Calicheamicin

Calicheamicin γ1
Identifiers
CAS Number	108212-75-5 ;
3D model (JSmol)	Interactive image;
ChemSpider	27330302 ;
PubChem CID	6438329;
UNII	99ZHU54I1K ;
	InChI 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 Key: HXCHCVDVKSCDHU-LULTVBGHSA-N ; InChI=1/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 Key: HXCHCVDVKSCDHU-LULTVBGHBW;
	SMILES CCN[C@H]1CO[C@H](C[C@@H]1OC)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2O[C@H]3C#C/C=C\C#C[C@]\4(CC(=O)C(=C3/C4=C\CSSSC)NC(=O)OC)O)C)NO[C@H]5C[C@@H]([C@@H]([C@H](O5)C)SC(=O)c6c(c(c(c(c6OC)OC)O[C@H]7[C@@H]([C@@H]([C@H]([C@@H](O7)C)O)OC)O)I)C)O)O;
Properties
Chemical formula	C55H74IN3O21S4
Molar mass	1368.34 g·mol−1
Hazards
	GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H302, H341, H361, H372
Precautionary statements	P201, P202, P260, P264, P270, P281, P301+P312, P308+P313, P314, P330, P405, P501
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

The calicheamicins are a class of enediyne antitumor antibiotics derived from the bacterium Micromonospora echinospora,^[1] with calicheamicin γ1 being the most notable.^[2] It was isolated originally in the mid-1980s from the chalky soil, or "caliche pits", located in Kerrville, Texas. The sample was collected by a scientist working for Lederle Labs.^[3] 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).^[4] A second calicheamicin-linked monoclonal antibody, inotuzumab ozogamicin (marketed as Besponsa), an anti-CD22-directed antibody-drug conjugate, was approved by the U.S. Food and Drug Administration on August 17, 2017, for use in the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.^[5] Calicheamicin γ1 and the related enediyne esperamicin are the two of the most potent antitumor agents known.^[6]

^ Maiese, William M; Lechevalier, Mary P; Lechevalier, Hubert A; Korshalla, Joseph; Kuck, Nydia; Fantini, Amadeo; Wildey, Mary Jo; Thomas, John; Greenstein, Michael (April 1989). "Calicheamicins, a novel family of antitumor antibiotics: taxonomy, fermentation and biological properties". Journal of Antibiotics. 42 (4): 558–63. doi:10.7164/antibiotics.42.558. PMID 2722671.
^ Lee, May D.; Manning, Joann K.; Williams, David R.; Kuck, Nydia A.; Testa, Raymond T.; Borders, Donald B. (July 1989). "Calichemicins, a novel family of antitumor antibiotics. 3. Isolation, purification and characterization of calichemicins β1Br, γ1Br, α2I, α3I, β1I, γ1I, and Δ1I". Journal of Antibiotics. 42 (7): 1070–87. doi:10.7164/antibiotics.42.1070. PMID 2753814.
^ Total Synthesis and the Creative Process: An Interview with K.C. Nicolaou, Scripps Research Institute
^ G.A. Ellestad (2011). "Structural and Conformational Features Relevant to the Anti-Tumor Activity of Calichemicin γ1I". Chirality. 23 (8): 660–671. doi:10.1002/chir.20990. PMID 21800378.
^ "Newly Approved Drugs in ALL and NHL: How to Use Them in Practice". January 11, 2018.
^ Calicheamicin and Esperamicin are the two most potent antitumor agents known to man Archived 2008-09-21 at the Wayback Machine, Univ Of Georgia, Chem 4500

[1] Maiese, William M; Lechevalier, Mary P; Lechevalier, Hubert A; Korshalla, Joseph; Kuck, Nydia; Fantini, Amadeo; Wildey, Mary Jo; Thomas, John; Greenstein, Michael (April 1989). "Calicheamicins, a novel family of antitumor antibiotics: taxonomy, fermentation and biological properties". Journal of Antibiotics. 42 (4): 558–63. doi:10.7164/antibiotics.42.558. PMID 2722671.

[2] Lee, May D.; Manning, Joann K.; Williams, David R.; Kuck, Nydia A.; Testa, Raymond T.; Borders, Donald B. (July 1989). "Calichemicins, a novel family of antitumor antibiotics. 3. Isolation, purification and characterization of calichemicins β1Br, γ1Br, α2I, α3I, β1I, γ1I, and Δ1I". Journal of Antibiotics. 42 (7): 1070–87. doi:10.7164/antibiotics.42.1070. PMID 2753814.

[3] Total Synthesis and the Creative Process: An Interview with K.C. Nicolaou, Scripps Research Institute

[4] G.A. Ellestad (2011). "Structural and Conformational Features Relevant to the Anti-Tumor Activity of Calichemicin γ1I". Chirality. 23 (8): 660–671. doi:10.1002/chir.20990. PMID 21800378.

[5] "Newly Approved Drugs in ALL and NHL: How to Use Them in Practice". January 11, 2018.

[6] Calicheamicin and Esperamicin are the two most potent antitumor agents known to man Archived 2008-09-21 at the Wayback Machine, Univ Of Georgia, Chem 4500

[1]

[2]

[3]

[4]

[5]

[6]

Identifiers


CAS Number	108212-75-5^Y
3D model (JSmol)	Interactive image
ChemSpider	27330302^N
PubChem CID	6438329
UNII	99ZHU54I1K^N
InChI 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^N Key: HXCHCVDVKSCDHU-LULTVBGHSA-N^N InChI=1/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 Key: HXCHCVDVKSCDHU-LULTVBGHBW
SMILES CCN[C@H]1CO[C@H](C[C@@H]1OC)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2O[C@H]3C#C/C=C\C#C[C@]\4(CC(=O)C(=C3/C4=C\CSSSC)NC(=O)OC)O)C)NO[C@H]5C[C@@H]([C@@H]([C@H](O5)C)SC(=O)c6c(c(c(c(c6OC)OC)O[C@H]7[C@@H]([C@@H]([C@H]([C@@H](O7)C)O)OC)O)I)C)O)O
Properties
Chemical formula	C₅₅H₇₄IN₃O₂₁S₄
Molar mass	1368.34 g·mol⁻¹
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H302, H341, H361, H372
Precautionary statements	P201, P202, P260, P264, P270, P281, P301+P312, P308+P313, P314, P330, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is ^YN ?) Infobox references