying inhibitory molecules that can modify the cell proliferation [1].
K03861 is an aminopyrimidine-phenyl urea inhibitor of CDK2. The type II inhibitor CDK2 cocrystal structure of CDK2 with the inhibitor K03861 revealed a canonical type II binding mode. The type II inhibitors could compete with the binding of cyclins. The residues important for the type II inhibitors may be distant to the ATP binding pockets. The crystal structure of this complex may provide a foundation for the cyclin-competitive CDK2 inhibitors [2].
References:
Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases[J]. Trends in biochemical sciences, 2005, 30(11): 630-641.
Alexander L T, Mo?bitz H, Drueckes P, et al. Type II inhibitors targeting CDK2[J]. ACS chemical biology, 2015, 10(9): 2116-2125.
- Trichorabdal A
Catalog No.:BCN4404
CAS No.:85329-59-5
- Hythiemoside A
Catalog No.:BCN4403
CAS No.:853267-91-1
- Ajugalide D
Catalog No.:BCN3665
CAS No.:853247-65-1
- Ajugalide C
Catalog No.:BCN8015
CAS No.:853247-64-0
- PG 01
Catalog No.:BCC7820
CAS No.:853138-65-5
- Anthraquinone-1,5-disulfonic acid disodium salt
Catalog No.:BCC8833
CAS No.:853-35-0
- Dehydroepiandrosterone acetate
Catalog No.:BCC8929
CAS No.:853-23-6
- 20(21)-Dehydrolucidenic acid A
Catalog No.:BCN2940
CAS No.:852936-69-7
- TCN 201
Catalog No.:BCC6122
CAS No.:852918-02-6
- 2,3-Dihydropodocarpusflavone A
Catalog No.:BCN6668
CAS No.:852875-96-8
- Sculponeatin A
Catalog No.:BCN4402
CAS No.:85287-60-1
- TP-808
Catalog No.:BCC6450
CAS No.:852821-06-8
- SecinH3
Catalog No.:BCC7503
CAS No.:853625-60-2
- 5,19-Epoxy-19S,25-dimethoxycucurbita-6,23-dien-3-ol
Catalog No.:BCN1329
CAS No.:85372-70-9
- 5,19-Epoxy-19R,25-dimethoxycucurbita-6,23-dien-3-ol
Catalog No.:BCN1328
CAS No.:85372-72-1
- SKF 89976A hydrochloride
Catalog No.:BCC6930
CAS No.:85375-15-1
- (+)-AJ 76 hydrochloride
Catalog No.:BCC6747
CAS No.:85378-82-1
- NVP-BAG956
Catalog No.:BCC1813
CAS No.:853910-02-8
- OGT 2115
Catalog No.:BCC7458
CAS No.:853929-59-6
- Dasatinib hydrochloride
Catalog No.:BCC1517
CAS No.:854001-07-3
- Norcaesalpinin E
Catalog No.:BCN7006
CAS No.:854038-96-3
- (-)-Haplomyrfolin
Catalog No.:BCN3225
CAS No.:85404-48-4
- Ropivacaine mesylate
Catalog No.:BCC9137
CAS No.:854056-07-8
- Rilmenidine Phosphate
Catalog No.:BCC5637
CAS No.:85409-38-7
Type II Inhibitors Targeting CDK2.[Pubmed:26158339]
ACS Chem Biol. 2015 Sep 18;10(9):2116-25.
Kinases can switch between active and inactive conformations of the ATP/Mg(2+) binding motif DFG, which has been explored for the development of type I or type II inhibitors. However, factors modulating DFG conformations remain poorly understood. We chose CDK2 as a model system to study the DFG in-out transition on a target that was thought to have an inaccessible DFG-out conformation. We used site-directed mutagenesis of key residues identified in structural comparisons in conjunction with biochemical and biophysical characterization of the generated mutants. As a result, we identified key residues that facilitate the DFG-out movement, facilitating binding of type II inhibitors. However, surprisingly, we also found that wild type CDK2 is able to bind type II inhibitors. Using protein crystallography structural analysis of the CDK2 complex with an aminopyrimidine-phenyl urea inhibitor (K03861) revealed a canonical type II binding mode and the first available type II inhibitor CDK2 cocrystal structure. We found that the identified type II inhibitors compete with binding of activating cyclins. In addition, analysis of the binding kinetics of the identified inhibitors revealed slow off-rates. The study highlights the importance of residues that may be distant to the ATP binding pocket in modulating the energetics of the DFG-out transition and hence inhibitor binding. The presented data also provide the foundation for a new class of slow off-rate cyclin-competitive CDK2 inhibitors targeting the inactive DFG-out state of this important kinase target.