Calicheamicin

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

MedKoo CAT#: 319914

CAS#: 108212-75-5

Description: Calicheamicin, also known as Calicheamicin gamma(1,I) or Calichemicin gamma1, is an potent enediyne antitumor antibiotics derived from the bacterium Micromonospora echinospora. Calicheamicin targets DNA and cause strand scission. Calicheamicin binds with DNA in the minor groove, wherein it then undergos a reaction analogous to the Bergman cyclization to generate a diradical species. This diradical, 1,4-didehydrobenzene, then abstracts hydrogen atoms from the deoxyribose (sugar) backbone of DNA, which ultimately leads to strand scission. The specificity of binding of calicheamicin to the minor groove of DNA is due to the aryltetrasaccharide group of the molecule.


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Calicheamicin is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 319914
Name: Calicheamicin
CAS#: 108212-75-5
Chemical Formula: C55H74IN3O21S4
Exact Mass: 1367.2742
Molecular Weight: 1368.3415
Elemental Analysis: C, 48.28; H, 5.45; I, 9.27; N, 3.07; O, 24.55; S, 9.37


Synonym: Calicheamicin; Calicheamicin gamma(1,I); Calichemicin gamma1; Calicheamicin gamma(1)I.

IUPAC/Chemical Name: S-((2R,3S,4S,6S)-6-((((2R,3S,4S,5R)-5-(((2S,4S,5S)-5-(ethylamino)-4-methoxytetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(((2S,5Z,9S,13E)-9-hydroxy-12-((methoxycarbonyl)amino)-13-(2-(methyltrisulfanyl)ethylidene)-11-oxobicyclo[7.3.1]trideca-1(12),5-dien-3,7-diyn-2-yl)oxy)-2-methyltetrahydro-2H-pyran-3-yl)amino)oxy)-4-hydroxy-2-methyltetrahydro-2H-pyran-3-yl) 4-(((2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-3-iodo-5,6-dimethoxy-2-methylbenzothioate

InChi Key: HXCHCVDVKSCDHU-IXTZGUNISA-N

InChi Code: InChI=1S/C55H74IN3O21S4/c1-12-57-30-24-73-35(22-34(30)68-6)78-48-43(63)40(26(3)75-53(48)77-33-17-15-13-14-16-19-55(67)23-32(61)41(58-54(66)72-10)38(33)29(55)18-20-82-84-81-11)59-80-36-21-31(60)50(28(5)74-36)83-51(65)37-25(2)39(56)46(49(71-9)45(37)69-7)79-52-44(64)47(70-8)42(62)27(4)76-52/h13-14,18,26-28,30-31,33-36,40,42-44,47-48,50,52-53,57,59-60,62-64,67H,12,20-24H2,1-11H3,(H,58,66)/b14-13-,29-18+/t26-,27+,28-,30+,31+,33+,34+,35+,36+,40-,42+,43+,44-,47-,48-,50-,52+,53?,55-/m1/s1

SMILES Code: O=C(S[C@@H]1[C@@H](C)O[C@@H](ON[C@@H]2[C@@H](C)OC(O[C@@H](C#C/C=C\C#C[C@@]3(O)C4)C(/C3=C\CSSSC)=C(NC(OC)=O)C4=O)[C@H](O[C@H]5C[C@H](OC)[C@@H](NCC)CO5)[C@H]2O)C[C@@H]1O)C6=C(OC)C(OC)=C(O[C@H]7[C@H](O)[C@H](OC)[C@@H](O)[C@H](C)O7)C(I)=C6C


Technical Data

Appearance:
Solid powder

Purity:
>95% (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).

Harmonized System Code:
293490


Additional Information

The calicheamicins are a class of enediyne antitumor antibiotics derived from the bacterium Micromonospora echinospora, with calicheamicin γ1 being the most notable. It was isolated originally in the mid-1980s from the chalky soil, or "calichi pits", located in Kerrville, Texas. The sample was collected by a scientist working for Lederle Labs. It is extremely toxic to all cells and, in 2000, a CD33 antigen-targeted immunoconjugate N-acetyl dimethyl hydrazide calicheamicin was developed and marketed as targeted therapy against the non-solid tumor cancer acute myeloid leukemia (AML). Calicheamicin γ1 and the related enediyne esperamicin are the two of the most potent antitumor agents known.


