Synonym
LY2857785; LY-2857785; LY 2857785.
IUPAC/Chemical Name
(1r,4r)-N1-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-N4-(tetrahydro-2H-pyran-4-yl)cyclohexane-1,4-diamine
InChi Key
LHIUZPIDLZYPRL-MXVIHJGJSA-N
InChi Code
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)/t19-,20-
SMILES Code
CN1C(C(C)C)=C(C(C=C2)=N1)C=C2C3=NC(N[C@H]4CC[C@H](NC5CCOCC5)CC4)=NC=C3
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, not in water
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:
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 activity:
Herein, this study describes 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.
Mol Cancer Ther. 2014 Jun;13(6):1442-56. https://pubmed.ncbi.nlm.nih.gov/24688048/
In vivo activity:
LY2857785 treatment, as well as Cdk9 knock-down, led to lowered expression of Bmal1 in accordance with elevated expression of Rev-Erbα. To conform the circadian-modulating activity of CDK9 in vivo, this study knocked down CDK9 in mice at the anterior hypothalamus covering the central oscillator SCN, and found the respiratory exchange ratio, daily activity and circadian period were altered in the Cdk9-knockdown mice.
Reference: Biochem Biophys Res Commun. 2019 Jun 11;513(4):967-973. https://pubmed.ncbi.nlm.nih.gov/31005255/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
16.5 |
36.78 |
| Ethanol |
42.0 |
93.62 |
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
448.62
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. Yin T, Lallena MJ, Kreklau EL, Fales KR, Carballares S, Torrres R, Wishart GN, Ajamie RT, Cronier DM, Iversen PW, Meier TI, Foreman RT, Zeckner D, Sissons SE, Halstead BW, Lin AB, Donoho GP, Qian Y, Li S, Wu S, Aggarwal A, Ye XS, Starling JJ, Gaynor RB, de Dios A, Du J. A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models. Mol Cancer Ther. 2014 Jun;13(6):1442-56. doi: 10.1158/1535-7163.MCT-13-0849. Epub 2014 Mar 31. PMID: 24688048.
2. Ou J, Li H, Qiu P, Li Q, Chang HC, Tang YC. CDK9 modulates circadian clock by attenuating REV-ERBα activity. Biochem Biophys Res Commun. 2019 Jun 11;513(4):967-973. doi: 10.1016/j.bbrc.2019.04.043. Epub 2019 Apr 17. PMID: 31005255.
In vitro protocol:
1. Yin T, Lallena MJ, Kreklau EL, Fales KR, Carballares S, Torrres R, Wishart GN, Ajamie RT, Cronier DM, Iversen PW, Meier TI, Foreman RT, Zeckner D, Sissons SE, Halstead BW, Lin AB, Donoho GP, Qian Y, Li S, Wu S, Aggarwal A, Ye XS, Starling JJ, Gaynor RB, de Dios A, Du J. A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models. Mol Cancer Ther. 2014 Jun;13(6):1442-56. doi: 10.1158/1535-7163.MCT-13-0849. Epub 2014 Mar 31. PMID: 24688048.
In vivo protocol:
1. Ou J, Li H, Qiu P, Li Q, Chang HC, Tang YC. CDK9 modulates circadian clock by attenuating REV-ERBα activity. Biochem Biophys Res Commun. 2019 Jun 11;513(4):967-973. doi: 10.1016/j.bbrc.2019.04.043. Epub 2019 Apr 17. PMID: 31005255.
1: Yin T, Lallena MJ, Kreklau EL, Fales KR, Carballares S, Torrres R, Wishart GN,
Ajamie RT, Cronier DM, Iversen PW, Meier TI, Foreman RT, Zeckner D, Sissons SE,
Halstead BW, Lin AB, Donoho GP, Qian Y, Li S, Wu S, Aggarwal A, Ye XS, Starling
JJ, Gaynor RB, de Dios A, Du J. A novel CDK9 inhibitor shows potent antitumor
efficacy in preclinical hematologic tumor models. Mol Cancer Ther. 2014
Jun;13(6):1442-56. doi: 10.1158/1535-7163.MCT-13-0849. Epub 2014 Mar 31. PubMed
PMID: 24688048.
