Birabresib (OTX015)

Name: Birabresib (OTX015)
Brand: Selleck Chemicals
SKU: S7360
Rating: 5 (37 reviews)

For research use only.

Catalog No.S7360 Synonyms: MK 8628

37 publications

Molecular Weight(MW): 491.99

OTX015 is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Phase 1.

Selleck's Birabresib (OTX015) has been cited by 37 publications

Nat Med, 2017, 23(4):493-500

PubMed: 28263307 ( click the link to review the publication )

Nat Med, 2017, 23(9):1046-1054

PubMed: 28805821 ( click the link to review the publication )

Cancer Cell, 2017, 31(5):635-652

PubMed: 28434841 ( click the link to review the publication )

Nat Commun, 2020, 22;11(1):1935

PubMed: 32321921 ( click the link to review the publication )

Nat Commun, 2020, 14;11(1):1833

PubMed: 32286255 ( click the link to review the publication )

Clin Cancer Res, 2020, 20 pii: clincanres

PubMed: 32312893 ( click the link to review the publication )

Cancer Lett, 2020, 1;479:71-88

PubMed: 32200036 ( click the link to review the publication )

Cell Oncol (Dordr), 2020, 10.1007/s13402-020-00497-6

PubMed: 32166583 ( click the link to review the publication )

Int J Oncol, 2020, 56(6):1429-1441

PubMed: 32236593 ( click the link to review the publication )

Transl Oncol, 2020, 13(2):221-232

PubMed: 31869746 ( click the link to review the publication )

Sci Transl Med, 2019, 11(497)

PubMed: 31217338 ( click the link to review the publication )

Blood, 2019, 134(21):1821-1831

PubMed: 31527074 ( click the link to review the publication )

Leukemia, 2019, 33(6):1373-1386

PubMed: 30575820 ( click the link to review the publication )

Cancer Res, 2019, 79(19):4869-4881

PubMed: 31311807 ( click the link to review the publication )

J Hematol Oncol, 2019, 12(1):73

PubMed: 31288832 ( click the link to review the publication )

J Exp Clin Cancer Res, 2019, 38(1):383

PubMed: 31470872 ( click the link to review the publication )

Cell Death Dis, 2019, 10(8):557

PubMed: 31324754 ( click the link to review the publication )

Mol Cancer Ther, 2019, 18(2):235-244

PubMed: 30446586 ( click the link to review the publication )

Sci Rep, 2019, 9(1):3823

PubMed: 30846826 ( click the link to review the publication )

Int J Mol Sci, 2019, 20(17)

PubMed: 31480735 ( click the link to review the publication )

Leuk Res, 2019, 77:42-50

PubMed: 30642575 ( click the link to review the publication )

Clin Cancer Res, 2018, 10.1158/1078-0432.CCR-18-1040

PubMed: 30037819 ( click the link to review the publication )

Clin Cancer Res, 2018, 24(16):3941-3954

PubMed: 29764852 ( click the link to review the publication )

J Exp Clin Cancer Res, 2018, 37(1):241

PubMed: 30285808 ( click the link to review the publication )
J Virol, 2018, 92(2)

PubMed: 29118124 ( click the link to review the publication )

Sci Rep, 2018, 8(1):3521

PubMed: 29476067 ( click the link to review the publication )

Leukemia, 2018, 32(12):2590-2603

PubMed: 29795241 ( click the link to review the publication )

Nucleic Acids Res, 2017, 45(14):8403-8410

PubMed: 28854735 ( click the link to review the publication )

Oncoimmunology, 2017, 7(3):e1398874

PubMed: 29399399 ( click the link to review the publication )

Mol Cancer Ther, 2017, 16(2):285-299

PubMed: 27980108 ( click the link to review the publication )

Mol Cell Proteomics, 2017, mcp.M116.065375

PubMed: 28237943 ( click the link to review the publication )

Biomed Chromatogr, 2017, 31(4)

PubMed: 27632936 ( click the link to review the publication )

Oncotarget, 2017, 8(18):29558-29573

PubMed: 28418907 ( click the link to review the publication )

Oncotarget, 2017, 8(23):37140-37153

PubMed: 28415755 ( click the link to review the publication )

Nucleic Acids Res, 2016, 45(6):3130-3145

PubMed: 27980063 ( click the link to review the publication )

J Hematol Oncol, 2016, 9(1):134

PubMed: 27903272 ( click the link to review the publication )

Sci Rep, 2016, 6:24100

PubMed: 27067814 ( click the link to review the publication )

Purity & Quality Control

Choose Selective Epigenetic Reader Domain Inhibitors

Biological Activity

Description

OTX015 is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Phase 1.

Features

Orally bioavailable BRD2/3/4-selective inhibitor that has been tested in Phase I clinical trials for treatment of Haematological Malignancies.

