| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| ln Vitro |
At IC50s of 3950 nM for BRD2 BD2, 1210 nM for BRD3 BD2, 5843 nM for BRD4 BD2, and 17451 nM for BRDDT BD2, GSK778 inhibits BRD BD2 [1]. Human primary CD4+ T cell proliferation and the generation of effector cytokines, such as IFNγ, IL-17A, and IL-22, are inhibited by GSK778 (0.01-10 μM; 72 hours) [1]. The effect of GSK778 (0.001-10 μM; 5 days) on the proliferation and viability of MDA-453, MOLM-13, K562, MV4-11, THP-1, and MDA-MB-231 cells is more pronounced [1]. For MV4-11, MOLM13, MDA-MB-231, and MB453 cells, GSK778 (1000 nM; 72 hours) suppresses proliferation and causes cell cycle arrest as well as apoptosis [1]. Primary human AML cells' ability to proliferate is inhibited by GSK778 (1000 nM; 12 days) [1].
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| ln Vivo |
GSK778 (15mg/kg/BID; i.p. for 30 days) has a higher survival benefit than iBET-BD2 in the aggressive MLL-AF9 AML model [1]. ?GSK778 (15 mg/kg/BID; subcutaneously for 14 days) lowers the generation of anti-keyhole limpet hemocyanin (KLH) IgM and is well tolerated [1]. ?GSK778 demonstrates Cmax (85 ng/mL), Tmax (1.48 h) and AUC∞ (132 ng.h/mL) after oral treatment (10mg/kg) to mice [1].
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| Cell Assay |
Cell proliferation assay [1]
Cell Types: Human primary CD4+ T cells Tested Concentrations: 0.001, 0.01, 0.1, 1, 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited cell proliferative activity and effector cytokine production. Cell viability assay[1] Cell Types: MDA-453, MOLM-13, K562, MV4-11, THP-1 and MDA-MB-231 Cell Tested Concentrations: 0.001, 0.01, 0.1, 1, 10 μM Incubation Duration: 5 days Experimental Results: Inhibition of growth and viability of human cancer cell lines. Apoptosis analysis[1] Cell Types: MV4-11, MOLM13, MDA-MB-231 and MB453 Cell Tested Concentrations: 1000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited cell proliferation and induced cell cycle arrest and apoptosis. |
| Animal Protocol |
Animal/Disease Models: Female C57BL/6 mice 6-8 weeks old were injected with MLL-AF9 cells [1].
Doses: 15 mg/kg/BID. Route of Administration: intraperitoneal (ip) injection for 30 days. Experimental Results: Improved survival rate of leukemia mice. Animal/Disease Models: Male CD1 mice [1] Doses: 10 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Oral administration Experimental Results: Cmax (85 ng/mL), Tmax (1.48 h); AUC∞ (132 ng.h/mL). |
| References |
| Molecular Formula |
C30H33N5O3
|
|---|---|
| Molecular Weight |
511.6147
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| Exact Mass |
511.258
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| CAS # |
2451862-42-1
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| PubChem CID |
146018691
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| Appearance |
White to light yellow solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
38
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| Complexity |
768
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O(C1=C(C2C(C([H])([H])[H])=NOC=2C([H])([H])[H])C([H])=C2C(=C1[H])C1=C(C([H])=N2)N=C(C([H])([H])OC([H])([H])[H])N1[C@]([H])(C([H])([H])[H])C1C([H])=C([H])C([H])=C([H])C=1[H])C([H])([H])[C@]1([H])C([H])([H])N([H])C([H])([H])C1([H])[H]
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| InChi Key |
ZORLJXWXFABTPZ-CTNGQTDRSA-N
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| InChi Code |
InChI=1S/C30H33N5O3/c1-18-29(20(3)38-34-18)24-12-25-23(13-27(24)37-16-21-10-11-31-14-21)30-26(15-32-25)33-28(17-36-4)35(30)19(2)22-8-6-5-7-9-22/h5-9,12-13,15,19,21,31H,10-11,14,16-17H2,1-4H3/t19-,21+/m1/s1
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| Chemical Name |
4-[2-(methoxymethyl)-1-[(1R)-1-phenylethyl]-8-[[(3S)-pyrrolidin-3-yl]methoxy]imidazo[4,5-c]quinolin-7-yl]-3,5-dimethyl-1,2-oxazole
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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 : ~41.67 mg/mL (~81.45 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.07 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 20.8 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: 2.08 mg/mL (4.07 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.07 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 | 1.9546 mL | 9.7731 mL | 19.5461 mL | |
| 5 mM | 0.3909 mL | 1.9546 mL | 3.9092 mL | |
| 10 mM | 0.1955 mL | 0.9773 mL | 1.9546 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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