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| 5mg |
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Purity: ≥98%
lRifalazil (formerly known as KRM-1648 and AMI-1648) is a rifamycin analog and an antibiotic. Rifalazil kills bacterial cells by blocking off the β-subunit in RNA polymerase. Rifalazil is used as treatments for many different diseases. Of the most common are Chlamydia infection, Clostridium difficile associated diarrhea (CDAD), and tuberculosis (TB).
| ln Vitro |
Rifalazil inhibits Clostridium difficile, Clostridium perfringens, and Bacteroides fragilis, with MIC50 values of 0.0015, 0.0039, and 0.0313 µg/ml, respectively. It shows antibacterial action against Gram-positive gut bacteria [3]. MIC50 values of 16 and 16 µg/ml, respectively, show that rifalazil inhibits Escherichia coli and Klebsiella pneumoniae, two Gram-negative enteric bacteria [3]. The antibacterial activity of Rifalazil is directed against gram-positive bacteria that are not found in the intestinal tract. Specifically, it inhibits the growth of methicillin-sensitive, methicillin-resistant, methicillin-and quinolone-resistant Staphylococcus aureus, and Staphylococcus epidermidis cocci. The MIC50 values of these bacteria are 0.0078, 0.0078, 0.0078, 0.0078, 0.0002, and 0.0001 µg/ml, respectively [3]. With MIC50 values of 0.004, 0.000125, and 0.00025 µg/ml, respectively, rifalazil exhibits antibacterial activity against Helicobacter pylori, Chlamydia pneumoniae, and Chlamydia trachomatis [3].
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| ln Vivo |
There was a significant decrease in the number of spleens in each group of mice in which Mycobacterium tuberculosis was detected when rifalazil (oral gavage; 20, 25, and 150 mg/kg; 6-8 weeks) was combined with isoniazid (INH) for at least 6 weeks. This was in contrast to the reduction in early and late controls. Furthermore, the addition of pyrazinamide (PZA) did not significantly improve RLZ-INH treatment at any point in time [2].
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| Animal Protocol |
Animal/Disease Models: Female CD-1 mice infected with 5.2×107 live mycobacteria [2]
Doses: 20, 25 and 150 mg/kg; 6-8 weeks Route of Administration: po (oral gavage) Experimental Results: with isoniazid (INH) combination shows its potential for short-term treatment of Mycobacterium tuberculosis infection. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
The major metabolites of rifalazil in human are 25-deacetyl-benzoxazinorifamycin and 32-hydroxy-benzoxazinorifamycin. The enzyme responsible for the benzoxazinorifamycin-25-deacetylation is a B-esterase while the enzyme responsible for the benzoxazinorifamycin-32-hydroxylation is CYP3A4. |
| References | |
| Additional Infomation |
Rifalazil is a phenoxazine.
Rifalazil is a derivative of the antibiotic rifamycin. It is being investigated by ActivBiotics for the treatment of various bacterial infections. Drug Indication Investigated for use/treatment in atherosclerosis, bacterial infection, and peripheral vascular disease. Mechanism of Action The potent antimycobacterial activity of rifalazil is due to inhibition of bacterial RNA polymerase. Pharmacodynamics Rifalazil represents a new generation of ansamycins that contain a unique four-ring structure. Originally rifalazil was developed as a therapeutic agent to replace rifampin as part of a multiple drug regimen in the treatment of tuberculosis. As a result of its superior antimicrobial activity and high intracellular levels, rifalazil has potential to treat indications caused by the intracellular pathogen, Chlamydia trachomatis, which causes non-gonococcal urethritis and cervicitis, often leading to pelvic inflammatory disease. Rifalazil also has potential to treat the related microorganism, Chlamydia pneumoniae, which may be involved in chronic inflammatory processes thought to be partly responsible for atherosclerosis. Due to its favourable antimicrobial spectrum and other positive attributes, rifalazil may also prove valuable in the treatment of gastric ulcer disease, caused by Helicobacter pylori, and antibiotic-associated colitis, the result of toxin production following the growth of Clostridium difficile in the colon. The potential value of rifalazil in the treatment of these indications will be assessed in human clinical trials. |
| Molecular Formula |
C51H64N4O13
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|---|---|
| Molecular Weight |
941.088
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| Exact Mass |
940.447
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| CAS # |
129791-92-0
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| Related CAS # |
129791-92-0;
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| PubChem CID |
135431094
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| Appearance |
Blue to dark blue solid powder
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| Density |
1.36g/cm3
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| Boiling Point |
1048.6ºC at 760mmHg
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| Melting Point |
195-200° (dec)
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| Flash Point |
588ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.634
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| LogP |
6.573
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
68
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| Complexity |
2510
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| Defined Atom Stereocenter Count |
9
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| SMILES |
C[C@H]1/C=C/C=C(\C(=O)NC2=C3C(=C4C(=C(C(=C5C4=C([C@](O5)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)O)C)O)C2=O)N=C6C(=CC(=CC6=O)N7CCN(CC7)CC(C)C)O3)/C
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| InChi Key |
UEFHFKKWYKVLDC-HTQYORAHSA-N
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| InChi Code |
InChI=1S/C51H64N4O13/c1-24(2)23-54-16-18-55(19-17-54)32-21-33(57)39-35(22-32)67-48-40(52-39)36-37-44(60)30(8)47-38(36)49(62)51(10,68-47)65-20-15-34(64-11)27(5)46(66-31(9)56)29(7)43(59)28(6)42(58)25(3)13-12-14-26(4)50(63)53-41(48)45(37)61/h12-15,20-22,24-25,27-29,34,42-43,46,57-60H,16-19,23H2,1-11H3,(H,53,63)/b13-12+,20-15+,26-14-/t25-,27+,28+,29+,34-,42-,43+,46+,51-/m0/s1 SMILES
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| Chemical Name |
(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,32-Tetrahydroxy-30-(4-isobutyl-1-piperazinyl)-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,37-trioxo-8,27,38-trioxa-24,34-diazahexacyclo[23.11.1.14,7.05,36.026,35.028,33]octatriaconta-1(36),2,4,9,19,21,25,28,30,32,34-undecaen-13-yl acetate
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| Synonyms |
Rifalazil ABI 1648 ABI1648 ABI -648 Krm-1648 Krm 1648 Krm1648
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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) |
DMSO : ~8.33 mg/mL (~8.85 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.2 mg/mL (2.34 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 22.0 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: ≥ 2.2 mg/mL (2.34 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 22.0 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 | 1.0626 mL | 5.3130 mL | 10.6260 mL | |
| 5 mM | 0.2125 mL | 1.0626 mL | 2.1252 mL | |
| 10 mM | 0.1063 mL | 0.5313 mL | 1.0626 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00385385 | UNKNOWN STATUS | Drug: Rifalazil | Cerebrovascular Disease Coronary Artery Disease Peripheral Vascular Disease |
ActivBiotics | 2006-10 | Phase 2 |
| NCT00251849 | UNKNOWN STATUS | Drug: Rifalazil | Intermittent Claudication Peripheral Vascular Diseases |
ActivBiotics | 2005-11 | Phase 3 |
| NCT01631201 | COMPLETED | Drug: Rifalazil 25 milligram Drug: Azithromycin 1 gram |
Chlamydia Trachomatis Infection | ActivBiotics Pharma, LLC | 2012-07 | Phase 2 |
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