Chromomycin A3
(Synonyms: 色霉素A3,Aburamycin B, CMA3, NSC 58514) 目录号 : GC43266A fluorescent probe and antitumor agent
Cas No.:7059-24-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Chromomycin A3 is an anthraquinone antibiotic and antitumor agent isolated from S. griseus that is used as a fluorescent probe for DNA with excitation/emission spectra of 445/575 nm.[1],[2] Its DNA binding is specific to two or more contiguous GC base pairs, which makes it suitable for characterizing heterochromatin in plants with species-specific AT:GC ratios.[2],[3] Chromomycin A3 is cytotoxic against non-small cell lung cancer and cervical cancer in vitro (IC50s = 1, 42, 60, and 40 nM for HCC44, A549, ME180, and HeLa cells, respectively).[4],[5] It also inhibits oxidative stress- and DNA damage-induced neuronal injury by enhancing Sp1 and Sp3 transcription factor binding.[6]
Reference:
[1]. Crissman, H.A., and Tobey, R.A. Methods in cell biology. 33, (1990).
[2]. Van Dyke, M.W., and Dercan, P.B. Chromomycin, mithramycin, and olivomycin binding sites on heterogeneous deoxyribonucleic acid. Footprinting with (methidiumpropyl-EDTA)iron(II). Biochemistry 22(10), 2373-2377 (1983).
[3]. Schwarzacher, T. Methods in molecular biology. 1370, (2016).
[5]. Miller, S.C., Huang, R., Sakamuru, S., et al. Identification of known drugs that act as inhibitors of NF-κB signaling and their mechanism of action. Biochem. Pharmacol. 79(9), 1272-1280 (2016).
[6]. Chatterjee, S., Zaman, K., Ryu, H., et al. Sequence-selective DNA binding drugs mithramycin A and chromomycin A3 are potent inhibitors of neuronal apoptosis induced by oxidative stress and DNA damage in cortical neurons. Ann. Neurol. 49(3), 345-354 (2001).
| Cas No. | 7059-24-7 | SDF | |
| 别名 | 色霉素A3,Aburamycin B, CMA3, NSC 58514 | ||
| 化学名 | (1S)-1-C-[(2S,3S)-7-[[4-O-acetyl-2,6-dideoxy-3-O-(2,6-dideoxy-4-O-methyl-α-D-lyxo-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy]-3-[[O-4-O-acetyl-2,6-dideoxy-3-C-methyl-α-L-arabino-hexopyranosyl-(1→3)-O-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1→3)-2,6-dideoxy- | ||
| Canonical SMILES | C[C@H]1O[C@@](O[C@@H]2C[C@H](OC3=CC(C=C(C[C@]([C@H](OC)C([C@@H](O)[C@H](O)C)=O)([H])[C@H](O[C@]4([H])O[C@H](C)[C@@H](O)[C@H](O[C@]5([H])O[C@H](C)[C@@H](O)[C@H](O[C@@]6([H])C[C@@](O)(C)[C@@H](OC(C)=O)[C@H](C)O6)C5)C4)C7=O)C7=C8O)=C8C(O)=C3C)O[C@H](C)[C@@H] | ||
| 分子式 | C57H82O26 | 分子量 | 1183.3 |
| 溶解度 | 10 mg/ml in Ethyl Acetate; Soluble in DMSO; Soluble in Ethanol; | 储存条件 | Store at -20°C,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 0.8451 mL | 4.2255 mL | 8.4509 mL |
| 5 mM | 0.169 mL | 0.8451 mL | 1.6902 mL |
| 10 mM | 0.0845 mL | 0.4225 mL | 0.8451 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Chromomycin A3 binds to left-handed poly(dG-m5dC)
Eur J Biochem 1988 Apr 15;173(2):377-82.PMID:3129292DOI:10.1111/j.1432-1033.1988.tb14009.x.
