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MedKoo Cat#: 205967 | Name: Molibresib
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Description:

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

Molibresib, also known GSK525762A, I-BET-762 and GSK525762 , is a small molecule inhibitor of the BET (Bromodomain and Extra-Terminal) family of bromodomain-containing proteins with potential antineoplastic activity. Upon administration, the BET inhibitor GSK525762 binds to the acetylated lysine recognition motifs on the bromodomain of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histone peptides. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth.

Chemical Structure

Molibresib
Molibresib
CAS#1260907-17-2 (free base)

Theoretical Analysis

MedKoo Cat#: 205967

Name: Molibresib

CAS#: 1260907-17-2 (free base)

Chemical Formula: C22H22ClN5O2

Exact Mass: 423.1462

Molecular Weight: 423.90

Elemental Analysis: C, 62.34; H, 5.23; Cl, 8.36; N, 16.52; O, 7.55

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
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Related CAS #
1895049-20-3 (besylate) 1260907-17-2 (free base)
Synonym
GSK525762; GSK525762; GSK525762; GSK525762A; GSK525762A; GSK 525762A; IBET762; IBET762; IBET 762; molibresib.
IUPAC/Chemical Name
(S)-2-(6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)-N-ethylacetamide
InChi Key
AAAQFGUYHFJNHI-SFHVURJKSA-N
InChi Code
InChI=1S/C22H22ClN5O2/c1-4-24-20(29)12-18-22-27-26-13(2)28(22)19-10-9-16(30-3)11-17(19)21(25-18)14-5-7-15(23)8-6-14/h5-11,18H,4,12H2,1-3H3,(H,24,29)/t18-/m0/s1
SMILES Code
O=C(NCC)C[C@H]1C2=NN=C(C)N2C3=CC=C(OC)C=C3C(C4=CC=C(Cl)C=C4)=N1
Appearance
Light beige 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
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).
HS Tariff Code
2934.99.9001
More Info
        
