Birabresib (OTX-015) is a potent bromodomain (BRD2/3/4) inhibitor with IC50s ranging from 92 to 112 nM.
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Birabresib Estructura química
No. CAS : 202590-98-5
This product is a controlled substance and not for sale in your territory.
Based on 30 publication(s) in Google Scholar
Other Forms of Birabresib:
(R)-Birabresib
In-stock
Birabresib purchased from MedChemExpress. Usage Cited in:
Cancer Res. 2019 May 15;79(10):2761-2774.
[Abstract]
BETi dampens signaling downstream of receptor tyrosine kinases. Western blotting of HER3 and downstream effectors in response to increasing doses of OTX015 at 24h. SCCOHT1, OVK18: SCCOHT cells; OVCAR8, SKOV3, and IGROV1, serous ovarian carcinoma cells.
Birabresib purchased from MedChemExpress. Usage Cited in:
Cancer Res. 2019 May 15;79(10):2761-2774.
[Abstract]
Western blot analysis of HER3 in SCCOHT1 cells after re-expression and dose-dependent treatment with OTX015 at 24h.
NRAS-mutant melanoma cells grown as collagen-embedded 3D spheroids are treated with DMSO, 0.1 μM MEKi PD901, 0.5 μM BETi (JQ-1 or OTX-015), or BETi+MEKi combination for 5 days. Spheroids are stained with Calcein (AM) (green; live cells) and EtBr (red; dead cells) and imaged using a fluorescence microscope.
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Descripciòn
Birabresib (OTX-015) is a potent bromodomain (BRD2/3/4) inhibitor with IC50s ranging from 92 to 112 nM.
IC50 & Target
IC50: 92-112 nM (BRD2, BRD3, BRD4)[1]
In Vitro
Birabresib (OTX-015) (500 nM) exposure induces a strong decrease of BRD2, BRD4 and c-MYC and increase of HEXIM1 proteins, while BRD3 expression is unchanged. c-MYC, BRD2, BRD3, BRD4?and?HEXIM1?mRNA levels do correlate however with viability following exposure to Birabresib (OTX-015)[2].?Birabresib (OTX-015) (0.1, 1, 5 μM) treatment induces HIV-1 full-length transcripts and viral outgrowth in resting CD4+ T cells from infected individuals receiving suppressive antiretroviral therapy (ART), while exerting minimal toxicity and effects on T cell activation. Birabresib-mediated activation of HIV-1 involves an increase in CDK9 occupancy and RNAP II C-terminal domain (CTD) phosphorylation[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Birabresib Related Antibodies
In Vivo
In MDA-MB-231 murine xenografts, tumor mass is significantly (p?< 0.05) reduced by Birabresib (OTX-015) (50 mg/kg) with respect to vehicle-treated animals. Birabresib (OTX-015) in combination with 2 mg/kg RAD001 shows more effective activity than Birabresib alone[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Almacenamiento
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
2 years
-20°C
1 year
Solvente y solubilidad
In Vitro:
DMSO : ≥ 49 mg/mL (99.60 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
*"≥" means soluble, but saturation unknown.
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.0326 mL
10.1628 mL
20.3256 mL
5 mM
0.4065 mL
2.0326 mL
4.0651 mL
10 mM
0.2033 mL
1.0163 mL
2.0326 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: ≥ 3 mg/mL (6.10 mM); Clear solution
Protocol 2
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.08 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 3
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.08 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 4
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.08 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 10 mg/mL (20.33 mM); Clear solution; Need ultrasonic and warming and heat to 60°C
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. J. Kay Noel, et al. Abstract C244: Development of the BET bromodomain inhibitor OTX015. Mol Cancer Ther November 2013 12; C244.
[2]. Marie-Magdelaine Coudé, et al. BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget. 2015 Jul 10; 6(19): 17698–17712.
[3]. Lu P, et al. The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci Rep. 2016 Apr 12;6:24100
[4]. Vázquez R, et al. The bromodomain inhibitor OTX015 (MK-8628) exerts anti-tumor activity in triple-negative breast cancer models as single agent and in combination with RAD001. Oncotarget. 2017 Jan 31;8(5):7598-7613.
[Content Brief]
Ensayo celular
[2]
For the MTT assay, cells are seeded in 24-well plates at 1×106 per well and treated with Birabresib (OTX-015) (0.01 nM-10 μM) for 72 h. Cells are transferred to 96-well plates and incubated with 0.5 mg/mL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) in the dark at 37°C for 4 h. Cells are then lysed with 25% sodium dodecyl sulfate (SDS) lysis buffer and absorbance is read at 570 nm using a Microplate Reader. Three independent experiments are run for each cell line and untreated cells are used as negative controls.
MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Administraciòn de animales
[4]
Mice are subcutaneously injected in the right flank with 10×106 MDA-MB-231 cells. When average tumor weight is appr 130 mg, mice are randomized (nine animals/group) to one of the following experimental groups: vehicle (for Birabresib (OTX-015), water, twice daily, oral; for RAD001 vehicle, 5% Tween-80/5% polyethylene glycol 400, thrice weekly, intraperitoneal); 50 mg/kg Birabresib (OTX-015), twice daily, oral; 2 mg/kg RAD001, thrice weekly, intraperitoneal; 50 mg/kg Birabresib (OTX-015) + 2 mg/kg RAD001, according to the single agent dosing schedules.
MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Referencias
[1]. J. Kay Noel, et al. Abstract C244: Development of the BET bromodomain inhibitor OTX015. Mol Cancer Ther November 2013 12; C244.
[2]. Marie-Magdelaine Coudé, et al. BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget. 2015 Jul 10; 6(19): 17698–17712.
[3]. Lu P, et al. The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci Rep. 2016 Apr 12;6:24100
[4]. Vázquez R, et al. The bromodomain inhibitor OTX015 (MK-8628) exerts anti-tumor activity in triple-negative breast cancer models as single agent and in combination with RAD001. Oncotarget. 2017 Jan 31;8(5):7598-7613.
[Content Brief]
[1]. J. Kay Noel, et al. Abstract C244: Development of the BET bromodomain inhibitor OTX015. Mol Cancer Ther November 2013 12; C244.
[2]. Marie-Magdelaine Coudé, et al. BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget. 2015 Jul 10; 6(19): 17698–17712.
[3]. Lu P, et al. The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci Rep. 2016 Apr 12;6:24100
[4]. Vázquez R, et al. The bromodomain inhibitor OTX015 (MK-8628) exerts anti-tumor activity in triple-negative breast cancer models as single agent and in combination with RAD001. Oncotarget. 2017 Jan 31;8(5):7598-7613.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
2.0326 mL
10.1628 mL
20.3256 mL
50.8140 mL
5 mM
0.4065 mL
2.0326 mL
4.0651 mL
10.1628 mL
10 mM
0.2033 mL
1.0163 mL
2.0326 mL
5.0814 mL
15 mM
0.1355 mL
0.6775 mL
1.3550 mL
3.3876 mL
20 mM
0.1016 mL
0.5081 mL
1.0163 mL
2.5407 mL
25 mM
0.0813 mL
0.4065 mL
0.8130 mL
2.0326 mL
30 mM
0.0678 mL
0.3388 mL
0.6775 mL
1.6938 mL
40 mM
0.0508 mL
0.2541 mL
0.5081 mL
1.2704 mL
50 mM
0.0407 mL
0.2033 mL
0.4065 mL
1.0163 mL
60 mM
0.0339 mL
0.1694 mL
0.3388 mL
0.8469 mL
80 mM
0.0254 mL
0.1270 mL
0.2541 mL
0.6352 mL
Birabresib Related Classifications
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.