The interaction of Chromomycin A3 (an antitumor antibiotic) with right-handed and left-handed polynucleotides has been studied by absorbance, fluorescence, circular dichroism, 31P-NMR and 1H-NMR techniques. Binding to either the B form of poly(dG-dC) or the Z form of poly(dG-m5dC) shifts the absorbance maximum to higher wavelength and enhances the fluorescence of the drug. Circular dichroic spectra of solutions containing various concentrations of Chromomycin A3 and fixed concentrations of either B or Z polynucleotides show well defined isoelliptic points at similar wavelengths. At the isoelliptic point, the drug complex with B DNA exhibits positive ellipticity while with Z DNA it exhibits negative ellipticity. 31P-NMR spectra of the Chromomycin A3 complex with the Z form of poly(dG-m5dC) demonstrate that the Z conformation is retained in the drug complex up to one molecule drug/four base pairs. At Mg2+ concentrations lower than that necessary to stabilize the left-handed conformation of poly(dG-m5dC) alone, 31P analysis shows that Chromomycin A3 can bind simultaneously to both the B and Z conformations of poly(dG-m5dC), with no effect on the B-Z equilibrium. These data demonstrate that Chromomycin A3 binds to left-handed poly(dG-m5dC) with retention of the left-handed conformation up to saturating drug concentrations.
Chromomycin A3 suppresses cholangiocarcinoma growth by induction of S phase cell cycle arrest and suppression of Sp1‑related anti‑apoptotic proteins
Int J Mol Med 2020 Apr;45(4):1005-1016.PMID:32124934DOI:10.3892/ijmm.2020.4482.
Cholangiocarcinoma (CCA) is a cancer of biliary epithelium. Late diagnosis and resistance to conventional chemotherapy are the major obstacles in CCA treatment. Increased expression of anti‑apoptotic proteins are observed in CCA, which might confer chemoresistance. Thus, modulations of anti‑apoptotic proteins leading to apoptotic induction is the focus of this study. Chromomycin A3 (CMA3), an anthraquinone glycoside‑mithramycin A analog, was selected. CMA3 strongly binds to GC‑rich regions in DNA, where specificity protein 1 (Sp1), a common transcription factor of apoptosis‑related proteins, is preferentially bounded. The effects of CMA3 on anti‑proliferation, cell cycle arrest and apoptosis induction in CCA cells were demonstrated by MTT assay, flow cytometry and western blot analysis. The results showed CMA3 suppressed cell proliferation in vitro in the nM range. At low doses, CMA3 inhibited cell cycle progression at S phase, while it promoted caspase‑dependent apoptosis at higher doses. CMA3 induced effects of apoptosis were through the suppression of Sp1‑related anti‑apoptotic proteins, FADD‑like IL‑1β‑converting enzyme‑inhibitory protein, myeloid cell leukemia‑1, X‑linked inhibitor of apoptosis protein, cellular inhibitor of apoptosis and survivin. The anti‑CCA effects of CMA3 were confirmed in the xenograft mouse model. CMA3 retarded xenograft tumor growth. Taken together, CMA3 induced apoptosis in CCA cells by diminishing the Sp1‑related anti‑apoptotic proteins is demonstrated. CMA3 might be useful as a chemosensitizing agent.
Chromomycin A3 as a fluorescent probe for flow cytometry of human gynecologic samples
J Histochem Cytochem 1977 Jul;25(7):573-9.PMID:70448DOI:10.1177/25.7.70448.
Chemical, physical and optical properties of Chromomycin A3 are examined so as to ascertain appropriate staining and analysis procedures for flow cytometry of human gynecologic samples. Fluorescence excitation and emission spectra of chromomycin A3-stained cervical cells are compared with those of chromomycin A3-stained deoxyribonucleic acid. Conditions for deoxyribonucleic acid-specific staining of cervical cells are presented, and staining specificity of cervical cells with Chromomycin A3 is compared to that obtained with ethidium bromide, propidium iodide and Hoechst 33258. Also presented is a brief review of two parameter flow cytometry as a prescreening procedure for detection of cervical neoplasia. Results of flow cytometry and cell sorting are interpreted based on the deoxyribonucleic acid-specificity of Chromomycin A3 staining.
