Birabresib
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MedKoo CAT#: 206116

CAS#: 202590-98-5

Description: Birabresib, also known as OTX015 and MK-8628, a potent BET bromodomian inhibitor, which targets the BET bromodomain proteins 2, 3, and 4 (BRD2/3/4). BRDs 2, 3, and 4 are considered potential cancer targets because of their pivotal role in regulating the transcription of growth-promoting genes and cell cycle regulators. OTX015 is the first BRD2/3/4 inhibitor to enter clinical trials. OTX015 showed antiproliferative activity in a large panel of cell lines derived from mature B-cell lymphoid tumors with median IC50 of 240 nmol/L, without significant differences among the different histotypes.


Price and Availability

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Price

10mg
USD 90
100mg
USD 450
1g
USD 2650
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25mg
USD 150
200mg
USD 850
2g
USD 4250
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50mg
USD 250
500mg
USD 1650
5g
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Birabresib, purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order > 4g may be 2 weeks.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206116
Name: Birabresib
CAS#: 202590-98-5
Chemical Formula: C25H22ClN5O2S
Exact Mass: 491.11827
Molecular Weight: 491.99248
Elemental Analysis: C, 61.03; H, 4.51; Cl, 7.21; N, 14.23; O, 6.50; S, 6.52


Related CAS #: 204587-26-8 (dihydrate)   202590-98-5    

Synonym: OTX015; OTX-015; OTX 015; MK-8628; MK 8628; MK8628; Birabresib.

IUPAC/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.

InChi Key: GNMUEVRJHCWKTO-FQEVSTJZSA-N

InChi Code: InChI=1S/C25H22ClN5O2S/c1-13-14(2)34-25-22(13)23(16-4-6-17(26)7-5-16)28-20(24-30-29-15(3)31(24)25)12-21(33)27-18-8-10-19(32)11-9-18/h4-11,20,32H,12H2,1-3H3,(H,27,33)/t20-/m0/s1

SMILES Code: 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


Technical Data

Appearance:
white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Safety Data Sheet (MSDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

 
 
 


References

1: Boi M, Todaro M, Vurchio V, Yang SN, Moon J, Kwee I, Rinaldi A, Pan H, Crescenzo R, Cheng M, Cerchietti L, Elemento O, Riveiro ME, Cvitkovic E, Bertoni F, Inghirami G; AIRC 5xMille Consortium ‘Genetics-Driven Targeted Management of Lymphoid Malignancies’.. Therapeutic efficacy of the bromodomain inhibitor OTX015/MK-8628 in ALK-positive anaplastic large cell lymphoma: an alternative modality to overcome resistant phenotypes. Oncotarget. 2016 Nov 29;7(48):79637-79653. doi: 10.18632/oncotarget.12876. PubMed PMID: 27793034.

2: Vázquez R, Riveiro ME, Astorgues-Xerri L, Odore E, Rezai K, Erba E, Panini N, Rinaldi A, Kwee I, Beltrame L, Bekradda M, Cvitkovic E, Bertoni F, Frapolli R, D'Incalci M. The bromodomain inhibitor OTX015 (MK-8628) exerts anti-tumor activity in triple-negative breast cancer models as single agent and in combination with everolimus. Oncotarget. 2016 Dec 7. doi: 10.18632/oncotarget.13814. [Epub ahead of print] PubMed PMID: 27935867.

3: Coudé MM, Braun T, Berrou J, Dupont M, Bertrand S, Masse A, Raffoux E, Itzykson R, Delord M, Riveiro ME, Herait P, Baruchel A, Dombret H, Gardin C. BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget. 2015 Jul 10;6(19):17698-712. PubMed PMID: 25989842; PubMed Central PMCID: PMC4627339.

