LY2857785
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406759

CAS#: 1619903-54-6

Description: LY2857785 is a potent CDK9 inhibitor with potential anticancer activity. LY2857785 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. LY2857785 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. The inhibition of CDK9 may represent a promising approach as a cancer therapeutic target, especially in hematologic malignancies.


Chemical Structure

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LY2857785
CAS# 1619903-54-6

Theoretical Analysis

MedKoo Cat#: 406759
Name: LY2857785
CAS#: 1619903-54-6
Chemical Formula: C26H36N6O
Exact Mass: 448.30
Molecular Weight: 448.615
Elemental Analysis: C, 69.61; H, 8.09; N, 18.73; O, 3.57

Price and Availability

Size Price Availability Quantity
5mg USD 350 2 Weeks
25mg USD 950 2 Weeks
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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

Appearance: Solid powder

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

More Info:

Product Data:
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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 16.5 36.78
Ethanol 42.0 93.62

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.

Recalculate based on batch purity %
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.

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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.