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| 2mg |
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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
Birabresib (formerly OTX-015; MK-8628) is a potent and orally bioavailable inhibitor of BET bromodomain (BRD2/3/4) with antineoplastic activity. It inhibits BRD2/3/4 with EC50s in the range of 10 to 19 nM in cell-free assays. OTX 015 is the first BRD2/3/4 inhibitor to enter clinical trials (phase 2) for the treatment of cancer, and is currently in clinical trials for treating leukemia and glioblastoma. OTX015 exhibits excellent antiproliferative activity in a large panel of cell lines derived from mature B-cell lymphoid tumors with median IC50 of 240 nmol/L, and high in vivo antitumor efficacy.
| ln Vitro |
Birabresib (OTX-015) (500 nM) exposure generates a substantial decrease of BRD2, BRD4 and c-MYC and rise of HEXIM1 proteins, whereas BRD3 expression is unaltered. 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) administration promotes HIV-1 full-length transcripts and viral outgrowth in resting CD4+ T cells from infected patients receiving suppressive antiretroviral therapy (ART), while exerting low 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].
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| ln Vivo |
Birabresib (OTX-015) (50 mg/kg) significantly (p?<0.05) reduces tumor burden in MDA-MB-231 murine xenografts when compared to mice given with a vehicle. More effective activity is seen by combining Birabresib (OTX-015) with 2 mg/kg RAD001 than by using Birabresib alone[4].
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| References |
[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 |
| Molecular Formula |
C25H22CLN5O2S
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|---|---|
| Molecular Weight |
491.99
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| CAS # |
202590-98-5
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| Related CAS # |
(R)-Birabresib;1983196-25-3
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| SMILES |
O=C(NC1=CC=C(O)C=C1)C[C@H]2C3=NN=C(C)N3C4=C(C(C)=C(C)S4)C(C5=CC=C(Cl)C=C5)=N2
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| Chemical Name |
(S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide.
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| Synonyms |
MK-8628; MK 8628; Birabresib; OTX015; OTX-015; MK8628; OTX 015
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (6.10 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 (5.08 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. View More
Solubility in Formulation 3: 2.5 mg/mL (5.08 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. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.08 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 corn oil and mix evenly. Solubility in Formulation 5: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL Solubility in Formulation 6: 10 mg/mL (20.33 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 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 |
*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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02259114 | Completed Has Results | Drug: Birabresib | NUT Midline Carcinoma Triple Negative Breast Cancer |
Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) |
October 23, 2014 | Phase 1 |
| NCT02698189 | Terminated Has Results | Drug: Birabresib Dose 20 mg | AML Including AML de Novo and AML Secondary to MDS DLBCL |
Merck Sharp & Dohme LLC | May 19, 2016 | Phase 1 |
| NCT02296476 | Terminated Has Results | Drug: Birabresib | Glioblastoma Multiforme | Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) |
October 29, 2014 | Phase 2 |
| NCT02698176 | Terminated Has Results | Drug: Birabresib | NUT Midline Carcinoma (NMC) Triple Negative Breast Cancer (TNBC) |
Merck Sharp & Dohme LLC | May 4, 2016 | Phase 1 |
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