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Aclarubicin HCl (Aclacinomycin A; Aclaplastin; Jaclacin), the hydrochloride salt of Aclarubicin, is a potent and natually occuring oligosaccharide anthracycline antineoplastic antibiotic extracted 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.
Physicochemical Properties
| Molecular Formula | C42H54CLNO15 |
| Molecular Weight | 848.328860000001 |
| Exact Mass | 847.318 |
| CAS # | 75443-99-1 |
| Related CAS # | Aclacinomycin A;57576-44-0 |
| PubChem CID | 153751 |
| Appearance | Light yellow to yellow solid powder |
| Boiling Point | 897.7ºC at 760 mmHg |
| Melting Point | 151-153℃ |
| Flash Point | 496.7ºC |
| LogP | 3.959 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 16 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 59 |
| Complexity | 1530 |
| Defined Atom Stereocenter Count | 13 |
| SMILES | CC[C@]1(C[C@@H](C2=C(C3=C(C=C2[C@H]1C(=O)OC)C(=O)C4=C(C3=O)C(=CC=C4)O)O)O[C@H]5C[C@@H]([C@@H]([C@@H](O5)C)O[C@H]6C[C@@H]([C@@H]([C@@H](O6)C)O[C@H]7CCC(=O)[C@@H](O7)C)O)N(C)C)O.Cl |
| InChi Key | KUSMIBXCRZTVML-ZRMZNYNWSA-N |
| InChi Code | InChI=1S/C42H53NO15.ClH/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,8,12-13,15-17H2,1-7H31H/t18-,19-,20-,24?,27-,28-,29-,30-,31-,35-,39+,40+,42+/m0./s1 |
| Chemical Name | (1R,2R,4S)-methyl 4-(((2R,5S,6S)-4-(dimethylamino)-5-(((2S,4S,5S,6S)-4-hydroxy-6-methyl-5-(((2R,6S)-6-methyl-5-oxotetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)-2-ethyl-2,5,7-trihydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracene-1-carboxylate hydrochloride |
| Synonyms | Antibiotic MA144A1 ACMA. MA144A1Aclacin AclacinomycineAACM Aclacinomycinclacinon Aclaplastin Jaclacin Aclacinomycin A hydrochloride Aclarubicin Hydrochloride |
| 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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
| ln Vitro | At an IC50 of 52 μM, aclacinomycin A (0-120 μM, 30 min) quantitatively suppresses the rabbit reticulocyte red's ubiquitin-ATP-regulated protein activity. However, it does not prevent ubiquitination [1]. Topo II catalytic activity is inhibited by aclacinomycin A (0-2.4 μM, 3 h) [2]. V79 and irs-2 cell swelling rate is negatively impacted by aclacinomycin A (0-1.8 μM, 3 h) [2]. Bright fluorescent signals are seen in the cytoplasm of human cervical carcinoma HeLa cells upon exposure to aclarithromycin A. Use of a red filter is possible (excitation wavelength: 530-550 nm). |
| ln Vivo | Aclacinomycin A is well absorbed postcervically in mice, stents, and dogs. Side wall LD50 (76.5 mg/kg) Cervical intravenous injection of LD50 (35.6 mg, daily) has an anti-tumor effect on leukemia L-1210 [4]. Akclarithromycin A (0.75-6 mg/kg, IP, daily) exhibits tumor growth in a dose-dependent manner in a mouse-based P-388 model of blood glucose [4]. |
| Cell Assay |
Cell Viability Assay[2] Cell Types: V79 and irs-2 cells Tested Concentrations: 0, 0.006, 0.12, 1.2, and 2.4 μM Incubation Duration: 3 h Experimental Results: Inhibition ./emission wavelength 575 nm) for lung cancer screening [3]. Topo II catalytic activity was dose-dependent. In all cases, the loss of topo II catalytic activity in ACLA-treated cells was significant compared with untreated cells. Cell proliferation assay[2] Cell Types: V79 and irs-2 Cell Tested Concentrations: 0, 0.12, 0.25, 0.37, 0.6, 1.2, 1.8 μM Incubation Duration: 3 hrs (hours) Experimental Results: V79 shows a dose-dependent negative effect on proliferation rate and irs-2 cells, but the reduction in viable colonies was higher in radiosensitive irs-2 cells for most ACLA doses tested. |
| Animal Protocol |
Animal/Disease Models: Multiples of leukemia P-388 [4. /kg) [4]. Doses: 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, 6 mg/kg. Route of Administration: intraperitoneally (ip) (ip) administered daily starting 3 hrs (hrs (hours)) after transplantation for 10 days Experimental Results: Inhibition of tumor growth. Animal/Disease Models: CDF1 mice with leukemia L-1210[4] Doses: 0.6 mg/kg, 1.25 mg/kg, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg Route of Administration: Orally administered, one time/day on days 1-9. Experimental Results: demonstrated anti-tumor effect on leukemia L-1210. |
| 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 |
Aclarubicin hydrochloride is an anthracycline. An anthracycline produced by Streptomyces galilaeus. It has potent antineoplastic activity. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 125 mg/mL (~147.35 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (2.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1788 mL | 5.8939 mL | 11.7879 mL | |
| 5 mM | 0.2358 mL | 1.1788 mL | 2.3576 mL | |
| 10 mM | 0.1179 mL | 0.5894 mL | 1.1788 mL |