Name: Calicheamicin
Brand: BOC Sciences
Price: 376 USD
Availability: MadeToOrder

Synonyms

calicheamicin γ1

IUPAC Name

S-[(2R,3S,4S,6S)-6-[[(2R,3S,4S,5R,6R)-5-[(2S,4S,5S)-5-(ethylamino)-4-methoxyoxan-2-yl]oxy-4-hydroxy-6-[[(2S,5Z,9R,13Z)-9-hydroxy-12-(methoxycarbonylamino)-13-[2-(methyltrisulfanyl)ethylidene]-11-oxo-2-bicyclo[7.3.1]trideca-1(12),5-dien-3,7-diynyl]oxy]-2-methyloxan-3-yl]amino]oxy-4-hydroxy-2-methyloxan-3-yl] 4-[(2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5-iodo-2,3-dimethoxy-6-methylbenzenecarbothioate

Canonical SMILES

CCNC1COC(CC1OC)OC2C(C(C(OC2OC3C#CC=CC#CC4(CC(=O)C(=C3C4=CCSSSC)NC(=O)OC)O)C)NOC5CC(C(C(O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)OC7C(C(C(C(O7)C)O)OC)O)I)C)O)O

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

InChIKey

HXCHCVDVKSCDHU-GPCZLZLMSA-N

Density

1.6±0.1 g/cm3

Solubility

Soluble in DMSO, not in water

Index Of Refraction

1.662

PSA

409.64000

Appearance

White solid powder

Shelf Life

2 years if stored properly

Shipping

Room temperature

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

Pictograms

Irritant; Health Hazard

Signal Word

Danger

In Vitro

The animal metabolism of nemorubicin (MMDX) proved to be qualitatively similar to that observed with HLMs since, in all tested species, MMDX was mainly converted to PNU-159682 by a single CYP3A form. However, there were marked quantitative inter- and intra-species differences in kinetic parameters. The mouse and the male rat exhibited V(max) and intrinsic metabolic clearance (CL(int)) values closest to those of human beings, suggesting that these species are the most suitable animal models to investigate MMDX biotransformation. A close inverse correlation was found between MMDX CL(int) and previously reported values of MMDX LD(50) for animals of the species, sex and strain tested here, indicating that differences in the in vivo toxicity of MMDX are most probably due to sex- and species-related differences in the extent of PNU-159682 formation.

In Vivo

Homogeneous conjugate calicheamicin possess minimal aggregation and display high in vivo stability with 50% of the drug remaining conjugated to the antibody after 21 days. Furthermore, this calicheamicin ADCs are highly efficacious in mouse models of both solid tumor (HER2+ breast cancer) and hematologic malignancies (CD22+ non-Hodgkin lymphoma). Safety studies in rats with this novel calicheamicin ADC revealed an increased tolerability compared with that reported for Mylotarg.

Calicheamicin is a potent enediyne antibiotic and a highly cytotoxic ADC payload widely used in antibody-drug conjugates for targeted cancer therapy. Its cytotoxic mechanism involves sequence-specific binding to the minor groove of DNA, followed by oxidative DNA strand cleavage through enediyne-mediated activation. This leads to DNA double-strand breaks, cell cycle arrest, and induction of apoptosis in proliferating tumor cells. Calicheamicin’s structure allows covalent conjugation to monoclonal antibodies via cleavable or non-cleavable linkers, enabling precise intracellular delivery in ADC applications while maintaining systemic stability.

Within antibody-drug conjugates, Calicheamicin is attached to antibodies using linker chemistries optimized for plasma stability and controlled intracellular release. The ADC remains inactive in circulation, minimizing off-target cytotoxicity. Upon receptor-mediated internalization into antigen-expressing tumor cells, enzymatic or chemical cleavage of the linker liberates the active Calicheamicin payload. Once released, it binds to the DNA minor groove and induces DNA strand cleavage, leading to apoptosis. This targeted mechanism ensures that cytotoxic effects are confined to tumor cells, supporting precise tumor-targeted therapy in ADC constructs.

