A Notch inhibitor
LY3039478 is a novel and potent Notch inhibitor with IC50 of 0.41 nM.
The novel and unique Notch Inhibitor, LY3039478, has progressed into clinical development by Lilly co. ltd. LY3039478 displays the best overall profile and is unique within the SAR investigated. LY3039478 Displays Interesting Atropisomer Phenomena. The average LY3039478 major/minor rotational isomer ratio ranged between 14 and 28 in plasma. The crystalline monohydrate form of LY3039478 consists of a single rotational isomer and is chemically and physically stable for at least 14 days under accelerated stability test conditions.
Reference:
[1].Warren J.? Porter. Discovery of a Novel Notch Inhibitor. The 8th SCI-RSC Symposium on Proteinase Inhibitor Design April 15-16, 2013, Basel, Switzerland.
| Cell experiment [1]: | |
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Cell lines |
Normal human kidney tubular epithelial cell line HK2 and renal cell cancer cell lines 786-O, 769-P and Caki |
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Preparation method |
The solubility of this compound in DMSO is >23.2 mg/ml. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0-10 μM |
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Applications |
LY3039478 was found to be able to significantly inhibit the growth of two CCRCC cell lines in a concentration dependent manner. LY3039478 treatment also led to decreased expression of Myc and Cyclin A1, two genes that were part of the NOTCH driven proliferative signature in murine and human model systems. LY3039478 treatment also led to G0/G1 cell cycle arrest in CCRCC cells. |
| Animal experiment [1]: | |
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Animal models |
NSG xenograft mice model with 769-P CCRCC cells |
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Dosage form |
8 mg/kg by oral gavage |
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Application |
LY3039478 treatment resulted in significantly increased survival and delayed tumor growth in independent cohorts of mice demonstrating in vivo efficacy in CCRCC. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1] Bhagat TD et al.Notch Pathway Is Activated via Genetic and Epigenetic Alterations and Is a Therapeutic Target in Clear Cell Renal Cancer. J Biol Chem. 2017 Jan 20;292(3):837-846. | |
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