BAY 57-1293HSV helicase-primase inhibitor CAS# 348086-71-5 |
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Quality Control & MSDS
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| Cas No. | 348086-71-5 | SDF | Download SDF |
| PubChem ID | 491941 | Appearance | Powder |
| Formula | C18H18N4O3S2 | M.Wt | 402.49 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | Pritelivir; AIC316 | ||
| Solubility | DMSO : ≥ 33 mg/mL (81.99 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | N-methyl-N-(4-methyl-5-sulfamoyl-1,3-thiazol-2-yl)-2-(4-pyridin-2-ylphenyl)acetamide | ||
| SMILES | CC1=C(SC(=N1)N(C)C(=O)CC2=CC=C(C=C2)C3=CC=CC=N3)S(=O)(=O)N | ||
| Standard InChIKey | IVZKZONQVYTCKC-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C18H18N4O3S2/c1-12-17(27(19,24)25)26-18(21-12)22(2)16(23)11-13-6-8-14(9-7-13)15-5-3-4-10-20-15/h3-10H,11H2,1-2H3,(H2,19,24,25) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | BAY 57-1293 represents a new class of potent inhibitors of herpes simplex virus (HSV) that target the virus helicase primase complex.
IC50 Value: 20 nM (HSV-1) [1]
Target: HSV
in vitro: BAY 57-1293 is nearly two orders of magnitude more potent than acyclovirin vitro and the superiority was even more prominent when the viral load was increased (BAY 57-1293 IC50 = 12 nM, 20 nM and 50 nM; acyclovir IC50 = 1uM, 3M and 10?50 uM at a multiplicity of infection (m.o.i.) of 0.0025, 0.02 and 0.2, respectively). A minor increase in IC50 values at higher viral loads was observed for all thiazolyl compounds listed in Table 1. BAY 57-1293 was also active against porcine (IC50 = 5 uM) and bovine (IC50 = 0.12 uM) herpes strains [1].
in vivo: Delayed treatment with BAY 57-1293 (20 mg/kg 2× daily per os, treatment day 4-14) abrogates progression of disease symptoms (mean of 10 animals per group) of HSV-2 infected guinea pigs within 1 d of treatment and healing is observed subsequently, whereas a 7.5?fold higher dose of valacyclovir (150 mg/kg 2× daily) shows marginal therapeutic efficacy compared with placebo [1]. The compound given orally, or intraperitoneally once per day at a dose of 15 mg/kg for 4 successive days was equally effective or superior to a much higher dose of famciclovir (1mg/ml, i.e. approximately 140-200mg/kg/day) given in the drinking water for 7 consecutive days, which, in our hands, is the most effective method for administering famciclovir to mice [2].
Toxicity: Exploratory toxicology and safety pharmacology studies did not reveal any safety relevant findings at 30, 100 and 300 mg/kg BAY 57-1293 (once daily per os) in a 4-week chronic toxicity study in dogs. However, administration of the same dose to rats for 4 weeks resulted in a dose-dependent transitional hyperplasia of the urinary bladder epithelium [1]. References: | |||||
BAY 57-1293 Dilution Calculator
BAY 57-1293 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.4845 mL | 12.4227 mL | 24.8453 mL | 49.6907 mL | 62.1133 mL |
| 5 mM | 0.4969 mL | 2.4845 mL | 4.9691 mL | 9.9381 mL | 12.4227 mL |
| 10 mM | 0.2485 mL | 1.2423 mL | 2.4845 mL | 4.9691 mL | 6.2113 mL |
| 50 mM | 0.0497 mL | 0.2485 mL | 0.4969 mL | 0.9938 mL | 1.2423 mL |
| 100 mM | 0.0248 mL | 0.1242 mL | 0.2485 mL | 0.4969 mL | 0.6211 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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BAY 57-1293 is a potent and safe inhibitor of HSV helicase-primase with IC50 value of 12nM [1].
BAY 57-1293 displays anti-herpes activity through inhibiting the helicase-primase and affecting the viral DNA synthesis. In the in vitro viral replication assay, BAY 57-1293 shows inhibition against HSV-1 F, HSV-2 G and acyclovir-resistant HSV-1 F mutant with IC50 value of 20nM. In the plaque reduction assay and the conventional cytopathogenicity assay, BAY 57-1293 shows IC50 values of 0.01-0.02μM and 0.01-0.03μM, respectively. Besides that, BAY 57-1293 is active at an IC50 value of 10nM–30nM against all clinical isolates of HSV-1 and HSV-2. Furthermore, BAY 57-1293 is active in vivo. The oral administration of BAY 57-1293 shows 10-fold more potent than valacyclovir in a murine model of disseminated herpes infection. In a rat lethal challenge model, BAY 57-1293 exerts profound antiviral activity without toxic effects. [1, 2]
References:
[1] Kleymann G, Fischer R, Betz U A K, et al. New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease. Nature medicine, 2002, 8(4): 392-398.