Biological target:
Molibresib (I-BET762; GSK525762) is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.
In vitro activity:
The effects of bromodomain-containing protein 4 (BRD4) inhibitor GSK525762A on the proliferation and apoptosis of primary common B-cell acute lymphoblastic leukemia (common B-ALL) cells were investigated. GSK525762A inhibited the proliferation of leukemia cells in a dose-dependent manner, the median value of IC50 was 256.25 (90.64-1 378.39)nmol/L. GSK525762A promoted cells apoptosis of B-ALL leukemia cells in a dose-dependent manner, the median apoptosis rates respectively were 45.17%(9.38%-70.91%), 66.02% (24.36%-96.34%) and 89.29% (39.29%-99.37%) after treated by 500, 1 000 and 2 500 nmol/L GSK525762A. GSK525762A had a similar effect on Ph⁺ ALL and Ph⁻ B-ALL, but the effect of proliferation inhibition and apoptosis enhancement on Ph+ B-ALL was weaker than that on Ph⁻ B-ALL. Compared with vehicle control group, the levels of c-MYC, Bcl-2 and CDK6 transcripts in leukemic cells were reduced after treatment for 24 h and 48 h by 1 000 nmol/L GSK525762A, and there were no significant differences in the downregulation of c-MYC and CDK6 mRNA between Ph⁺ and Ph⁻ B-ALL; however, the inhibitory effect on Bcl-2 transcription was weaker in Ph⁺ B-ALL cells than that in Ph⁻ B-ALL cells. Moreover, c-MYC, Bcl-2 and CDK6 protein levels decreased in GSK525762A treated group. Reference: Zhonghua Xue Ye Xue Za Zhi. 2015 Jul;36(7):563-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342640/
In vivo activity:
In Panc-1 tumor-bearing mice, GEM (Gemcitabine) and I-BET762 decreased the tumor weight and volume. The combination of GEM and I-BET762 triggered a remarkable decline in tumor weight and volume compared with that of either agent alone (Fig. 6A). TUNEL and Ki67 assays indicated that I-BET762 and GEM induced less apoptosis when used alone than did the combination treatment (Fig. 6B and C). In contrast, compared with the parental tumors, Bim-KD tumors showed noticeably weaker growth suppression in response to the combination therapy (Fig. 6A–C). Reference: Sci Rep. 2018 May 25;8(1):8102. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970200/
Solvent mg/mL mM
Solubility
DMSO 53.6 126.37
Ethanol 63.7 150.27
Water 11.0 25.95
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 423.90 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:
1. Ma S, Chen C, Zhu J, Li Y, Wang X, Song X, Cao J, Xu K. [In vitro study of BRD4 inhibitor GSK525762A against primary adult common B-cell acute lymphoblastic leukemia cells in vitro]. Zhonghua Xue Ye Xue Za Zhi. 2015 Jul;36(7):563-9. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2015.07.007. PMID: 26304078; PMCID: PMC7342640. 2. Wang X, Qi N, Ma S, Yan ZL, Wu QY, Wang L, Chen C, Xu KL. [Effect of BRD4 Inhibitor GSK525762A on Proliferation and Apoptosis of SUP-B15 Cells In Vitro and Its Possible Mechanism]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1654-1658. Chinese. doi: 10.7534/j.issn.1009-2137.2016.06.008. PMID: 28024472. 3. Xie F, Huang M, Lin X, Liu C, Liu Z, Meng F, Wang C, Huang Q. The BET inhibitor I-BET762 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine. Sci Rep. 2018 May 25;8(1):8102. doi: 10.1038/s41598-018-26496-0. PMID: 29802402; PMCID: PMC5970200.
In vitro protocol:
1. Ma S, Chen C, Zhu J, Li Y, Wang X, Song X, Cao J, Xu K. [In vitro study of BRD4 inhibitor GSK525762A against primary adult common B-cell acute lymphoblastic leukemia cells in vitro]. Zhonghua Xue Ye Xue Za Zhi. 2015 Jul;36(7):563-9. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2015.07.007. PMID: 26304078; PMCID: PMC7342640. 2. Wang X, Qi N, Ma S, Yan ZL, Wu QY, Wang L, Chen C, Xu KL. [Effect of BRD4 Inhibitor GSK525762A on Proliferation and Apoptosis of SUP-B15 Cells In Vitro and Its Possible Mechanism]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1654-1658. Chinese. doi: 10.7534/j.issn.1009-2137.2016.06.008. PMID: 28024472.
In vivo protocol:
1. Xie F, Huang M, Lin X, Liu C, Liu Z, Meng F, Wang C, Huang Q. The BET inhibitor I-BET762 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine. Sci Rep. 2018 May 25;8(1):8102. doi: 10.1038/s41598-018-26496-0. PMID: 29802402; PMCID: PMC5970200.
