| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
|
| ln Vitro |
BET bromodomain inhibitor 1 (compound 38; 31.25-125 nM; 24 hr) induces a more prominent G1 cell cycle arrest [1]. It is very successful to induce dose-dependent suppression of c-Myc expression and elevation of p21 levels using BET bromodomain Inhibitor 1 (31.25-500 nM; 6 or 24 hours) [1]. Expressions of c-Myc, BCL-2, and CDK6 are dramatically reduced by BET bromodomain Inhibitor 1 (31.25-125 nM; 6 hours) [1]. Five cytochrome P450 enzymes (IC50>20 μM) are not inhibited by BET bromodomain inhibitor 1 [1]. BET Bromo Domain Inhibitor 1 is around 1500 times more selective for BRD4(1) than EP300 (IC50=3857 nM), and it shows good selectivity for the BET Bromo domain family over other Bromo domains[1]. With an IC50 value of 2.4, 4.8, 17.6, and 15.1 nM, respectively, BET bromodomain inhibitor 1 significantly inhibits the proliferation of acute myeloid leukemia cell line MV4-11, acute leukemia cell lines Kasumi-1 and RS-4-11, and multiple myeloma cancer cell line MM1.S cells[1].
|
|---|---|
| ln Vivo |
Compound 38, orally administered daily for 28 days, exhibited a greater anticancer efficacy and totally suppressed tumor development at 6.25 and 12.5 mg/kg of BET bromodomain inhibitor 1. (TGI) is 99.7%. [1]. For rats and mice, respectively, BET bromodomain inhibitor 1 (1 mg/kg; IV) showed T1/2 of 1.3 and 0.9 hours, CL of 21.5 and 15.3 mL/min·kg, and Vss of 1464 and 15.3 mL/min·kg [1]. Rats treated orally with BET bromodomain inhibitor 1 (3 mg/kg) had an AUC of 884 ng·h/mL, a Cmax of 159 ng/mL, and a T1/2 of 3.6 hours [1]. The oral BET bromodomain inhibitor 1 (1.3 mg/kg) has an AUC of 1710 ng·h/mL in mice, a T1/2 of 1.3 hours, and a Cmax of 399 ng/mL [1].
|
| Cell Assay |
Cell cycle analysis[1]
Cell Types: MV-4-11 Cell Tested Concentrations: 31.25, 62.5, 125 nM Incubation Duration: 24 hrs (hours) Experimental Results: Result in more obvious G1 phase cell cycle arrest. Western Blot Analysis[1] Cell Types: MV-4-11 Cell Tested Concentrations: 31.25, 62.5, 125, 250, 500 nM Incubation Duration: 6 or 24 hrs (hours) Experimental Results: Induction of dose-dependent inhibition of c-Myc expression and upregulation of p21 levels. RT-PCR[1] Cell Types: MV-4-11 Cell Tested Concentrations: 31.25, 62.5, 125 nM Incubation Duration: 6 hrs (hours) Experimental Results: Dramatically diminished expression of c-Myc, BCL-2 and CDK6. |
| Animal Protocol |
Animal/Disease Models: MV4-11 mouse xenograft model [1]
Doses: 6.25, 12.5 mg/kg Route of Administration: oral; daily; 28-day Experimental Results: demonstrated stronger anti-tumor activity and completely inhibited tumor growth, The tumor growth inhibition (TGI) was 99.7% at 12.5 mg/kg. Animal/Disease Models: Male SD rat[1] Doses: 1 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)injection Experimental Results: T1/2 is 1.3 hrs (hrs (hours)), CL is 21.5 mL/min·kg, Vss is 1464 mL/kg. |
| References |
| Molecular Formula |
C22H19F2N3O4S
|
|---|---|
| Molecular Weight |
459.47
|
| Exact Mass |
459.106
|
| CAS # |
2411226-02-1
|
| PubChem CID |
146047136
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
821
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCS(=O)(CC1C=NC(OC2C=CC(=CC=2F)F)=C(C2=CC(C)=C3C(NC=CN23)=O)C=1)=O
|
| InChi Key |
UETQFSCWDMJWMM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H19F2N3O4S/c1-3-32(29,30)12-14-9-16(18-8-13(2)20-21(28)25-6-7-27(18)20)22(26-11-14)31-19-5-4-15(23)10-17(19)24/h4-11H,3,12H2,1-2H3,(H,25,28)
|
| Chemical Name |
6-[2-(2,4-difluorophenoxy)-5-(ethylsulfonylmethyl)pyridin-3-yl]-8-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~136.03 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.53 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.53 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1764 mL | 10.8821 mL | 21.7642 mL | |
| 5 mM | 0.4353 mL | 2.1764 mL | 4.3528 mL | |
| 10 mM | 0.2176 mL | 1.0882 mL | 2.1764 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
