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| Targets |
The primary targets of Amustaline 2HCl are nucleic acids, specifically DNA and RNA. The acridine anchor intercalates into nucleic acids non-covalently, bringing the effector bis-alkylator group into proximity with the DNA or RNA. The effector then forms covalent crosslinks between strands of DNA and RNA, preventing replication and transcription. This mechanism effectively inactivates pathogens including viruses, protozoa, and bacteria in red blood cell components. The compound is mainly used for ex vivo purposes for pathogen inactivation in blood components prior to transfusion.
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| ln Vitro |
S-303 (200 μM; 20 h) and glutathione (GSH; 20 mM) inhibit high levels of Chikungunya virus (CHIKV) in RBCs [1]. In whole blood studies, S-303 (200 μM; 20 h) and GSH (2 mM) inhibited >6.5 logs of HIV, >5.7 logs of Bluetongue virus, >7.0 logs of Yersinia enterocolitica, 4.2 logs of Serratia marcescens, and 7.5 logs of Staphylococcus epidermidis [2]. S-303 (200 μM; 20 h) and GSH (20 mM) inhibit the growth of Y. enterocolitica, E. coli, S. marcescens, S. aureus, HIV, bovine viral diarrhoea virus, bluetongue virus, and human adenovirus 5 in RBC by 5 logs or more [2]. S-303 (200 μM; 20 h) maintains in vitro measures of RBC function and physiology (including total ATP, extracellular potassium, hemolysis, glucose consumption, lactate generation, and pH at 37 °C) compared to ordinary RBC[2].
In vitro, Amustaline 2HCl demonstrates potent pathogen inactivation activity. S-303 (200 μM; 20 hours) in combination with glutathione (GSH; 20 mM) inhibits high levels of Chikungunya virus (CHIKV) in red blood cells (RBCs). In whole blood studies, S-303 (200 μM; 20 hours) with GSH (2 mM) inhibited >6.5 logs of HIV, >5.7 logs of Bluetongue virus, >7.0 logs of Yersinia enterocolitica, 4.2 logs of Serratia marcescens, and 7.5 logs of Staphylococcus epidermidis. S-303 (200 μM; 20 hours) with GSH (20 mM) inhibits the growth of Y. enterocolitica, E. coli, S. marcescens, S. aureus, HIV, bovine viral diarrhoea virus, bluetongue virus, and human adenovirus 5 in RBC by 5 logs or more. Importantly, S-303 maintains in vitro measures of RBC function and physiology compared to ordinary RBC, including total ATP, extracellular potassium, hemolysis, glucose consumption, lactate generation, and pH at 37°C. |
| ln Vivo |
Dogs (70 μmol/kg) and rats (50 μmol/kg) both tolerate S-303 RBCs (a single transfusion) well[3]. In rats (10 μmol/kg) and dogs (10 μmol/kg), S-303 RBCs (repeated transfusions) are well tolerated and do not show any histopathologic signs of organ toxicity[3].
In vivo, Amustaline 2HCl-treated RBCs have been evaluated in animal models. Dogs (70 μmol/kg) and rats (50 μmol/kg) both tolerate S-303-treated RBCs (a single transfusion) well. In rats (10 μmol/kg) and dogs (10 μmol/kg), S-303-treated RBCs (repeated transfusions) are well tolerated and do not show any histopathologic signs of organ toxicity. These studies demonstrate the safety of transfusing pathogen-inactivated RBCs. The compound is primarily used ex vivo, and the treated blood components can be safely transfused without significant adverse effects. Further in vivo efficacy studies have demonstrated protection against pathogen transmission. |
| Enzyme Assay |
In vitro enzyme/receptor binding studies for Amustaline 2HCl focus on its nucleic acid intercalation and alkylation properties. The acridine anchor's intercalation into DNA can be assessed using fluorescence spectroscopy, as intercalation causes changes in fluorescence intensity and wavelength. DNA crosslinking can be evaluated using gel electrophoresis, where crosslinked DNA shows reduced mobility. Alkylation activity can be measured using the 4-(4-nitrobenzyl)pyridine (NBP) colorimetric assay, which detects alkylating agents. The labile ester bond hydrolysis at neutral pH can be monitored by HPLC or mass spectrometry. These methods are for research purposes only.
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| Cell Assay |
In vitro cell-based assays for Amustaline 2HCl evaluate pathogen inactivation efficacy and red blood cell quality. Pathogen inactivation is assessed by spiking RBC units with known quantities of pathogens (viruses, bacteria, protozoa) followed by S-303 treatment (200 μM; 20 hours) with GSH (2-20 mM), then measuring residual infectivity via culture or plaque assays. RBC quality is assessed by measuring ATP levels, extracellular potassium, hemolysis, glucose consumption, lactate generation, and pH. Platelet function and plasma protein activity may also be evaluated in relevant studies. Standard cell culture and microbiology techniques are used.
