Calicheamicin

Calicheamicin, an antitumor antibiotic, is a cytotoxic agent that causes double-strand DNA breaks. Calicheamicin is a DNA synthesis inhibitor.

Product information

CAS Number: 108212-75-5

Molecular Weight: 1368.35

Formula: C55H74IN3O21S4

Synonym:

Calicheamicin γ1

Chemical Name: methyl N-[(1R, 8S, 13Z)-8-{[(2R, 3R, 4S, 5S, 6R)-5-({[(2S, 4S, 5S, 6R)-5-(4-{[(2S, 3R, 4R, 5S, 6S)-3, 5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-3-iodo-5, 6-dimethoxy-2-methylbenzoylsulfanyl)-4-hydroxy-6-methyloxan-2-yl]oxy}amino)-3-{[(2S, 4S, 5S)-5-(ethylamino)-4-methoxyoxan-2-yl]oxy}-4-hydroxy-6-methyloxan-2-yl]oxy}-1-hydroxy-13-{2-[(methylsulfanyl)disulfanyl]ethylidene}-11-oxobicyclo[7.3.1]trideca-4, 9-dien-2, 6-diyn-10-yl]carbamate

Smiles: CC1C(I)=C(O[C@@H]2O[C@@H](C)[C@H](O)[C@@H](OC)[C@H]2O)C(OC)=C(OC)C=1C(=O)S[C@H]1[C@@H](O)C[C@H](ON[C@H]2[C@H](O)[C@@H](O[C@H]3C[C@H](OC)[C@H](CO3)NCC)[C@H](O[C@H]3C#CC=CC#C[C@]4(O)CC(=O)C(NC(=O)OC)=C3/C/4=C/CSSSC)O[C@@H]2C)O[C@@H]1C |c:58|

InChiKey: HXCHCVDVKSCDHU-GPCZLZLMSA-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

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : ≥ 100 mg/mL (73.08 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

PF-06647263 (anti-EFNA4-ADC) is generated via conjugation of hE22 lysine residues to the AcButDMH-N-Ac-calicheamicin-γ1 linker-payload with an average drug-to-antibody ratio (DAR) of 4.6. PF-06647263 elicits antigen- and concentration-dependent cytotoxicity, as exposure to PF-06647263 for 96 hours results in cell death (EC50= appr 1 ng/mL). CMC-544, consisting of a humanized CD22 Ab linked to calicheamicin, is effective in pediatric primary B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells in vitro. CMC-544 induces cell death in various ALL cell lines in a dose- and time-dependent way, with IC50 values ranging from 0.15 to 4.9 ng/mL. CMC-544 (10 ng/mL) is effective and specific in primary BCP-ALL cells. In CMC-544-treated cells, the level of CD22 has decreased relative to that on G5/44-treated cells and continued to decrease.

In Vivo:

An ADC comprising a humanized anti-EFNA4 monoclonal antibody conjugated to the DNA-damaging agent calicheamicin achieves sustained tumor regressions in both TNBC and ovarian cancer PDX in vivo. PF-06647263 (0.27, 0.36 mg/kg) results in significant tumor regressions in TNBC xenografts.

References:

1. Damelin M, et al. 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
2. Takeshita A, et al. CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, alters the levels of target molecules of malignant B-cells. Leukemia. 2009 Jul;23(7):1329-36.

Products are for research use only. Not for human use.