Maritoclax

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MedKoo CAT#: 406633

CAS#: 1010732-14-5

Description: Maritoclax, also known as Marinopyrrole A , is a small molecule Mcl-1 inhibitor, which induces Mcl-1 proteasomal degradation without transcriptional downregulation. Maritoclax killed AML cell lines and primary cells with elevated Mcl-1 levels through selective Mcl-1 downregulation, and synergized with ABT-737 to overcome Mcl-1-mediated ABT-737 resistance. Maritoclax was more effective than daunorubicin at inducing leukemic cell death when co-cultured with HS-5 bone marrow stroma cells, while being less toxic than daunorubicin against HS-5 stroma cells, primary mouse bone marrow cells, and hematopoietic progenitor cells. Moreover, maritoclax administration at 20 mg/kg/d intraperitoneally caused significant U937 tumor shrinkage, as well as 36% tumors remission rate in athymic nude mice, without apparent toxicity to healthy tissue or circulating blood cells. In summary, our studies suggest that maritoclax belongs to a novel class of Mcl-1 inhibitors that has the potential to be developed for the treatment of AML. ( Cancer Biol Ther. 2014 Aug;15(8):1077-86. )


Chemical Structure

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Maritoclax
CAS# 1010732-14-5

Theoretical Analysis

MedKoo Cat#: 406633
Name: Maritoclax
CAS#: 1010732-14-5
Chemical Formula: C22H12Cl4N2O4
Exact Mass: 507.95512
Molecular Weight: 510.15
Elemental Analysis: C, 51.80; H, 2.37; Cl, 27.80; N, 5.49; O, 12.54

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Synonym: (-)-Marinopyrrole A; Marinopyrrole A; Maritoclax.

IUPAC/Chemical Name: (4,4',5,5'-tetrachloro-1'H-[1,3'-bipyrrole]-2,2'-diyl)bis((2-hydroxyphenyl)methanone)

InChi Key: QYPJBTMRYKRTFG-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H12Cl4N2O4/c23-12-9-13(19(31)10-5-1-3-7-14(10)29)28(22(12)26)18-16(24)21(25)27-17(18)20(32)11-6-2-4-8-15(11)30/h1-9,27,29-30H

SMILES Code: OC1=CC=CC=C1C(C2=C(N3C(C(C4=CC=CC=C4O)=O)=CC(Cl)=C3Cl)C(Cl)=C(Cl)N2)=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: 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

Preparing Stock Solutions

The following data is based on the product molecular weight 510.15 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

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1: Doi K, Gowda K, Liu Q, Lin JM, Sung SS, Dower C, Claxton D, Loughran TP Jr, Amin S, Wang HG. Pyoluteorin derivatives induce Mcl-1 degradation and apoptosis in hematological cancer cells. Cancer Biol Ther. 2014;15(12):1688-99. doi: 10.4161/15384047.2014.972799. PubMed PMID: 25535900.

2: Li R, Cheng C, Balasis ME, Liu Y, Garner TP, Daniel KG, Li J, Qin Y, Gavathiotis E, Sebti SM. Design, synthesis and evaluation of marinopyrrole derivatives as selective inhibitors of Mcl-1 binding to pro-apoptotic Bim and dual Mcl-1/Bcl-xL inhibitors. Eur J Med Chem. 2015 Jan 27;90:315-31. doi: 10.1016/j.ejmech.2014.11.035. Epub 2014 Nov 20. PubMed PMID: 25437618.

3: Cheng C, Liu Y, Balasis ME, Garner TP, Li J, Simmons NL, Berndt N, Song H, Pan L, Qin Y, Nicolaou KC, Gavathiotis E, Sebti SM, Li R. Marinopyrrole derivatives with sulfide spacers as selective disruptors of Mcl-1 binding to pro-apoptotic protein Bim. Mar Drugs. 2014 Jul 29;12(8):4311-25. doi: 10.3390/md12084311. PubMed PMID: 25076060; PubMed Central PMCID: PMC4145318.

4: Doi K, Liu Q, Gowda K, Barth BM, Claxton D, Amin S, Loughran TP Jr, Wang HG. Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression. Cancer Biol Ther. 2014 Aug;15(8):1077-86. doi: 10.4161/cbt.29186. Epub 2014 May 19. PubMed PMID: 24842334; PubMed Central PMCID: PMC4119075.

5: Liu Y, Haste NM, Thienphrapa W, Li J, Nizet V, Hensler M, Li R. Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (III). Mar Drugs. 2014 Apr 30;12(5):2458-70. doi: 10.3390/md12052458. PubMed PMID: 24796304; PubMed Central PMCID: PMC4052300.

