| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Caspase-3
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|---|---|
| ln Vitro |
PHA-690509 inhibited ZIKV infection and production in these central nervous system cells (Fig. 4a–c). ZIKV targets astrocytes in the adult mouse brain48. Analysis of ZIKV production upon infection of human astrocytes showed IC50 values around 0.2 μM for both Niclosamide and PHA-690509 (Fig. 4c). Quantification of astrocyte viability showed minimal toxicity of Niclosamide, PHA-690509 and four CDKis at levels lower than 3 μM (Supplementary Fig. 5a). Given the critical role of CDKs in cell cycle regulation, we examined the effect of PHA-690509 and Seliciclib, the most potent CDKi for ZIKV inhibition (Fig. 3d), on hNPC proliferation. ZIKV infection led to a drastic reduction in hNPC proliferation, which was partially rescued by treatment with either compound (Supplementary Fig. 5b). Furthermore, both PHA-690509 (1 μM) and Seliciclib (5 μM) treatment alone had a minimal effect on hNPC proliferation in brain organoids (Supplementary Fig. 5c).PHA-690509 inhibit ZIKV infection in human astrocytes and forebrain-specific hNPCs.
In our in vitro analyses, treatment of PHA-690509 or Seliciclib partially rescued ZIKV-induced reduction of hNPC proliferation and the treatment itself exhibited a minimal effect on hNPC proliferation in brain organoid cultures, which model early human brain development in vitro. The two-drug combination of Emricasan and PHA-690509 exhibited an additive effect in inhibiting caspase-3 activity in SNB-19 cells (Fig. 4d). A similar additive effect was found to preserve astrocyte viability after ZIKV infection (Fig. 4a, e). Notably, Emricasan did not interfere with PHA-690509’s ability to inhibit ZIKV infection in the combination treatment. Nat Med . 2016 Oct;22(10):1101-1107. https://pubmed.ncbi.nlm.nih.gov/27571349/ |
| Enzyme Assay |
First, measurement of intracellular ZIKV RNA levels showed IC50 values of 1.72 μM and 0.37 μM for PHA-690509 and Niclosamide, respectively (Supplementary Fig. 2d–e). Second, both compounds suppressed production of infectious ZIKV particles at sub-micromolar concentrations (Fig. 2e). To investigate the underlying cellular mechanism, we performed time-of-addition experiments in SNB-19 cells (Fig. 3a). Both compounds effectively inhibited ZIKV infection when added either 1 hour before or 4 hours after virus inoculation (Fig. 3b). In contrast, a monoclonal antibody against AXL, a putative ZIKV entry factor39,40, was only effective when added prior to inoculation (Fig. 3b). Furthermore, the reduction of ZIKV RNA by treatment of these compounds was only apparent after the entry phase (0–4 hours after infection), and was correlated with the replication phase (4–24 hours) of the infection cycle (Supplementary Fig. 3). Together, these results indicate that Niclosamide and PHA-690509 inhibit ZIKV infection at a post-entry stage, likely at the viral RNA replication step. Nat Med . 2016 Oct;22(10):1101-1107. https://pubmed.ncbi.nlm.nih.gov/27571349/
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| Cell Assay |
To test the potential toxic effect on hNPC proliferation, day 20 forebrain organoids were also treated with PHA-690509 (1 μM) or Seliciclib (5 μM) for three days without ZIKV exposure. On day 23 (20+3), treated forebrain organoids were pulsed with 10 μM EdU for 1 hour and immediately fixed for analysis.Nat Med . 2016 Oct;22(10):1101-1107. https://pubmed.ncbi.nlm.nih.gov/27571349/
|
| References |
[1]. Repurposing drugs for use against Zika virus infection. SAR QSAR Environ Res. 2018 Feb;29(2):103-115.
[2]. Recent trends in ZikV research: A step away from cure. Biomed Pharmacother. 2017 Jul;91:1152-1159. |
| Additional Infomation |
Zika virus (ZIKV) is a mosquito-borne flavivirus for which there are no vaccines or specific therapeutics. To find drugs active on the virus is a complex, expensive and time-consuming process. The prospect of drug repurposing, which consists of finding new indications for existing drugs, is an interesting alternative to expedite drug development for specific diseases. In theory, drug repurposing is also able to respond much more rapidly to a crisis than a classical drug discovery process. Consequently, the methodology is attractive for vector-borne diseases that can emerge or re-emerge worldwide with the risk to become pandemic quickly. Different drugs, showing various structures, have been repurposed to be used against ZIKV infection. They are reviewed in this study and the conditions for their potential use in practice are discussed.[1]
Zika virus (ZikV) is a member of the Flaviviridae virus family, genus Flavivirus has emerged as a potential threat to human health worldwide. Consequences of vertical infections includes microcephaly with brain and eye anomalies, and adult infections includes Guillain-Barrésyndrome (GBS), brain ischemia, myelitis and meningoencephalitis. To develop a better treatment, many efforts are being made, like drug-repurposing concept for FDA-approved drugs for antiviral activity are screened against ZikV infection and emerging as a promising alternative to expedite drug development and various vaccines like DNA, ZPIV, LAIV, mRNA and AGS-v vaccines have been designed and in under clinical trial phases. Moreover, few pharmacological agents like Mycophenolicacid, Niclosamide, PHA-690509, Emricasan and Bortezomib are most potent anti-ZikV candidates and highly effective single or combining treatment with these drugs. This article reviews the ZikV illness, transmission patterns, pathophysiology of disease, global efforts, challenges and the prospects for the development of vaccines and antiviral agents.[2] |
| Molecular Formula |
C17H21N3O2S
|
|---|---|
| Molecular Weight |
331.434
|
| Exact Mass |
331.135
|
| Elemental Analysis |
C, 61.61; H, 6.39; N, 12.68; O, 9.65; S, 9.67
|
| CAS # |
492445-28-0
|
| PubChem CID |
9902100
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.2±0.1 g/cm3
|
| Index of Refraction |
1.629
|
| LogP |
3.09
|
| SMILES |
CC(C1=CN=C(S1)NC([C@H](C2=CC=C(NC(C)=O)C=C2)C)=O)C
|
| InChi Key |
NFSKEXQRNDSSAN-NSHDSACASA-N
|
| InChi Code |
InChI=1S/C17H21N3O2S/c1-10(2)15-9-18-17(23-15)20-16(22)11(3)13-5-7-14(8-6-13)19-12(4)21/h5-11H,1-4H3,(H,19,21)(H,18,20,22)/t11-/m0/s1
|
| Chemical Name |
(2S)-2-(4-acetamidophenyl)-N-(5-propan-2-yl-1,3-thiazol-2-yl)propanamide
|
| Synonyms |
PHA690509; PHA 690509; (2S)-2-(4-acetamidophenyl)-N-(5-propan-2-yl-1,3-thiazol-2-yl)propanamide; (2S)-2-[4-(Acetylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide; SCHEMBL5725799; NFSKEXQRNDSSAN-NSHDSACASA-N; BCP01953;PHA-690509
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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 | 3.0172 mL | 15.0861 mL | 30.1723 mL | |
| 5 mM | 0.6034 mL | 3.0172 mL | 6.0345 mL | |
| 10 mM | 0.3017 mL | 1.5086 mL | 3.0172 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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