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| Animal Protocol |
In vivo animal studies for Amustaline 2HCl involve transfusion of S-303-treated RBCs into animal models. Rats and dogs receive single or repeated transfusions of S-303-treated RBCs at doses of 10-70 μmol/kg. Animals are monitored for clinical signs, body weight, hematological parameters, and clinical chemistry. Histopathological examination of major organs (liver, kidney, heart, lung, spleen) is performed to assess organ toxicity. Pathogen challenge studies can be performed where animals receive pathogen-spiked RBCs treated with S-303 to demonstrate protection from infection. All procedures must comply with institutional animal care guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Amustaline 2HCl are primarily relevant to its ex vivo use. The compound is added to RBC units and incubated for a defined period (typically 20 hours) before transfusion. The labile ester bond in the linker hydrolyzes at neutral pH to yield non-reactive breakdown products, minimizing the risk of toxicity following transfusion. The acridine anchor and effector components form covalent adducts with nucleic acids, which are removed along with the RBCs during normal clearance. Systemic exposure is minimal as the compound is not administered directly to patients. The compound is for research use only.
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| Toxicity/Toxicokinetics |
Toxicological data for Amustaline 2HCl are derived from preclinical studies in animal models. In rats and dogs, S-303-treated RBCs are well tolerated in both single and repeated transfusions, with no histopathologic signs of organ toxicity observed. The compound is classified for research use only and not for human consumption. The labile ester bond hydrolysis at neutral pH generates non-reactive breakdown products, minimizing potential toxicity. Standard safety precautions for handling alkylating agents apply, including the use of personal protective equipment and working in a chemical fume hood. The compound should be handled with care due to its nucleic acid-targeting properties.
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| References |
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| Additional Infomation |
Amustaline dihydrochloride is the hydrochloride form of Amustaline, a quinacrine mustard gas compound with potential antitumor activity. Amustaline can bind, intercalate, and cross-link with DNA and RNA. This drug is primarily used in in vitro experiments, particularly for inactivating pathogens in red blood cells, such as viruses, protozoa, and bacteria.
Additional information: Amustaline 2HCl is also known as S-303 dihydrochloride. The compound has the CAS number 210584-54-6 and related CAS numbers 220180-88-1, 212335-58-5, and 878189-87-8. It is a yellow to brown solid powder with a boiling point of 575.2°C at 760 mmHg and a flash point of 301.7°C. The compound is composed of an acridine anchor, a bis-alkylator effector, and a linker containing a labile ester bond. Amustaline is a nucleic acid-targeted alkylator that is an efficient pathogen inactivation agent for blood components containing red blood cells. This agent is mainly used for ex vivo purposes for the inactivation of pathogens such as viruses, protozoa, and bacteria in red blood cells. The product is for research use only and is not approved for clinical or therapeutic applications. |
| Molecular Formula |
C22H27CL4N3O2
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| Molecular Weight |
507.28
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| Exact Mass |
505.086
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| CAS # |
210584-54-6
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| Related CAS # |
210584-54-6 (HCl);220180-88-1;212335-58-5 878189-87-8;
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| PubChem CID |
6433103
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| Appearance |
Yellow to brown solid powder
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| Boiling Point |
575.2ºC at 760 mmHg
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| Flash Point |
301.7ºC
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| Vapour Pressure |
3.1E-13mmHg at 25°C
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| LogP |
5.538
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
31
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| Complexity |
469
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WEOLKSYHLNAIRH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H25Cl2N3O2.2ClH/c23-10-13-27(14-11-24)15-16-29-21(28)9-12-25-22-17-5-1-3-7-19(17)26-20-8-4-2-6-18(20)22/h1-8H,9-16H2,(H,25,26)2*1H
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| Chemical Name |
beta-Alanine, N-9-acridinyl-, 2-(bis(2-chloroethyl)amino)ethyl ester, dihydrochloride
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| Synonyms |
S 303 dihydrochloride S 303 HClS-303 S303 S303.
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| HS Tariff Code |
2934.99.9001
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| 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, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 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
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9713 mL | 9.8565 mL | 19.7130 mL | |
| 5 mM | 0.3943 mL | 1.9713 mL | 3.9426 mL | |
| 10 mM | 0.1971 mL | 0.9856 mL | 1.9713 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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