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| Product Name: | GSK778 | | Synonyms: | 1H-Imidazo[4,5-c]quinoline, 7-(3,5-dimethyl-4-isoxazolyl)-2-(methoxymethyl)-1-[(1R)-1-phenylethyl]-8-[(3S)-3-pyrrolidinylmethoxy]-;iBET-BD1 dihydrochloride;GSK778;GSK778（iBET-BD1 dihydrochloride）;2451862-42-1;iBET-BD1 dihydrochloride (GSK778);GSK778|||GSK 778|||GSK-778;4-[2-(methoxymethyl)-1-[(1R)-1-phenylethyl]-8-{[(3S)-pyrrolidin-3-yl]methoxy}-1H-imidazo[4,5-c]quinolin-7-yl]-3,5-dimethyl-1,2-oxazole | | CAS: | 2451862-42-1 | | MF: | C30H33N5O3 | | MW: | 511.61 | | EINECS: | | | Product Categories: | | | Mol File: | 2451862-42-1.mol |  |
| | GSK778 Chemical Properties |
| Boiling point | 679.6±55.0 °C(Predicted) | | density | 1.31±0.1 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | DMSO : 41.67 mg/mL (81.45 mM; Need ultrasonic) | | pka | 9.90±0.10(Predicted) | | form | Solid | | color | White to light yellow | | InChIKey | ZORLJXWXFABTPZ-CTNGQTDRSA-N | | SMILES | N1C2C(=CC(OC[C@H]3CCNC3)=C(C3=C(C)ON=C3C)C=2)C2N([C@@H](C3=CC=CC=C3)C)C(COC)=NC=2C=1 |
| | GSK778 Usage And Synthesis |
| Uses | GSK778 (iBET-BD1) is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC50s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. GSK778 phenocopies the effects of pan-BET inhibitors in cancer models[1]. | | in vivo | GSK778 (15mg/kg/BID; i.p. for 30 days) offers a superior survival advantage to iBET-BD2 in the aggressive MLL-AF9 AML model[1].
GSK778 (15mg/kg/BID; s.c. for 14 days) reduces the production of anti-keyhole limpet hemocyanin (KLH) IgM and is well tolerated[1].
GSK778 exhibits Cmax (85 ng/mL), Tmax (1.48 h) and AUC∞ (132 ng.h/mL) following oral administration (10mg/kg) in mice[1]. | Animal Model: | 6-8 weeks female C57BL/6 mice are injected with MLL-AF9 cells[1] | | Dosage: | 15mg/kg/BID | | Administration: | I.p. injections for 30 days | | Result: | Increased the survival rate of leukemia mice. |
| Animal Model: | Male CD1 mice[1] | | Dosage: | 10mg/kg (Pharmacokinetic Analysis) | | Administration: | P.o. administration | | Result: | Cmax (85 ng/mL), Tmax (1.48 h); AUC∞ (132 ng.h/mL). |
| | IC 50 | BRD2 BD1: 75 nM (IC50); BRD3 BD1: 41 nM (IC50); BRD4 BD1: 41 nM (IC50); BRDT BD1: 143 nM (IC50) | | References | [1] Omer G, et, al. Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation. Science. 2020 Apr 24; 368(6489): 387-394. DOI:10.1126/science.aaz8455 |
| | GSK778 Preparation Products And Raw materials |
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