| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
GSK 525768A is the inactive enantiomer of GSK525762A, and has no activity towards BET. Lysine acetylation is a key mechanism that regulates chromatin structure; aberrant acetylation levels have been linked to the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are small interaction modules found on diverse proteins, some of which have a key role in the acetylation-dependent assembly of transcriptional regulator complexes.
| Targets |
BET (no activity; inactive enantiomer of GSK525762A)
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|---|---|
| ln Vitro |
In relation to BET, GSK 525768A is inactive[1]. The (R)-enantiomer of GSK 525762A is GSK 525768A (GSK525768A). GSK525762A was found to alter levels of high-density lipoprotein apolipoprotein A1 (APOA1) in a test that monitored APOA1 release in hepatocytes, but the (R)-enantiomer (GSK 525768A) had no impact. GSK 525768A mimics the binding mode of acetylated lysine by directly engaging protein modules through the formation of hydrogen bonds with conserved asparagine residues. This frequently leads to the inhibitor binding deeper into the acetylated lysine binding site, but it does not replace the conserved water molecules that are present at the bottom of the acetyl-lysine binding cavity [2].
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| ln Vivo |
We then examined the necessity of the cell death modulated by Bim for the anticancer function of GEM/gemcitabine and I-BET762 in xenograft mice. In Panc-1 tumor-bearing mice, GEM and I-BET762 decreased the tumor weight and volume. The combination of GEM and I-BET762 triggered a remarkable decline in tumor weight and volume compared with that of either agent alone (Fig. 6A). TUNEL and Ki67 assays indicated that I-BET762 and GEM induced less apoptosis when used alone than did the combination treatment (Fig. 6B and C). In contrast, compared with the parental tumors, Bim-KD tumors showed noticeably weaker growth suppression in response to the combination therapy (Fig. 6A–C). Furthermore, to evaluate the toxicity effects of I-BET762 and the combination of I-BET762 and GEM on mice, we measured ALT, AST and BUN levels after treatment. We found that I-BET762 did not influence the ALT or AST in serum samples or their GEM-induced elevation. BUN was not affected by any therapy mentioned above (Fig. 6D).[3]
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| Animal Protocol |
BALB/c nude mice were subcutaneously injected with pancreatic cancer cells in their right flanks. When the tumor volume reached 150–200 mm3, 24 tumor-bearing mice were randomly divided into 4 groups (I-BET762, GEM, both, and control). The mice in the GEM group were injected with GEM (25 mg/kg/day) through the caudal vein every 3 days for 13 days, and those in the I-BET762 group received an intraperitoneal injection of I-BET762 (30 mg/kg/day) daily for 13 days. The mice in the combination group were treated with both I-BET762 (30 mg/kg/day) and GEM (25 mg/kg/day). In the control group, mice were treated with an equivalent amount of vehicle. Changes in body weight were monitored throughout the experiment. Tumor growth was measured every other day according to the following formula: tumor volume = length × width2/2. Mice were sacrificed on day 22 of the treatment. The tumors were excised and weighed, and the tumor volume was measured. Finally, 0.5 ml of blood was drawn from every mouse by cardiac puncture and was sent to clinical laboratories to evaluate the hepatic and renal activities.[5]
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| References |
[1]. Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468(7327):1119-23.
[2]. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat Rev Drug Discov. 2014 May;13(5):337-56. [3]. RETRACTED ARTICLE: The BET inhibitor I-BET762 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine. Sci Rep. 2018; 8: 8102. |
| Molecular Formula |
C22H22CLN5O2
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|---|---|
| Molecular Weight |
423.8954
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| Exact Mass |
423.146
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| Elemental Analysis |
C, 62.34; H, 5.23; Cl, 8.36; N, 16.52; O, 7.55
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| CAS # |
1260530-25-3
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| Related CAS # |
Molibresib;1260907-17-2
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| PubChem CID |
52934127
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| Appearance |
Typically exists as Light yellow to yellow solids at room temperature
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| LogP |
3.931
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
639
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])C1C2C([H])=C(C([H])=C([H])C=2N2C(C([H])([H])[H])=NN=C2[C@@]([H])(C([H])([H])C(N([H])C([H])([H])C([H])([H])[H])=O)N=1)OC([H])([H])[H]
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| InChi Key |
AAAQFGUYHFJNHI-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C22H22ClN5O2/c1-4-24-20(29)12-18-22-27-26-13(2)28(22)19-10-9-16(30-3)11-17(19)21(25-18)14-5-7-15(23)8-6-14/h5-11,18H,4,12H2,1-3H3,(H,24,29)/t18-/m1/s1
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| Chemical Name |
2-[(4R)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide
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| Synonyms |
GSK-525768A; GSK525768A; GSK 525768A; 1260530-25-3; 2-[(4R)-6-(4-Chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide; GSK525768A; GSK525762A(Molibresib I-BET762); CHEMBL2153435; SCHEMBL12966358; DTXSID50680634; GSK 525768A
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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 : ≥ 100 mg/mL (~235.90 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.90 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 (5.90 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3590 mL | 11.7952 mL | 23.5905 mL | |
| 5 mM | 0.4718 mL | 2.3590 mL | 4.7181 mL | |
| 10 mM | 0.2359 mL | 1.1795 mL | 2.3590 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.
 I-BET is a selective antagonist of BET proteins.Nature.2010 Dec 23;468(7327):1119-23. |
|---|
 I-BET suppresses a specific subset of LPS-inducible genes.Nature.2010 Dec 23;468(7327):1119-23. |
 Epigenetic profiles of genes suppressed or unaffected by I-BET in LPS-stimulated macrophages.Nature.2010 Dec 23;468(7327):1119-23. |
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