LY2857785CDK9 inhibitor CAS# 1619903-54-6 |
- BS-181
Catalog No.:BCC1439
CAS No.:1092443-52-1
- LEE011 succinate hydrate
Catalog No.:BCC4103
CAS No.:1374639-79-8
- AMG 925
Catalog No.:BCC5150
CAS No.:1401033-86-0
- Roscovitine (Seliciclib,CYC202)
Catalog No.:BCC1105
CAS No.:186692-46-6
- Palbociclib (PD0332991) Isethionate
Catalog No.:BCC3698
CAS No.:827022-33-3
- SB1317
Catalog No.:BCC1925
CAS No.:937270-47-8
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 1619903-54-6 | SDF | Download SDF |
PubChem ID | 78357764 | Appearance | Powder |
Formula | C26H36N6O | M.Wt | 448.6 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : 10 mg/mL (22.29 mM; Need ultrasonic) | ||
Chemical Name | 4-N-[4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]-1-N-(oxan-4-yl)cyclohexane-1,4-diamine | ||
SMILES | CC(C)C1=C2C=C(C=CC2=NN1C)C3=NC(=NC=C3)NC4CCC(CC4)NC5CCOCC5 | ||
Standard InChIKey | LHIUZPIDLZYPRL-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C26H36N6O/c1-17(2)25-22-16-18(4-9-24(22)31-32(25)3)23-10-13-27-26(30-23)29-20-7-5-19(6-8-20)28-21-11-14-33-15-12-21/h4,9-10,13,16-17,19-21,28H,5-8,11-12,14-15H2,1-3H3,(H,27,29,30) | ||
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 | LY2857785 is a type I reversible and competitive ATP kinase inhibitor against CDK9 (IC50 11 nM) and other transcription kinases CDK8 (IC50 16 nM), and CDK7 (IC50 246 nM).In Vitro:LY2857785 shows good selectivity against a panel of 114 protein kinases, with only 5 other protein kinases inhibited with potency (IC50) less than 0.1 μM, and a total of 14 kinases less than 1 μM. At the cellular level, LY2857785 inhibits CTD P-Ser2 and CTD P-Ser5 in U2OS cells at IC50s 0.089 (n=13) and 0.042 (n=1) μM, respectively. However, LY2857785 only induces a moderate G2-M DNA content increase, from 35% to 55%, with EC50 0.135 μM. LY2857785 shows potent compound exposure- and time-dependent cell proliferation inhibition in MV-4-11, RPMI8226, and L363 cells. When incubated between 4 to 24 hours, the cell growth inhibition potency reaches a maximal effect at 8 hours with IC50s 0.04, 0.2, and 0.5 μM for MV-4-11, RPMI8226, and L363 cells, respectively. LY2857785-induced cancer cell apoptosis is also time dependent, reaching maximal potency at 8 hours with IC50 0.5 μM in L363 cells[1].In Vivo:In HCT116 xenograft tumor-bearing mice, LY2857785 demonstrates dose-dependent RNAP II CTD P-Ser2 inhibition potently with TED50 of 4.4 mg/kg and TEC50 of 0.36 μM. LY2857785 also shows significant duration of CTD P-Ser2 inhibition for 3 to 6 hours at TED70 (8 mg/kg) in HCT116 and MV-4-11 nude mice xenograft models. In the nude rat MV-4-11 xenograft model, LY2857785 similarly shows dose-dependent CTD P-Ser2 inhibition for 8 hours at TED70 (7 mg/kg) and TED90 (10 mg/kg). LY2857785 demonstrates the most dramatic tumor regression in the AML MV-4-11 xenograft tumor model either by i.v. bolus in mice or i.v. infusion in rats[1]. References: |
LY2857785 Dilution Calculator
LY2857785 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.2292 mL | 11.1458 mL | 22.2916 mL | 44.5831 mL | 55.7289 mL |
5 mM | 0.4458 mL | 2.2292 mL | 4.4583 mL | 8.9166 mL | 11.1458 mL |
10 mM | 0.2229 mL | 1.1146 mL | 2.2292 mL | 4.4583 mL | 5.5729 mL |
50 mM | 0.0446 mL | 0.2229 mL | 0.4458 mL | 0.8917 mL | 1.1146 mL |
100 mM | 0.0223 mL | 0.1115 mL | 0.2229 mL | 0.4458 mL | 0.5573 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
LY2857785 was identified as a type I reversible and competitive ATP kinase inhibitor against CDK9 and other transcription kinases CDK8 and CDK7.[1,2]
Cdk7 acts as a Cdk-activating kinase and regulate transcription. Cdk8 and Cdk9 regulate transcription via phosphorylation of the RNA polymerase II carboxyl terminal domain. The Cdk9-related pathway performs an important role in several biological processes, such as cell growth, proliferation, protection from apoptosis and differentiation. These kinases are reported dys-regulation in some cancers. [2]
Transcription activation requires phosphorylation of a carboxyl-terminal domain, by a variety of kinases including CDK7, CDK8, and CDK9. By inhibiting these kinases, LY2857785 has unique transcription inhibitor activity. LY2857785 dramatically inhibited XIAP protein level in MV-4-11 and other hematologic cancer cells. It also can significantly reduce RNAP II CTD phosphorylation and dramatically decreases MCL1 protein levels to result in apoptosis in a variety of leukemia and solid tumor cell lines. [1]
LY2857785 potently inhibits a carboxyl-terminal domain phosphorylation and exhibits antitumor efficacy in orthotopic models of leukemia. LY2857785 inhibits the growth of leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia and chronic lymphocytic leukemia patient tumor samples. LY2857785 may be used in treating patients with hematologic tumors, particularly AML and CLL. [1]
References:
[1] Yin T, Lallena MJ, Kreklau EL etal. , A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models. Mol Cancer Ther. 2014 Jun;13(6):1442-56.
