Duocarmycin A
Duocarmycin A is an antitumor antibiotic and DNA alkylating agent with broad-spectrum antibacterial activity, which can serve as a payload for synthesizing antibody-drug conjugates (ADCs). Duocarmycin A selectively binds to the AT-rich minor groove of DNA, forms covalent adducts by alkylating the adenine N3 residue, thereby disrupting DNA structure and inhibiting its replication and transcription. Duocarmycin A induces apoptosis, sub-G1 phase accumulation and chromatin condensation, reduces the levels of pro-caspase-3/9, and induces p53-independent p21 expression. Duocarmycin A is widely used in the research of various malignancies, including leukemia, sarcoma, glioblastoma, as well as multiple solid tumor models such as lung cancer, breast cancer, and colorectal cancer.
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- CAS No.: 118292-34-5
- Formule: C26H25N3O8
- Masse moléculaire:507.49
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
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Procaspase-3 |
Caspase-9 |
Duocarmycins |
Duocarmycin A (0.0016-0.0064 μg/ml; 0.032-42 μg/ml) potently inhibits the growth of Gram-positive bacterial strains (MIC 0.0016-0.0064 μg/ml) and exhibits variable inhibitory activity against Gram-negative bacterial and fungal strains (MIC 0.032-42 μg/ml)[1].
Duocarmycin A (0.003-0.03 μg/mL) induces intrinsic pathway apoptosis and G1 phase cell cycle arrest in HLC-2 cells in vitro in a dose-dependent manner, with altered expression of key apoptotic proteins (caspase-3, caspase-9, Bax) at 0.03 μg/mL[2].
Duocarmycin A (0.003-0.03 μg/ml; 72 h) induces concentration-dependent apoptosis in HLC-2 cells, with 27% apoptosis at 0.003 μg/ml and 51% apoptosis at 0.03 μg/ml after 72 h of treatment, accompanied by characteristic apoptotic nuclear morphology[3].
Duocarmycin A (0.003-0.03 μg/ml; 24-72 h) induces time- and concentration-dependent accumulation of apoptotic sub-G1 phase cells in HLC-2 cultures, with higher sub-G1 populations observed at 0.03 μg/ml compared to 0.003 μg/ml across 24, 48, and 72 h treatments[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human acute myeloid leukemia HL-60 (H2O2-sensitive) and HP100 (H2O2-resistant) cells
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Concentration:10 nM
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Incubation Time:30 min, 1 h, 2 h, 3 h, 4 h
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Result:Induced DNA fragments in both cell lines at 30 min. Triggered DNA ladder formation at 2 h in HL-60 cells and at 3-4 h in HP100 cells.
Reached maximal caspase-3 activity at 3 h in HL-60 cells and 4 h in HP100 cells; did not induce detectable caspase-1 activity in either cell line.
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Cell Line:human lung carcinoma (HLC-2) cells
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Concentration:0.003 μg/ml; 0.03 μg/ml
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Incubation Time:24 h; 48 h; 72 h
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Result:Resulted in sub-G1 phase (apoptotic) cell populations of 3.94% at 24 h, 12.37% at 48 h, and 6.86% at 72 h at 0.003 μg/ml. Resulted in sub-G1 phase cell populations of 5.56% at 24 h, 15.26% at 48 h, and 20.72% at 72 h at 0.03 μg/ml.
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Cell Line:human lung carcinoma (HLC-2) cells
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Concentration:0.003 μg/ml; 0.03 μg/ml
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Incubation Time:72 h (procaspase-3, procaspase-9, procaspase-8, Bax, Bcl-2); 24, 48, 72 h (p53, p21)
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Result:Decreased levels of the 32-kDa procaspase-3 and 47-kDa procaspase-9 precursors, and increased levels of pro-apoptotic Bcl-2 family protein Bax after 72 h of treatment; showed no change in procaspase-8 or Bcl-2 levels. Induced relatively high expression of p21, with extremely low accumulation of p53 across 24, 48, and 72 h of treatment.
Duocarmycin-based B2M-ADC selectively targets senescent cancer cells and reduces their viability in in vivo models, with its activity exhibiting senescence phenotype specificity[2].
Galactose-modified Duocarmycin can selectively induce cell death in senescent cancer cells in mice by targeting SA-β-gal activity[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ddY mice with Murine sarcoma 180[1]
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Dosage:0.04 mg/kg (i.p.);
0.03 mg/kg (i.v.);
0.015 mg/kg (i.v.);
0.0075 mg/kg (i.v.) -
Administration:i.p. or i.v.; single dose
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Result:Achieved a T/C ratio of 0.35 at 0.04 mg/kg i.p. single dose.\nExhibited T/C ratios ranging from 0.26 to 0.42 at 0.03-0.0075 mg/kg i.v. single doses.
Chemical Information
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CAS No. 118292-34-5
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Masse moléculaire 507.49
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Formule C26H25N3O8
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SMILES
O=C([C@@](N1)(C)C(C([C@@]23[C@@](C3)([H])CN(C(C(N4)=CC5=C4C(OC)=C(OC)C(OC)=C5)=O)C2=C6)=C1C6=O)=O)OC
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[2]. Morcos A, et al. A Comprehensive Review of the Antitumor Properties and Mechanistic Insights of Duocarmycin Analogs. Cancers (Basel). 2024;16(19):3293. Published 2024 Sep 27. [Content Brief]
[3]. Hirota M, et al. Distamycin A enhances the cytotoxicity of duocarmycin A and suppresses duocarmycin A-induced apoptosis in human lung carcinoma cells. Int J Biochem Cell Biol. 2007;39(5):988-996. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Duocarmycin A Related Classifications
HY-12455 Related Classifications
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