| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
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Purity: ≥98%
LY2857785 is a novel, potent, selective, 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). As a potent CDK9 inhibitor, LY2857785 has 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.
| ln Vitro |
For 114 protein kinases, LY2857785 shown good selectivity; only 5 other kinases had inhibitory potencies (IC50) less than 0.1 μM, while 14 kinases had inhibitory effects less than 1 μM. With an IC50 of 0.089 (n=13) and 0.042 (n=1) μM, respectively, LY2857785 inhibits CTD P-Ser2 and CTD P-Ser5 in U2OS cells at the cellular level. But with an EC50 of 0.135 μM, LY2857785 only slightly increased the amount of G2-M DNA, from 35% to 55%. The MV-4-11, RPMI8226, and L363 cells exhibited a strong compound exposure and a time-dependent reduction of cell proliferation when exposed to LY2857785. The cell growth inhibitory potency reached its peak effect after 4 to 24 hours of incubation; for MV-4-11, RPMI8226, and L363 cells, the IC50 values were 0.04, 0.2, and 0.5 μM, respectively. LY2857785 induces a time-dependent apoptosis in cancer cells, with a maximum effectiveness of 8 hours in L363 cells and an IC50 of 0.5 μM [1].
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| ln Vivo |
LY2857785 demonstrated strong suppression of RNAP II CTD P-Ser2 in HCT116 xenograft tumor mice, with a dose-dependent TED50 of 4.4 mg/kg and a TEC50 of 0.36 μM. Significant CTD P-Ser2 inhibition was also demonstrated by LY2857785 in HCT116 and MV-4-11 nude mouse xenograft models, with durations of 3 to 6 hours at TED70 (8 mg/kg). Additionally, LY2857785 demonstrated dose-dependent inhibition of CTD P-Ser2 at TED70 (7 mg/kg) and TED90 (10 mg/kg) for eight hours in a nude mouse MV-4-11 xenograft model. In the AML MV-4-11 xenograft tumor model, intravenous bolus injection in mice or intravenous infusion in rats showed the greatest tumor regression when LY2857785 was used [1].
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| References |
| Molecular Formula |
C26H36N6O
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|---|---|
| Molecular Weight |
448.6036
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| Exact Mass |
448.295
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| CAS # |
1619903-54-6
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| PubChem CID |
78357764
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
671.0±65.0 °C at 760 mmHg
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| Flash Point |
359.6±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.672
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| LogP |
3.71
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
606
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LHIUZPIDLZYPRL-MXVIHJGJSA-N
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| 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-
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| 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
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| Synonyms |
LY2857785; LY-2857785; LY 2857785.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~10 mg/mL (~22.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2292 mL | 11.1458 mL | 22.2916 mL | |
| 5 mM | 0.4458 mL | 2.2292 mL | 4.4583 mL | |
| 10 mM | 0.2229 mL | 1.1146 mL | 2.2292 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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