[2] Betz U A K, Fischer R, Kleymann G, et al. Potent in vivo antiviral activity of the herpes simplex virus primase-helicase inhibitor BAY 57-1293. Antimicrobial agents and chemotherapy, 2002, 46(6): 1766-1772.
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The helicase-primase inhibitor BAY 57-1293 reduces the Alzheimer's disease-related molecules induced by herpes simplex virus type 1.[Pubmed:23867133]
Antiviral Res. 2013 Sep;99(3):401-4.
Herpes simplex virus type 1 (HSV1) infection of cultured cells causes the formation of beta-amyloid (Abeta) and abnormal tau (P-tau). These molecules comprise the main components of the abnormal protein deposits, amyloid plaques and neurofibrillary tangles, respectively, in Alzheimer's disease (AD) brains, and they have been implicated in disease development. The formation of P-tau, but not of Abeta, depends on viral DNA replication, but nonetheless, three antiviral agents that inhibit HSV1 DNA replication, including acyclovir (ACV), were found to reduce greatly the level of Abeta as well as P-tau, the former probably through prevention of viral spread. Previous studies showed that HSV1 DNA is present and is active in the brain of many elderly people, including AD patients, and that in combination with the type 4 allele of the apolipoprotein E gene, it is likely to play a role in the disease, perhaps via Abeta and P-tau production. With the aim of finding the most suitable antiviral for inhibiting Abeta and P-tau formation as well as HSV1 DNA replication, for future use in a clinical trial for treating AD, we compared the efficacy of ACV with that of another antiviral, BAY 57-1293, which acts by a different mechanism from ACV. We found that BAY 57-1293 is more efficient than ACV not only in inhibiting HSV1 replication, confirming previous studies, but also in decreasing Abeta and P-tau formation. Also, the cell clusters that are formed during infection are reduced in size much more efficiently by BAY 57-1293 than by ACV. These data suggest that BAY 57-1293 would be a more effective agent than ACV for treating AD.
Detection of HSV-1 variants highly resistant to the helicase-primase inhibitor BAY 57-1293 at high frequency in 2 of 10 recent clinical isolates of HSV-1.[Pubmed:17550887]
J Antimicrob Chemother. 2007 Aug;60(2):274-9.
OBJECTIVES: BAY 57-1293 is a helicase-primase inhibitor (HPI) from a new class of antivirals that are highly efficacious in herpes simplex virus (HSV)-1 animal infection models. Resistant mutants with point mutations in the helicase (UL5) were reported to be present in laboratory isolates at a low frequency of approximately 10(-6). In contrast, we have shown elsewhere that some laboratory isolates contain resistant variants at higher frequency (10(-4)). Therefore, we screened 10 recent clinical isolates of HSV-1 for BAY 57-1293-resistant virions. METHODS: Clinical isolates were screened by a plaque reduction assay in Vero cells to determine the frequency of occurrence of BAY 57-1293-resistant variants. The helicase gene for the resistant variants was sequenced. RESULTS: One isolate contained highly resistant variants at 10(-4) and another at 10(-5). Both variants contained a previously reported BAY 57-1293 resistance mutation (K356N) in UL5 and were >5000-fold resistant. CONCLUSIONS: Occurrence of HPI-resistant viruses at high frequency in a clinical isolate is intriguing. Two alternative hypotheses are proposed to explain this phenomenon. It is also surprising that two unrelated clinical isolates contain an identical HPI resistance mutation. These results have important implications for HPI drug-resistance monitoring during subsequent clinical trials.
WITHDRAWN: Synergistic interaction of aciclovir and a helicase-primase inhibitor, BAY 57-1293, against herpes simplex virus type 1.[Pubmed:19168332]
Int J Antimicrob Agents. 2009 Jan 24. pii: S0924-8579(08)00612-2.
This article has been withdrawn at the request of the author(s). The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Single amino acid substitutions in the HSV-1 helicase protein that confer resistance to the helicase-primase inhibitor BAY 57-1293 are associated with increased or decreased virus growth characteristics in tissue culture.[Pubmed:17404685]
Arch Virol. 2007;152(8):1489-500.
Two mutants (BAYr1 and BAYr2) that are 100-fold and >3000-fold resistant, respectively, to the helicase-primase inhibitor (HPI) BAY 57-1293 were derived from a plaque-pure parental strain, HSV-1 SC16 cl-2. BAYr1 has two substitutions in the HSV-1 helicase (UL5) protein (A4 to V; K356 to Q) and BAYr2 has one (G352 to R). It was shown reproducibly that BAYr1 grows to higher titres in tissue culture while BAYr2 grows more slowly than wild-type. Marker transfer experiments confirmed that K356Q and G352R are the drug-resistance mutations and that they are directly associated with differences in virus growth in tissue culture. When BAYr1 was tested in a murine infection model, this virus was shown to be fully pathogenic. We present evidence that single mutations close to a predicted functional domain of an essential HSV-1 replication enzyme (helicase) are associated with drug resistance and virus growth characteristics.