References

1: Singh S, Michalska K, Bigelow L, Endres M, Kharel MK, Babnigg G, Yennamalli RM, Bingman CA, Joachimiak A, Thorson JS, Phillips GN Jr. Structural Characterization of CalS8, a TDP-α-D-Glucose Dehydrogenase Involved in Calicheamicin Aminodideoxypentose Biosynthesis. J Biol Chem. 2015 Oct 23;290(43):26249-58. doi: 10.1074/jbc.M115.673459. Epub 2015 Aug 3. PubMed PMID: 26240141; PubMed Central PMCID: PMC4646273.

2: Tsodikov OV, Hou C, Walsh CT, Garneau-Tsodikova S. Crystal structure of O-methyltransferase CalO6 from the calicheamicin biosynthetic pathway: a case of challenging structure determination at low resolution. BMC Struct Biol. 2015 Jul 15;15:13. doi: 10.1186/s12900-015-0040-6. PubMed PMID: 26170207; PubMed Central PMCID: PMC4501126.

3: Damelin M, Bankovich A, Park A, Aguilar J, Anderson W, Santaguida M, Aujay M, Fong S, Khandke K, Pulito V, Ernstoff E, Escarpe P, Bernstein J, Pysz M, Zhong W, Upeslacis E, Lucas J, Lucas J, Nichols T, Loving K, Foord O, Hampl J, Stull R, Barletta F, Falahatpisheh H, Sapra P, Gerber HP, Dylla SJ. Anti-EFNA4 Calicheamicin Conjugates Effectively Target Triple-Negative Breast and Ovarian Tumor-Initiating Cells to Result in Sustained Tumor Regressions. Clin Cancer Res. 2015 Sep 15;21(18):4165-73. doi: 10.1158/1078-0432.CCR-15-0695. Epub 2015 May 26. PubMed PMID: 26015513.

4: Sissi C, Moro S, Crothers DM. Novel insights on the DNA interaction of calicheamicin γ₁(I). Biopolymers. 2015 Aug;103(8):449-59. doi: 10.1002/bip.22591. PubMed PMID: 25411012.

5: Song H, Xu R, Guo Z. Identification and characterization of a methionine γ-lyase in the calicheamicin biosynthetic cluster of Micromonospora echinospora. Chembiochem. 2015 Jan 2;16(1):100-9. doi: 10.1002/cbic.201402489. Epub 2014 Nov 17. PubMed PMID: 25404066.

6: Singh S, Nandurkar NS, Thorson JS. Characterization of the calicheamicin orsellinate C2-O-methyltransferase CalO6. Chembiochem. 2014 Jul 7;15(10):1418-21. doi: 10.1002/cbic.201402119. PubMed PMID: 24978950; PubMed Central PMCID: PMC4111469.

7: Singh S, Chang A, Helmich KE, Bingman CA, Wrobel RL, Beebe ET, Makino S, Aceti DJ, Dyer K, Hura GL, Sunkara M, Morris AJ, Phillips GN Jr, Thorson JS. Structural and functional characterization of CalS11, a TDP-rhamnose 3'-O-methyltransferase involved in calicheamicin biosynthesis. ACS Chem Biol. 2013 Jul 19;8(7):1632-9. doi: 10.1021/cb400068k. Epub 2013 May 23. PubMed PMID: 23662776; PubMed Central PMCID: PMC3875630.

8: Belecki K, Townsend CA. Environmental control of the calicheamicin polyketide synthase leads to detection of a programmed octaketide and a proposal for enediyne biosynthesis. Angew Chem Int Ed Engl. 2012 Nov 5;51(45):11316-9. doi: 10.1002/anie.201206462. Epub 2012 Oct 8. PubMed PMID: 23042574; PubMed Central PMCID: PMC3487408.

9: Nicolaou KC, Hale CR, Nilewski C. A total synthesis trilogy: calicheamicin γ1(I), Taxol®, and brevetoxin A. Chem Rec. 2012 Aug;12(4):407-41. doi: 10.1002/tcr.201200005. Epub 2012 Jun 18. Review. PubMed PMID: 22711588.