1: Wang M, Chen C, Xu J, Wang L, Song X, Zhang H, Zeng L, Xu K. [Effect of bromdomain protein 4 inhibitor GSK525762A on the proliferation and apoptosis of B-cell acute lymphoblastic leukemia cells and its mechanism]. Zhonghua Xue Ye Xue Za Zhi. 2014 Jun 14;35(6):528-32. doi: 10.3760/cma.j.issn.0253-2727.2014.06.012. Chinese. PubMed PMID: 24985178. 2: Parikh SA, French CA, Costello BA, Marks RS, Dronca RS, Nerby CL, Roden AC, Peddareddigari VG, Hilton J, Shapiro GI, Molina JR. NUT midline carcinoma: an aggressive intrathoracic neoplasm. J Thorac Oncol. 2013 Oct;8(10):1335-8. doi: 10.1097/JTO.0b013e3182a00f41. PubMed PMID: 24457244. 3: Chaidos A, Caputo V, Gouvedenou K, Liu B, Marigo I, Chaudhry MS, Rotolo A, Tough DF, Smithers NN, Bassil AK, Chapman TD, Harker NR, Barbash O, Tummino P, Al-Mahdi N, Haynes AC, Cutler L, Le B, Rahemtulla A, Roberts I, Kleijnen M, Witherington JJ, Parr NJ, Prinjha RK, Karadimitris A. Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762. Blood. 2014 Jan 30;123(5):697-705. doi: 10.1182/blood-2013-01-478420. Epub 2013 Dec 13. PubMed PMID: 24335499. 4: Dawson MA, Gudgin EJ, Horton SJ, Giotopoulos G, Meduri E, Robson S, Cannizzaro E, Osaki H, Wiese M, Putwain S, Fong CY, Grove C, Craig J, Dittmann A, Lugo D, Jeffrey P, Drewes G, Lee K, Bullinger L, Prinjha RK, Kouzarides T, Vassiliou GS, Huntly BJ. Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia. Leukemia. 2014 Feb;28(2):311-20. doi: 10.1038/leu.2013.338. Epub 2013 Nov 13. PubMed PMID: 24220271; PubMed Central PMCID: PMC3918873. 5: Zhao Y, Yang CY, Wang S. The making of I-BET762, a BET bromodomain inhibitor now in clinical development. J Med Chem. 2013 Oct 10;56(19):7498-500. doi: 10.1021/jm4014407. Epub 2013 Sep 25. PubMed PMID: 24107192. 6: Mirguet O, Gosmini R, Toum J, Clément CA, Barnathan M, Brusq JM, Mordaunt JE, Grimes RM, Crowe M, Pineau O, Ajakane M, Daugan A, Jeffrey P, Cutler L, Haynes AC, Smithers NN, Chung CW, Bamborough P, Uings IJ, Lewis A, Witherington J, Parr N, Prinjha RK, Nicodème E. Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains. J Med Chem. 2013 Oct 10;56(19):7501-15. doi: 10.1021/jm401088k. Epub 2013 Sep 25. PubMed PMID: 24015967. 7: Wyce A, Ganji G, Smitheman KN, Chung CW, Korenchuk S, Bai Y, Barbash O, Le B, Craggs PD, McCabe MT, Kennedy-Wilson KM, Sanchez LV, Gosmini RL, Parr N, McHugh CF, Dhanak D, Prinjha RK, Auger KR, Tummino PJ. BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models. PLoS One. 2013 Aug 23;8(8):e72967. doi: 10.1371/journal.pone.0072967. eCollection 2013. PubMed PMID: 24009722; PubMed Central PMCID: PMC3751846. 8: Boehm D, Calvanese V, Dar RD, Xing S, Schroeder S, Martins L, Aull K, Li PC, Planelles V, Bradner JE, Zhou MM, Siliciano RF, Weinberger L, Verdin E, Ott M. BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism. Cell Cycle. 2013 Feb 1;12(3):452-62. doi: 10.4161/cc.23309. Epub 2012 Feb 1. PubMed PMID: 23255218; PubMed Central PMCID: PMC3587446. 9: Bandukwala HS, Gagnon J, Togher S, Greenbaum JA, Lamperti ED, Parr NJ, Molesworth AM, Smithers N, Lee K, Witherington J, Tough DF, Prinjha RK, Peters B, Rao A. Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14532-7. doi: 10.1073/pnas.1212264109. Epub 2012 Aug 21. PubMed PMID: 22912406; PubMed Central PMCID: PMC3437860. 10: Maxmen A. Cancer research: Open ambition. Nature. 2012 Aug 9;488(7410):148-50. doi: 10.1038/488148a. PubMed PMID: 22874946. 11: Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J, Chesi M, Schinzel AC, McKeown MR, Heffernan TP, Vakoc CR, Bergsagel PL, Ghobrial IM, Richardson PG, Young RA, Hahn WC, Anderson KC, Kung AL, Bradner JE, Mitsiades CS. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17. doi: 10.1016/j.cell.2011.08.017. Epub 2011 Sep 1. PubMed PMID: 21889194; PubMed Central PMCID: PMC3187920. 12: Oliver SS, Denu JM. Disrupting the reader of histone language. Angew Chem Int Ed Engl. 2011 Jun 20;50(26):5801-3. doi: 10.1002/anie.201101414. Epub 2011 May 25. PubMed PMID: 21618372; PubMed Central PMCID: PMC3327163. 13: Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK, Lee K, Tarakhovsky A. Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468(7327):1119-23. doi: 10.1038/nature09589. Epub 2010 Nov 10. PubMed PMID: 21068722.