 Chemical Structure.png)
Aclarubicin (Aclacinon; Aclacin; Aclaplastin; Aclacinomycine; Jaclacin. ACM; Aclacinomycin A) is a natually occuring oligosaccharide and anthracycline anticancer antibiotic isolated from the bacterium Streptomyces galilaeus. Aclarubicin inhibits the synthesis of RNA and proteins as well as DNA replication and repair. It does this by intercalating into DNA and interacting with topoisomerases I and II.
Physicochemical Properties
| Molecular Formula | C42H53NO15 |
| Molecular Weight | 811.87 |
| Exact Mass | 811.342 |
| Elemental Analysis | C, 62.14; H, 6.58; N, 1.73; O, 29.56 |
| CAS # | 57576-44-0 |
| Related CAS # | 57576-44-0; 75443-99-1 (HCl) |
| PubChem CID | 451415 |
| Appearance | Solid powder |
| Density | 1.42 g/cm3 |
| Boiling Point | 897.7ºC at 760 mmHg |
| Melting Point | 151-153ºC |
| Flash Point | 496.7ºC |
| Index of Refraction | 1.629 |
| LogP | 3.157 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 16 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 58 |
| Complexity | 1530 |
| Defined Atom Stereocenter Count | 13 |
| SMILES | O([C@H]1C[C@@H]([C@@H]([C@H](C)O1)O[C@H]1C[C@@H]([C@@H]([C@H](C)O1)O[C@H]1CCC([C@H](C)O1)=O)O)N(C)C)[C@@H]1C2=C(C3C(C4C(=CC=CC=4C(C=3C=C2[C@@H](C(=O)OC)[C@@](CC)(C1)O)=O)O)=O)O |
| InChi Key | USZYSDMBJDPRIF-SVEJIMAYSA-N |
| InChi Code | InChI=1S/C42H53NO15/c1-8-42(51)17-28(33-22(35(42)41(50)52-7)14-23-34(38(33)49)37(48)32-21(36(23)47)10-9-11-26(32)45)56-30-15-24(43(5)6)39(19(3)54-30)58-31-16-27(46)40(20(4)55-31)57-29-13-12-25(44)18(2)53-29/h9-11,14,18-20,24,27-31,35,39-40,45-46,49,51H,8,12-13,15-17H2,1-7H3/t18-,19-,20-,24-,27-,28-,29-,30-,31-,35-,39+,40+,42+/m0/s1 |
| Chemical Name | methyl (1R,2R,4S)-4-[(2R,4S,5S,6S)-4-(dimethylamino)-5-[(2S,4S,5S,6S)-4-hydroxy-6-methyl-5-[(2R,6S)-6-methyl-5-oxooxan-2-yl]oxyoxan-2-yl]oxy-6-methyloxan-2-yl]oxy-2-ethyl-2,5,7-trihydroxy-6,11-dioxo-3,4-dihydro-1H-tetracene-1-carboxylate |
| Synonyms | Aclacinon; Aclacin; Aclaplastin; Aclacinomycine Jaclacin; ACMA; clacinomycin A |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Topoisomerase II; Topoisomerase I |
| ln Vitro |
Aclacinomycin A (0-120 μM, 30 min) has an IC50 of 52 μM and suppresses rabbit reticulocytes' ubiquitin-ATP-dependent proteolytic activity in a dose-dependent reaction. On the other hand, it does not prevent ubiquitination [1]. Aclacinomycin A prevents ubiquitin-ATP-dependent proteolysis subsequent to ubiquitin's conjugation with proteins[1]. Aclacinomycin A (zero-2.4 μM, three hours) inhibits the catalytic activity of topo II [2]. Aclacinomycin A (0-1.8 μM, 3 h) inhibits the rate of V79 and irs-2 cell proliferation[2]. Aclacinomycin A emits fluorescence, and when fluorescence microscopy is carried out with the red filter (excitation 530-550 nm/emission 575 nm), human cervical cancer HeLa cells exposed to Aclacinomycin A show bright fluorescence signals in the cytoplasm[3]. |
| ln Vivo |
Aclacinomycin A (0.75-6 mg/kg, IP, daily) dose-dependently displays tumor growth in mice-based Leukemia P-388 model[4]. Aclacinomycin A (0.6-20 mg/kg, Orally, daily) shows an antitumor effect on leukemia L-1210[4]. Aclacinomycin A is highly well absorbed when given orally to mice, rats, and dogs. In mice, the oral LD50 (76.5 mg/kg) is approximately twice that of the IV LD50 (35.6 mg/kg)[4]. |
| Cell Assay |
ell Line: V79 and irs-2 cells Concentration: 0, 0.006, 0.12, 1.2, and 2.4 μM Incubation Time: 3 h Result: Inhibited the topo II catalytic activity in a dose-dependent manner. The loss of topo II catalytic activity in ACLA-treated cells was in all cases significant compared with non-treated cells. |
| Animal Protocol |
DBA/2, CDF1 (BALB/c×DBA/2) mice with Leukemia P-388 (90-110 g). 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, 6 mg/kg Intraperitoneal administration daily for 10 days starting 3 hr after transplantation. |
| References |
[1]. Inhibition of different steps of the ubiquitin system by CDDP and aclarubicin. Biochim Biophys Acta. 1992 Sep 15;1117(2):131-5. [2]. Induction of genotoxic and cytotoxic damage by aclarubicin, a dual topoisomerase inhibitor. Mutat Res. 2005 May 2;583(1):26-35. [3]. Aclarubicin, an anthracycline anti-cancer drug, fluorescently contrasts mitochondria and reduces the oxygen consumption rate in living human cells. Toxicol Lett. 2017 Aug 5;277:109-114. [4]. Antitumor activity of new anthracycline antibiotics, aclacinomycin-A and its analogs, and their toxicity. Gan. 1977 Oct;68(5):685-90. |
| Additional Infomation |
Aclacinomycin A is an anthracycline antibiotic that is produced by Streptomyces galilaeus and also has potent antineoplastic activity. It has a role as an antimicrobial agent, an EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor, an apoptosis inducer, an antineoplastic agent and a bacterial metabolite. It is an anthracycline, an aminoglycoside, a trisaccharide derivative, a polyketide, a member of phenols, a methyl ester and a member of tetracenequinones. It is functionally related to an aklavinone. It is a conjugate base of an aclacinomycin A(1+). It is a tautomer of an aclacinomycin A zwitterion. Aclarubicin has been reported in Streptomyces galilaeus, Streptomyces bobili, and Micromonospora with data available. Aclarubicin is an oligosaccharide anthracycline antineoplastic antibiotic isolated from the bacterium Streptomyces galilaeus. Aclarubicin intercalates into DNA and interacts with topoisomerases I and II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. Aclarubicin is antagonistic to other agents that inhibit topoisomerase II, such as etoposide, teniposide and amsacrine. This agent is less cardiotoxic than doxorubicin and daunorubicin. An anthracycline produced by Streptomyces galilaeus. It has potent antineoplastic activity. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2317 mL | 6.1586 mL | 12.3172 mL | |
| 5 mM | 0.2463 mL | 1.2317 mL | 2.4634 mL | |
| 10 mM | 0.1232 mL | 0.6159 mL | 1.2317 mL |