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Purity: ≥98%
LY3200882 is a next generation, ATP competitive, potent, highly selective small molecule inhibitor of TGF-β receptor type 1 (TGFβRI). It inhibits the serine-threonine kinase domain of TGFβRI. LY3200882 inhibits various pro-tumorigenic activities. LY3200882 potently inhibits TGFβ mediated SMAD phosphorylation in vitro in tumor and immune cells and in vivo in subcutaneous tumors in a dose dependent fashion. In preclinical tumor models, LY3200882 showed potent anti-tumor activity in the orthotopic 4T1-LP model of triple negative breast cancer and this activity correlated with enhanced tumor infiltrating lymphocytes in the tumor microenvironment.
ln Vitro |
LY3200882 potently suppresses TGFβ induced SMAD phosphorylation in vitro in tumor and immunological cells in a dosage dependent fashion[1]. LY3200882 exhibits potent anti-tumor action in the orthotopic 4T1-LP model of triple negative breast cancer and this activity correlates with augmented tumor infiltrating lymphocytes in the tumor microenvironment[1]. In in vitro immune suppression experiments, LY3200882 has showed the ability to rescue TGFβ1 suppressed or T regulatory cell suppressed naive T cell activity and restore proliferation[1]. LY3200882 decreases NIH3T3 cell viability with an IC50 of 82.9 nM[2].
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ln Vivo |
Treatment with LY3200882 (60 mg/kg; oral gavage; twice daily; 21 days; female BALB/C mice) dramatically slows the formation of tumors in the CT26 model[2]. In vivo, LY3200882 significantly and dose-dependently suppresses TGFβ-mediated SMAD phosphorylation in subcutaneous tumors[1]. In an experimental metastasis tumor model (intravenous EMT6-LM2 model of triple negative breast cancer), LY3200882 has demonstrated anti-metastatic efficacy in vivo[1].
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Animal Protocol |
Animal/Disease Models: BALB/C female mice (5-8 weeks old) injected with CT26 cells[2]
Doses: 60 mg/kg Route of Administration: po (oral gavage); twice a day; for 21 days Experimental Results: A statistically significant tumor growth delay in CT26 model was observed. |
References |
[1]. Huaxing Pei, et al. Abstract 955: LY3200882, a novel, highly selective TGFβRI small molecule inhibitor. AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 955.
[2]. Xu G, et al. Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-β type 1 receptor inhibitors. Eur J Med Chem. 2020 Apr 29;198:112354. |
Molecular Formula |
C24H29N5O3
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Molecular Weight |
435.53
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CAS # |
1898283-02-7
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SMILES |
O1CCC(CC1)C1C(=CN(C2CC2)N=1)OC1C=CN=C(C=1)NC1C=CN=C(C=1)C(C)(C)O
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Chemical Name |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (5.74 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 25.0 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: ≥ 2.5 mg/mL (5.74 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 | 2.2961 mL | 11.4803 mL | 22.9605 mL | |
5 mM | 0.4592 mL | 2.2961 mL | 4.5921 mL | |
10 mM | 0.2296 mL | 1.1480 mL | 2.2961 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.