[2] Romano G1, Giordano A. Role of the cyclin-dependent kinase 9-related pathway in mammalian gene expression and human diseases. Cell Cycle. 2008 Dec;7(23):3664-8.
- Catechin pentaacetate
Catalog No.:BCN1718
CAS No.:16198-01-9
- Esomeprazole Magnesium
Catalog No.:BCC5007
CAS No.:161973-10-0
- Prehelminthosporol
Catalog No.:BCN7447
CAS No.:1619-13-2
- Segetalin A
Catalog No.:BCC9246
CAS No.:161875-97-4
- Talampanel(LY300164)
Catalog No.:BCC6378
CAS No.:161832-65-1
- Amprenavir (agenerase)
Catalog No.:BCC3619
CAS No.:161814-49-9
- Benzamil
Catalog No.:BCC7674
CAS No.:161804-20-2
- Ethyl 2-(3-cyano-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate
Catalog No.:BCC8966
CAS No.:161798-02-3
- Ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate
Catalog No.:BCC8968
CAS No.:161798-01-2
- Ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate
Catalog No.:BCC8969
CAS No.:161797-99-5
- Esomeprazole Sodium
Catalog No.:BCC4376
CAS No.:161796-78-7
- Palmatrubine
Catalog No.:BCN2647
CAS No.:16176-68-4
- GSK2801
Catalog No.:BCC6498
CAS No.:1619994-68-1
- Bromosporine
Catalog No.:BCC2226
CAS No.:1619994-69-2
- Rofecoxib
Catalog No.:BCC4437
CAS No.:162011-90-7
- UNC0379
Catalog No.:BCC8055
CAS No.:1620401-82-2
- L-371,257
Catalog No.:BCC7353
CAS No.:162042-44-6
- SC 58125
Catalog No.:BCC5948
CAS No.:162054-19-5
- Myriceric acid C
Catalog No.:BCN1719
CAS No.:162059-94-1
- Dimesna
Catalog No.:BCC1095
CAS No.:16208-51-8
- 4',4'''-Di-O-methylisochamaejasmin
Catalog No.:BCN6849
CAS No.:1620921-68-7
- SynaptoRedTM C2
Catalog No.:BCC8012
CAS No.:162112-35-8
- RWJ 50271
Catalog No.:BCC7894
CAS No.:162112-37-0
- Flunitrazepam
Catalog No.:BCC6107
CAS No.:1622-62-4
A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models.[Pubmed:24688048]
Mol Cancer Ther. 2014 Jun;13(6):1442-56.
DNA-dependent RNA polymerase II (RNAP II) largest subunit RPB1 C-terminal domain (CTD) kinases, including CDK9, are serine/threonine kinases known to regulate transcriptional initiation and elongation by phosphorylating Ser 2, 5, and 7 residues on CTD. Given the reported dysregulation of these kinases in some cancers, we asked whether inhibiting CDK9 may induce stress response and preferentially kill tumor cells. Herein, we describe a potent CDK9 inhibitor, LY2857785, that significantly reduces RNAP II CTD phosphorylation and dramatically decreases MCL1 protein levels to result in apoptosis in a variety of leukemia and solid tumor cell lines. This molecule inhibits the growth of a broad panel of cancer cell lines, and is particularly efficacious in leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia and chronic lymphocytic leukemia patient tumor samples. Thus, inhibition of CDK9 may represent an interesting approach as a cancer therapeutic target, especially in hematologic malignancies.