Applications of Calicheamicin include incorporation into ADCs targeting hematologic malignancies and solid tumors with specific antigen expression. Its chemical compatibility with diverse linker systems allows optimization of conjugation efficiency, intracellular release kinetics, and pharmacokinetic profiles. Preclinical and clinical studies demonstrate potent cytotoxicity in antigen-expressing tumor cells. Calicheamicin supports the development of ADCs with defined DNA-damaging mechanisms, providing mechanistically precise induction of apoptosis and tumor cell elimination, facilitating rational design and evaluation of antibody-drug conjugates in oncology applications.

1. The cure of leukemia through the optimist's prism

Hagop M Kantarjian, Nitin Jain, Guillermo Garcia-Manero, Mary Alma Welch, Farhad Ravandi, William G Wierda, Elias J Jabbour Cancer. 2022 Jan 15;128(2):240-259. doi: 10.1002/cncr.33933. Epub 2021 Oct 6.

Progress is occurring at a dizzying rate across all leukemias. Since the authors' review of the topic in Cancer in 2018, numerous discoveries have been made that have improved the therapy and outcomes of several leukemia subsets. Hairy cell leukemia is potentially curable with a single course of cladribine followed by rituximab (10-year survival, ≥90%). Acute promyelocytic leukemia is curable at a rate of 80% to 90% with a nonchemotherapy regimen of all-trans retinoic acid and arsenic trioxide. The cure rate for core-binding factor acute myeloid leukemia (AML) is ≥75% with fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin. Survival for patients with chronic myeloid leukemia is close to that for an age-matched normal population with BCR-ABL1 tyrosine kinase inhibitors (TKIs). Chronic lymphocytic leukemia, a previously incurable disease, may now be potentially curable with a finite duration of therapy with Bruton tyrosine kinase inhibitors and venetoclax. The estimated 5-year survival rate for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) exceeds 70% with intensive chemotherapy and ponatinib, a third-generation BCR-ABL1 TKI, and more recent nonchemotherapy regimens using dasatinib or ponatinib with blinatumomab are producing outstanding results. Survival in both younger and older patients with ALL has improved with the addition of antibodies targeting CD20, CD19 (blinatumomab), and CD22 (inotuzumab) to chemotherapy. Several recent drug discoveries (venetoclax, FLT3 and IDH inhibitors, and oral hypomethylating agents) are also improving outcomes for younger and older patients with AML and for those with higher risk myelodysplastic syndrome.

2. ABBV-011, A Novel, Calicheamicin-Based Antibody-Drug Conjugate, Targets SEZ6 to Eradicate Small Cell Lung Cancer Tumors

Wolf R Wiedemeyer, Julia Gavrilyuk, Alexander Schammel, Xi Zhao, Hetal Sarvaiya, Marybeth Pysz, Christine Gu, Monica You, Kumiko Isse, Theodore Sullivan, Dorothy French, Christina Lee, Angeline T Dang, Zhaomei Zhang, Monette Aujay, Alexander J Bankovich, Philip Vitorino Mol Cancer Ther. 2022 Jun 1;21(6):986-998. doi: 10.1158/1535-7163.MCT-21-0851.

In the past year, four antibody-drug conjugates (ADC) were approved, nearly doubling the marketed ADCs in oncology. Among other attributes, successful ADCs optimize targeting antibody, conjugation chemistry, and payload mechanism of action. Here, we describe the development of ABBV-011, a novel SEZ6-targeted, calicheamicin-based ADC for the treatment of small cell lung cancer (SCLC). We engineered a calicheamicin conjugate that lacks the acid-labile hydrazine linker that leads to systemic release of a toxic catabolite. We then screened a patient-derived xenograft library to identify SCLC as a tumor type with enhanced sensitivity to calicheamicin ADCs. Using RNA sequencing (RNA-seq) data from primary and xenograft SCLC samples, we identified seizure-related homolog 6 (SEZ6) as a surface-expressed SCLC target with broad expression in SCLC and minimal normal tissue expression by both RNA-seq and IHC. We developed an antibody targeting SEZ6 that is rapidly internalized upon receptor binding and, when conjugated to the calicheamicin linker drug, drives potent tumor regression in vitro and in vivo. These preclinical data suggest that ABBV-011 may provide a novel treatment for patients with SCLC and a rationale for ongoing phase I studies (NCT03639194).