Role of magnesium ion in the interaction between Chromomycin A3 and DNA: binding of chromomycin A3-Mg2+ complexes with DNA
Biochemistry 1992 Mar 24;31(11):2988-97.PMID:1550824DOI:10.1021/bi00126a021.
Chromomycin A3 is an antitumor antibiotic which blocks macromolecular synthesis via reversible interaction with DNA template only in the presence of divalent metal ions such as Mg2+. The role of Mg2+ in this antibiotic-DNA interaction is not well understood. We approached the problem in two steps via studies on the interaction of (i) Chromomycin A3 and Mg2+ and (ii) chromomycin A3-Mg2+ complex(es) and DNA. Spectroscopic techniques such as absorption, fluorescence, and CD were employed for this purpose. The results could be summed up in two parts. Absorption, fluorescence, and CD spectra of the antibiotic change upon addition of Mg2+ due to complex formation between them. Analysis of the quantitative dependence of change in absorbance of Chromomycin A3 (at 440 nm) upon input concentration of Mg2+ indicates formation of two types of complexes with different stoichiometries and formation constants. Trends in change of fluorescence and CD spectroscopic features of the antibiotic in the presence of Mg2+ at different concentrations further corroborate this result. The two complexes are referred to as complex I (with 1:1 stoichiometry in terms of Chromomycin A3:Mg2+) and complex II (with 2:1 stoichiometry in terms of Chromomycin A3:Mg2+), respectively, in future discussions. The interactions of these complexes with calf thymus DNA were examined to check whether they bind differently to the same DNA. Evaluation of binding parameters, intrinsic binding constants, and binding stoichiometry, by means of spectrophotometric and fluorescence titrations, shows that they are different. Distinctive spectroscopic features of complexes I and II, when they are bound to DNA, also support that they bind differently to the above DNA. Measurement of thermodynamic parameters characterizing their interactions with calf thymus DNA shows that complex I-DNA interaction is exothermic, in contrast to complex II-DNA interaction, which is endothermic. This feature implies a difference in the molecular nature of the interactions between the complexes and calf thymus DNA. These observations are novel and significant to understand the antitumor property of the antibiotic. They are also discussed to provide explanations for the earlier reports that in some cases appeared to be contradictory.
NMR studies of Chromomycin A3 interaction with DNA
Biochemistry 1985 Nov 19;24(24):6887-93.PMID:2416346DOI:10.1021/bi00345a022.
The binding of Chromomycin A3 to calf thymus DNA and poly(dG-dC) has been studied by 13C and 1H NMR with emphasis on the mode of binding, the role of Mg2+, and pH effects. The most prominent changes in the DNA base pair 13C NMR resonances upon complexation with chromomycin were observed for G and C bases, consistent with the G-C preference exhibited by this compound. Comparison of the 13C spectrum of DNA-bound Chromomycin A3 with that of DNA-bound actinomycin D, a known intercalator, showed many similarities in the base pair resonances. This suggested the possibility that Chromomycin A3 binds via an intercalative mechanism. 1H NMR studies in the imino proton, low-field region of the spectrum provided additional evidence in support of this binding mode. In the low-field spectrum of Chromomycin A3 bound to calf thymus DNA, a small shoulder was observed on the upfield side of the G-C imino proton peak. Similarly, in the Chromomycin A3 complex with poly(dG-dC), a well-resolved peak was found upfield from the G-C imino proton peak. These results are expected for ligands that bind by intercalation. Furthermore, in both the calf thymus and poly(dG-dC) drug complexes (in the presence of Mg2+) a broad peak was also present downfield (approximately 16 ppm from TSP) from the DNA imino protons. This was attributed to the C-9 phenolic hydroxyl proton on the chromomycin chromophore. Visible absorbance spectra at different pH values showed that the role of Mg2+ in the binding of Chromomycin A3 to DNA is more than simple neutralization of the drug's anionic change.