Targets

BRDs ^[1]
(Cell-free assay)

10-19 nM(EC50)

In vitro

OTX015 inhibits the binding of BRD2, BRD3, and BRD4 to AcH4 with IC50 ranging from 92 to 112 nM, and inhibits the growth of a variety of human cancer cell lines with GI50 ranging from 60 to 200 nM. ^[1] OTX015 results in rapid down-regulation of c-MYC expression, and show the synergistic anti-proliferative effects in combination with ALK inhibitors in ALKpos ALCL cell lines. ^[2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
Rosetta2 DE3 cells	MljHSpVv[3Srb36gZZN{[Xl?		MojON\|AhdWmwcx?=		NFvuSmNFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEN{BDTDJiKEOwOkB1dyB2MUegZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2l;NDDuUS=>	MYeyOlA5ODB4NB?=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	BRD4; PubMed: 26051217 Chem Biol Small molecule BRD4 inhibitors lead to significant BRD4 accumulation. Namalwa and Ramos cells were treated overnight with increasing doses of JQ1 and OTX015. Lysates were collected and subjected to immunoblot analysis with antibodies for BRD4 and actin. c-Myc; PubMed: 26051217 Chem Biol Small molecule BRD4 inhibitors lead to downstream c-MYC suppression, but not efficiently. Namalwa cells were treated overnight with increasing doses of JQ1 and OTX015, lysates were collected and analyzed by immunoblot with antibodies for c-MYC and actin. JAK2 / p-STAT5 / STAT5 / p-STAT3 / c-Myc / PIM1 / CDK6 / HEXIM1 / p27 / p21 / Bcl-xL / γH2AX; PubMed: 28042144 Leukemia SET-2 cells were treated with the indicated concentrations of ARV-825 or OTX015 for 18 hours. Total cell lysates were prepared and immunoblot analyses were conducted as indicated. The expression levels of β-Actin in the cell lysates served as the loading 䲧疝Ỵ疞 ZO-1 / Vimentin; PubMed: 27980063 Nucleic Acids Res JQ1/OTX015 treatment results in decreased expression of the epithelial marker ZO-1 and an increase in mesenchymal marker Vimentin as shown by Western blot analyses of whole cell protein lysates.	26051217 28042144 27980063
Immunofluorescence	BRD4 ; PubMed: 28042144 Leukemia SET2 cells were treated with the indicated concentrations of ARV-825 or OTX015 for 16 hours. Then, cells were cytospun onto glass slides and immunostained for BRD4 expression. Cells were counterstained with DAPI and images were acquired utilizing confocal䲧疝Ỵ疞㧀疜膉痘 瘿뙠ෆᾰƌෆĀ 㺣痖 Vimentin; PubMed: 27980063 Nucleic Acids Res Immunofluorescence staining of Vimentin following JQ1/OTX015 treatment confirms a decreased epithelial phenotype.	28042144 27980063

In vivo

OTX015 (p.o.) significantly inhibits the growth of Ty82 BRD-NUT midline carcinoma tumors in nude mice by 79% at 100 mg/kg qd and 61% at 10 mg/kg bid, respectively. ^[1]

Protocol

Kinase Assay: ^[1]	- Collapse TR-FRET Assay ^[1]: To assess binding of OTX015 to BRD2, BRD3, and BRD4, BRD-expressing CHO cell lysate (from CHO cells transfected with expression plasmids for Flag-tagged BRD2, BRD3, or BRD4 or vector alone), europium-conjugated anti-Flag antibody, XL-665-conjugated streptavidin, and biotinylated OTX015 are incubated at room temperature for 0.2 to 2 h. Fluorescence is measured by TR-FRET using an EnVision 2103 Multilabel Reader and EC50 for binding is calculated by nonlinear regression using PRISM version 5.02.
Cell Research: ^[1]	- Collapse Cell lines: Human tumor cells Concentrations: ~2 μM Incubation Time: 72 hours Method: Effects of OTX015 on cancer cell proliferation are evaluated by incubating human tumor cells for 72 h with increasing concentrations of OTX015 and assessing proliferation using a tetrazolium salt (WST-8)-based colorimetric assay. (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: BLAB/c-nu/nu mice bearing established Ty82 BRD-NUT midline carcinoma xenografts. Dosages: ~100 mg/kg Administration: p.o. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	98 mg/mL (199.19 mM)
	Ethanol	98 mg/mL (199.19 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing.	5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Birabresib (OTX015) SDF

Molecular Weight	491.99
Formula	C₂₅H₂₂ClN₅O₂S
CAS No.	202590-98-5
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	MK 8628
Smiles	CC1=C(C)C2=C(S1)[N]3C(=NN=C3C(CC(=O)NC4=CC=C(O)C=C4)N=C2C5=CC=C(Cl)C=C5)C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

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Calculation results:

Working concentration： mg/ml；

Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid 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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

Molarity Calculator

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Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

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Computed Result

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Molecular Weight Calculator

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Birabresib (OTX015)