Birabresib dihydrate

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 414656

CAS#: 204587-26-8 (dihydrate)

Description: Birabresib dihydrate was initially developed by Mitsubishi Tanabe Pharma Corporation, but then was licensed by OncoEthix, privately held biotechnology company. OTX015 is a selective bromodomains: BRD2, BRD3, and BRD4 inhibitor and inhibits their binding to AcH4. Bromodomains have an important role in the targeting of chromatin-modifying enzymes to specific sites, including methyltransferases, HATs and transcription factors and regulate diverse biological processes from cell proliferation and differentiation to energy homeostasis and neurological processes. OTX015 has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models. Oral administration of OTX-015 markedly inhibited tumor growth and reduced tumor volume. OTX015 is currently in Phase 1b studies for the treatment of hematological malignancies and advanced solid tumors such as Triple Negative Breast Cancer, Non-small Cell Lung Cancer, Castrate-resistant Prostate Cancer (CRPC) and Pancreatic Ductal Adenocarcinoma. In addition, OTX015 was in phase II for the treatment of Glioblastoma Multiforme, but there were not detected clinical activity of the drug in the treatment populations and trial was closed.

Chemical Structure

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Birabresib dihydrate
CAS# 204587-26-8 (dihydrate)
Instruction

Theoretical Analysis

MedKoo Cat#: 414656
Name: Birabresib dihydrate
CAS#: 204587-26-8 (dihydrate)
Chemical Formula: C25H26ClN5O4S
Exact Mass: 527.14
Molecular Weight: 528.020
Elemental Analysis: C, 56.87; H, 4.96; Cl, 6.71; N, 13.26; O, 12.12; S, 6.07

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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

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

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 dihydrate

InChi Key: LZLFEVJSMKCZGE-FJSYBICCSA-N

InChi Code: InChI=1S/C25H22ClN5O2S.2H2O/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);2*1H2/t20-;;/m0../s1

SMILES Code: Cc1c(C)c(C(c2ccc(Cl)cc2)=N[C@H](c3n4c(C)nn3)CC(Nc5ccc(O)cc5)=O)c4s1.O.O

Appearance: Solid powder

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

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: To be determined

Shelf Life: >2 years if stored properly

Drug Formulation: To be determined

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

HS Tariff Code: 2934.99.9001

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 528.02 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

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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.