6: Cheng C, Liu Y, Balasis ME, Simmons NL, Li J, Song H, Pan L, Qin Y, Nicolaou KC, Sebti SM, Li R. Cyclic marinopyrrole derivatives as disruptors of Mcl-1 and Bcl-x(L) binding to Bim. Mar Drugs. 2014 Mar 7;12(3):1335-48. doi: 10.3390/md12031335. PubMed PMID: 24608970; PubMed Central PMCID: PMC3967213.

7: Pandey MK, Gowda K, Doi K, Sharma AK, Wang HG, Amin S. Proteasomal degradation of Mcl-1 by maritoclax induces apoptosis and enhances the efficacy of ABT-737 in melanoma cells. PLoS One. 2013 Nov 4;8(11):e78570. doi: 10.1371/journal.pone.0078570. eCollection 2013. PubMed PMID: 24223823; PubMed Central PMCID: PMC3817219.

8: Eichhorn JM, Alford SE, Hughes CC, Fenical W, Chambers TC. Purported Mcl-1 inhibitor marinopyrrole A fails to show selective cytotoxicity for Mcl-1-dependent cell lines. Cell Death Dis. 2013 Oct 24;4:e880. doi: 10.1038/cddis.2013.411. PubMed PMID: 24157874; PubMed Central PMCID: PMC3920948.

9: Cheng C, Liu Y, Song H, Pan L, Li J, Qin Y, Li R. Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (II). Mar Drugs. 2013 Aug 15;11(8):2927-48. doi: 10.3390/md11082927. PubMed PMID: 23955285; PubMed Central PMCID: PMC3766874.

10: Liu Y, Haste NM, Thienphrapa W, Nizet V, Hensler M, Li R. Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (I). Mar Drugs. 2012 Apr;10(4):953-62. doi: 10.3390/md10040953. Epub 2012 Apr 24. PubMed PMID: 22690153; PubMed Central PMCID: PMC3366685.

11: Doi K, Li R, Sung SS, Wu H, Liu Y, Manieri W, Krishnegowda G, Awwad A, Dewey A, Liu X, Amin S, Cheng C, Qin Y, Schonbrunn E, Daughdrill G, Loughran TP Jr, Sebti S, Wang HG. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem. 2012 Mar 23;287(13):10224-35. doi: 10.1074/jbc.M111.334532. Epub 2012 Feb 6. PubMed PMID: 22311987; PubMed Central PMCID: PMC3323047.

12: Haste NM, Hughes CC, Tran DN, Fenical W, Jensen PR, Nizet V, Hensler ME. Pharmacological properties of the marine natural product marinopyrrole A against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2011 Jul;55(7):3305-12. doi: 10.1128/AAC.01211-10. Epub 2011 Apr 18. PubMed PMID: 21502631; PubMed Central PMCID: PMC3122406.

13: Nicolaou KC, Simmons NL, Chen JS, Haste NM, Nizet V. Total synthesis and biological evaluation of marinopyrrole A and analogues. Tetrahedron Lett. 2011 Apr 27;52(17):2041-2043. PubMed PMID: 21499535; PubMed Central PMCID: PMC3077031.

14: Kanakis AA, Sarli V. Total synthesis of (±)-marinopyrrole A via copper-mediated N-arylation. Org Lett. 2010 Nov 5;12(21):4872-5. doi: 10.1021/ol102035s. PubMed PMID: 20886840.

15: Cheng C, Pan L, Chen Y, Song H, Qin Y, Li R. Total synthesis of (+/-)-marinopyrrole A and its library as potential antibiotic and anticancer agents. J Comb Chem. 2010 Jul 12;12(4):541-7. doi: 10.1021/cc100052j. Erratum in: J Comb Chem. 2010 Nov 8;12(6):900. PubMed PMID: 20429575.

16: Hughes CC, Kauffman CA, Jensen PR, Fenical W. Structures, reactivities, and antibiotic properties of the marinopyrroles A-F. J Org Chem. 2010 May 21;75(10):3240-50. doi: 10.1021/jo1002054. PubMed PMID: 20405892; PubMed Central PMCID: PMC2884375.

17: Hughes CC, Yang YL, Liu WT, Dorrestein PC, La Clair JJ, Fenical W. Marinopyrrole A target elucidation by acyl dye transfer. J Am Chem Soc. 2009 Sep 2;131(34):12094-6. doi: 10.1021/ja903149u. PubMed PMID: 19673475; PubMed Central PMCID: PMC2769490.

18: Hughes CC, Prieto-Davo A, Jensen PR, Fenical W. The marinopyrroles, antibiotics of an unprecedented structure class from a marine Streptomyces sp. Org Lett. 2008 Feb 21;10(4):629-31. doi: 10.1021/ol702952n. Epub 2008 Jan 19. PubMed PMID: 18205372; PubMed Central PMCID: PMC2820876.



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