3. Targeted inhibitors and antibody immunotherapies: Novel therapies for paediatric leukaemia and lymphoma

Erica Brivio, André Baruchel, Auke Beishuizen, Jean-Pierre Bourquin, Patrick A Brown, Todd Cooper, Lia Gore, E Anders Kolb, Franco Locatelli, Shannon L Maude, Francis J Mussai, Britta Vormoor-Bürger, Josef Vormoor, Arend von Stackelberg, C Michel Zwaan Eur J Cancer. 2022 Mar;164:1-17. doi: 10.1016/j.ejca.2021.12.029. Epub 2022 Feb 1.

Despite improved outcomes achieved in the last decades for children with newly diagnosed leukaemia and lymphoma, treatment of patients with refractory/relapsed disease remains a challenge. The cure rate is still unsatisfactory and often achieved at the cost of significant morbidity. Exploring treatment with novel agents should offer less toxic therapeutic options, without compromising efficacy. Bispecific and antibody-drug conjugates targeting CD19 and CD22 (blinatumomab and inotuzumab ozogamicin) play an important role in the treatment of relapsed and refractory B-cell precursor acute lymphoblastic leukaemia (BCP-ALL); antibodies targeting CD123 and CD38 are also under investigation for acute myeloid leukaemia (AML) and T-ALL, respectively. Targeted therapy with small molecules is of primary importance for specific genetic subtypes, such as BCR-ABL-positive ALL, FLT3-ITD AML and anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. KMT2A-directed targeted therapy with menin inhibitors holds promise to be of relevance in KMT2A-rearranged leukaemias, known to have dismal prognosis. Target inhibition in cellular pathways such as BCL-2, RAS, MEK, Bruton's tyrosine kinase, JAK-STAT or CDK4/CDK6 inhibition may be suitable for different diseases with common mutated pathways. Nevertheless, development and approval of new agents for paediatric cancers lags behind adult therapeutic options. New regulations were implemented to accelerate drug development for children. Considering the number of oncology medicinal products available for adults and the rarity of paediatric cancers, prioritisation based on scientific evidence and medical need, as well as international collaboration, is critical. Herein, we review the current status of drug development for children with leukaemia and lymphoma, excluding cellular therapy despite its well-known significance.

Catalog	Product Name	CAS	Inquiry
BADC-00723	N-Acetyl-Calicheamicin	108212-76-6

What is Calicheamicin?

Calicheamicin is a potent enediyne antitumor antibiotic used as a cytotoxic payload in ADCs. It binds to the DNA minor groove and induces double-strand breaks, leading to rapid apoptosis of targeted cells.

24/8/2019

Could you explain how Calicheamicin is applied in ADCs?

Calicheamicin is conjugated to antibodies via cleavable or non-cleavable linkers to selectively deliver cytotoxic effects to antigen-expressing tumor cells, enhancing ADC efficacy while limiting systemic toxicity.

12/3/2017

We would like to know which linkers are suitable for Calicheamicin.

Calicheamicin is compatible with disulfide and other cleavable linkers, allowing controlled drug release in target cells. Non-cleavable linkers can also be used depending on desired pharmacokinetics and stability.

22/12/2018

Good morning! Could you let me know if BOC Sciences can provide Calicheamicin ADC services?

BOC Sciences offers Calicheamicin ADC development services including payload conjugation, linker optimization, and analytical characterization, enabling tailored ADC constructs for preclinical research.

15/8/2017

Good morning! What safety measures should be followed when handling Calicheamicin?

Calicheamicin is extremely cytotoxic and requires stringent handling protocols, including use of PPE, biosafety cabinets, and strict laboratory procedures to ensure safe manipulation during research.

4/12/2020

— Dr. Peter Hall, Senior Scientist (USA)

Calicheamicin delivered by BOC Sciences exhibited exceptional purity, supporting precise conjugation protocols.

22/12/2018

— Dr. Richard Miller, Oncology Researcher (USA)

Calicheamicin provided by BOC Sciences was of outstanding quality, enabling precise and reproducible conjugation studies.

4/12/2020

— Ms. Julia Schneider, Senior Scientist (Germany)

Fast and reliable supply of Calicheamicin with complete analytical data allowed us to accelerate our ADC research.

15/8/2017

— Dr. Andrew Clarke, Project Lead (UK)

Consistency in Calicheamicin batches has been key to successful linker-payload development in our projects.