4: Riveiro ME, Astorgues-Xerri L, Vazquez R, Frapolli R, Kwee I, Rinaldi A, Odore E, Rezai K, Bekradda M, Inghirami G, D'Incalci M, Noel K, Cvitkovic E, Raymond E, Bertoni F. OTX015 (MK-8628), a novel BET inhibitor, exhibits antitumor activity in non-small cell and small cell lung cancer models harboring different oncogenic mutations. Oncotarget. 2016 Dec 20;7(51):84675-84687. doi: 10.18632/oncotarget.13181. PubMed PMID: 27835869.

5: Berenguer-Daizé C, Astorgues-Xerri L, Odore E, Cayol M, Cvitkovic E, Noel K, Bekradda M, MacKenzie S, Rezai K, Lokiec F, Riveiro ME, Ouafik L. OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models. Int J Cancer. 2016 Nov 1;139(9):2047-55. doi: 10.1002/ijc.30256. PubMed PMID: 27388964.

6: Amorim S, Stathis A, Gleeson M, Iyengar S, Magarotto V, Leleu X, Morschhauser F, Karlin L, Broussais F, Rezai K, Herait P, Kahatt C, Lokiec F, Salles G, Facon T, Palumbo A, Cunningham D, Zucca E, Thieblemont C. Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol. 2016 Apr;3(4):e196-204. doi: 10.1016/S2352-3026(16)00021-1. PubMed PMID: 27063978.

7: Odore E, Lokiec F, Cvitkovic E, Bekradda M, Herait P, Bourdel F, Kahatt C, Raffoux E, Stathis A, Thieblemont C, Quesnel B, Cunningham D, Riveiro ME, Rezaï K. Phase I Population Pharmacokinetic Assessment of the Oral Bromodomain Inhibitor OTX015 in Patients with Haematologic Malignancies. Clin Pharmacokinet. 2016 Mar;55(3):397-405. doi: 10.1007/s40262-015-0327-6. PubMed PMID: 26341814.

8: Balaji N, Chinnapattu M, Dixit A, Sahu P, P S S, Mullangi R. Validation of an enantioselective LC-MS/MS method to quantify enantiomers of (±)-OTX015 in mice plasma: Lack of in vivo inversion of (-)-OTX015 to its antipode. Biomed Chromatogr. 2016 Sep 16. doi: 10.1002/bmc.3853. [Epub ahead of print] PubMed PMID: 27632936.

9: Boi M, Gaudio E, Bonetti P, Kwee I, Bernasconi E, Tarantelli C, Rinaldi A, Testoni M, Cascione L, Ponzoni M, Mensah AA, Stathis A, Stussi G, Riveiro ME, Herait P, Inghirami G, Cvitkovic E, Zucca E, Bertoni F. The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs. Clin Cancer Res. 2015 Apr 1;21(7):1628-38. doi: 10.1158/1078-0432.CCR-14-1561. PubMed PMID: 25623213.

10: Berthon C, Raffoux E, Thomas X, Vey N, Gomez-Roca C, Yee K, Taussig DC, Rezai K, Roumier C, Herait P, Kahatt C, Quesnel B, Michallet M, Recher C, Lokiec F, Preudhomme C, Dombret H. Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study. Lancet Haematol. 2016 Apr;3(4):e186-95. doi: 10.1016/S2352-3026(15)00247-1. PubMed PMID: 27063977.

11: Vázquez R, Licandro SA, Astorgues-Xerri L, Lettera E, Panini N, Romano M, Erba E, Ubezio P, Bello E, Libener R, Orecchia S, Grosso F, Riveiro ME, Cvitkovic E, Bekradda M, D'Incalci M, Frapolli R. Promising in vivo efficacy of the BET bromodomain inhibitor OTX015/MK-8628 in malignant pleural mesothelioma xenografts. Int J Cancer. 2017 Jan 1;140(1):197-207. doi: 10.1002/ijc.30412. PubMed PMID: 27594045.