10: Ricart AD. Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin Cancer Res. 2011 Oct 15;17(20):6417-27. doi: 10.1158/1078-0432.CCR-11-0486. Review. PubMed PMID: 22003069.

11: Chang A, Singh S, Helmich KE, Goff RD, Bingman CA, Thorson JS, Phillips GN Jr. Complete set of glycosyltransferase structures in the calicheamicin biosynthetic pathway reveals the origin of regiospecificity. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17649-54. doi: 10.1073/pnas.1108484108. Epub 2011 Oct 10. PubMed PMID: 21987796; PubMed Central PMCID: PMC3203770.

12: de Vries JF, Zwaan CM, De Bie M, Voerman JS, den Boer ML, van Dongen JJ, van der Velden VH. The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells. Leukemia. 2012 Feb;26(2):255-64. doi: 10.1038/leu.2011.206. Epub 2011 Aug 26. PubMed PMID: 21869836.

13: Ellestad GA. Structural and conformational features relevant to the anti-tumor activity of calicheamicin γ 1I. Chirality. 2011 Sep;23(8):660-71. doi: 10.1002/chir.20990. Epub 2011 Jul 28. Review. PubMed PMID: 21800378.

14: Goff RD, Singh S, Thorson JS. Glycosyloxyamine neoglycosylation: a model study using calicheamicin. ChemMedChem. 2011 May 2;6(5):774-6. doi: 10.1002/cmdc.201100028. Epub 2011 Feb 23. PubMed PMID: 21520418; PubMed Central PMCID: PMC3081727.

15: Chang A, Singh S, Bingman CA, Thorson JS, Phillips GN Jr. Structural characterization of CalO1: a putative orsellinic acid methyltransferase in the calicheamicin-biosynthetic pathway. Acta Crystallogr D Biol Crystallogr. 2011 Mar;67(Pt 3):197-203. doi: 10.1107/S090744491100360X. Epub 2011 Feb 15. PubMed PMID: 21358050; PubMed Central PMCID: PMC3046457.

16: Maeda E, Urakami K, Shimura K, Kinoshita M, Kakehi K. Charge heterogeneity of a therapeutic monoclonal antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin. J Chromatogr A. 2010 Nov 5;1217(45):7164-71. doi: 10.1016/j.chroma.2010.09.022. Epub 2010 Sep 17. PubMed PMID: 20932526.

17: DiJoseph JF, Dougher MM, Evans DY, Zhou BB, Damle NK. Preclinical anti-tumor activity of antibody-targeted chemotherapy with CMC-544 (inotuzumab ozogamicin), a CD22-specific immunoconjugate of calicheamicin, compared with non-targeted combination chemotherapy with CVP or CHOP. Cancer Chemother Pharmacol. 2011 Apr;67(4):741-9. doi: 10.1007/s00280-010-1342-9. Epub 2010 Jun 3. PubMed PMID: 20521053.

18: Cianfriglia M, Mallano A, Ascione A, Dupuis ML. Multidrug transporter proteins and cellular factors involved in free and mAb linked calicheamicin-gamma1 (gentuzumab ozogamicin, GO) resistance and in the selection of GO resistant variants of the HL60 AML cell line. Int J Oncol. 2010 Jun;36(6):1513-20. PubMed PMID: 20428776.

19: Usuki T, Kawai M, Nakanishi K, Ellestad GA. Calicheamicin γ1(I) and phenyl tert-butyl nitrone (PBN): observation of a kinetic isotope effect by an ESR study. Chem Commun (Camb). 2010 Feb 7;46(5):737-9. doi: 10.1039/b913414j. Epub 2009 Nov 25. PubMed PMID: 20087504.

20: Belecki K, Crawford JM, Townsend CA. Production of octaketide polyenes by the calicheamicin polyketide synthase CalE8: implications for the biosynthesis of enediyne core structures. J Am Chem Soc. 2009 Sep 9;131(35):12564-6. doi: 10.1021/ja904391r. PubMed PMID: 19689130; PubMed Central PMCID: PMC2760317.