12: Gaudio E, Tarantelli C, Ponzoni M, Odore E, Rezai K, Bernasconi E, Cascione L, Rinaldi A, Stathis A, Riveiro E, Cvitkovic E, Zucca E, Bertoni F. Bromodomain inhibitor OTX015 (MK-8628) combined with targeted agents shows strong in vivo antitumor activity in lymphoma. Oncotarget. 2016 Sep 6;7(36):58142-58147. doi: 10.18632/oncotarget.10983. PubMed PMID: 27494885; PubMed Central PMCID: PMC5295419.

13: Lu P, Qu X, Shen Y, Jiang Z, Wang P, Zeng H, Ji H, Deng J, Yang X, Li X, Lu H, Zhu H. The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci Rep. 2016 Apr 12;6:24100. doi: 10.1038/srep24100. PubMed PMID: 27067814; PubMed Central PMCID: PMC4828723.

14: Stathis A, Zucca E, Bekradda M, Gomez-Roca C, Delord JP, de La Motte Rouge T, Uro-Coste E, de Braud F, Pelosi G, French CA. Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628. Cancer Discov. 2016 May;6(5):492-500. doi: 10.1158/2159-8290.CD-15-1335. PubMed PMID: 26976114; PubMed Central PMCID: PMC4854801.

15: Henssen A, Althoff K, Odersky A, Beckers A, Koche R, Speleman F, Schäfers S, Bell E, Nortmeyer M, Westermann F, De Preter K, Florin A, Heukamp L, Spruessel A, Astrahanseff K, Lindner S, Sadowski N, Schramm A, Astorgues-Xerri L, Riveiro ME, Eggert A, Cvitkovic E, Schulte JH. Targeting MYCN-Driven Transcription By BET-Bromodomain Inhibition. Clin Cancer Res. 2016 May 15;22(10):2470-81. doi: 10.1158/1078-0432.CCR-15-1449. PubMed PMID: 26631615.

16: Saenz DT, Fiskus W, Qian Y, Manshouri T, Rajapakshe K, Raina K, Coleman KG, Crew AP, Shen A, Mill CP, Sun B, Qiu P, Kadia TM, Pemmaraju N, DiNardo C, Kim MS, Nowak AJ, Coarfa C, Crews CM, Verstovsek S, Bhalla KN. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells. Leukemia. 2017 Jan 31. doi: 10.1038/leu.2016.393. [Epub ahead of print] PubMed PMID: 28042144.

17: Asangani IA, Wilder-Romans K, Dommeti VL, Krishnamurthy PM, Apel IJ, Escara-Wilke J, Plymate SR, Navone NM, Wang S, Feng FY, Chinnaiyan AM. BET Bromodomain Inhibitors Enhance Efficacy and Disrupt Resistance to AR Antagonists in the Treatment of Prostate Cancer. Mol Cancer Res. 2016 Apr;14(4):324-31. doi: 10.1158/1541-7786.MCR-15-0472. PubMed PMID: 26792867; PubMed Central PMCID: PMC4834259.

18: Lin X, Huang X, Uziel T, Hessler P, Albert DH, Roberts-Rapp LA, McDaniel KF, Kati WM, Shen Y. HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues. Mol Cancer Ther. 2017 Feb;16(2):388-396. doi: 10.1158/1535-7163.MCT-16-0475. PubMed PMID: 27903752.

19: Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Hines J, Winkler JD, Crew AP, Coleman K, Crews CM. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Chem Biol. 2015 Jun 18;22(6):755-63. doi: 10.1016/j.chembiol.2015.05.009. PubMed PMID: 26051217; PubMed Central PMCID: PMC4475452.

20: Pérez-Peña J, Serrano-Heras G, Montero JC, Corrales-Sánchez V, Pandiella A, Ocaña A. In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment. Mol Cancer Ther. 2016 Aug;15(8):1823-33. doi: 10.1158/1535-7163.MCT-16-0004. PubMed PMID: 27256375.