UNI418
Based on 1 Customer Validation
UNI418 is an orally active and potent PIKfyve and PIP5K1C inhibitor with Kd values of 0.78 and 61 nM, respectively. UNI418 exhibits anti-SARS-CoV-2 activity with an EC50 of 1.4 μM. UNI418, through inhibition of PIKfyve and PIP5K1C (IC50 = 60.1 nM), on one hand reduces IP6 levels to trigger Cul4A-WDR5-dependent homologous recombination protein degradation, and on the other hand impairs endolysosomal acidification, cathepsin L maturation, and ACE2-mediated endocytosis, thereby blocking SARS-CoV-2 entry and escape. UNI418 can be used for research on ovarian cancer and SARS-CoV-2 infection.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 99.61%
- CAS No.: 1802068-51-4
- Formule: C22H16N6
- Masse moléculaire:364.40
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
[2]|
PIP5K1C 61 nM (Kd) |
PIP5K1C 60.1 nM (IC50) |
PIP5K1B 60.7 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCT-116 | IC50 |
1.65 μM
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Cytotoxicity against human HCT116 cells assessed as viability reduction after 72 hrs incubation by CellTiter-Glo assay.
Cytotoxicity against human HCT116 cells assessed as viability reduction after 72 hrs incubation by CellTiter-Glo assay.
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41935081 |
| HCT-116 | IC50 |
0.44 μM
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Cytotoxicity against human HCT116 PARP1−/− cells assessed as viability reduction after 72 hrs incubation by CellTiter-Glo assay.
Cytotoxicity against human HCT116 PARP1−/− cells assessed as viability reduction after 72 hrs incubation by CellTiter-Glo assay.
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41935081 |
| Vero | EC50 |
1.4 μM
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Antiviral activity against SARS-CoV-2 in Vero cells assessed by immunofluorescence counting of spike-positive cells 2 days postinfection.
Antiviral activity against SARS-CoV-2 in Vero cells assessed by immunofluorescence counting of spike-positive cells 2 days postinfection.
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39085352 |
| Vero | CC50 |
62.3 μM
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Cytotoxicity against Vero cells assessed by MTT assay 2 days postinfection.
Cytotoxicity against Vero cells assessed by MTT assay 2 days postinfection.
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39085352 |
| PEO1 | IC50 |
6.83 μM
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Clonogenic survival inhibition against PEO-1 cells by UNI418 assessed by methylene blue staining.
Clonogenic survival inhibition against PEO-1 cells by UNI418 assessed by methylene blue staining.
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41935081 |
| LNCaP C4-2 | IC50 |
4.44 μM
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Clonogenic survival inhibition against C4-2 cells by UNI418 assessed by methylene blue staining.
Clonogenic survival inhibition against C4-2 cells by UNI418 assessed by methylene blue staining.
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41935081 |
| CAPAN-1 | IC50 |
18.20 μM
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Clonogenic survival inhibition against Capan-1 cells by UNI418 assessed by methylene blue staining.
Clonogenic survival inhibition against Capan-1 cells by UNI418 assessed by methylene blue staining.
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41935081 |
In Vitro
UNI418 (0.5 μM; 18 h) induces degradation of homologous recombination proteins (RAD51, CHK1, and CtIP) in RPE1 and HCT116 cells[1].
UNI418 (up to 5 μM; 72 h) selectively kills PARP1-deficient HCT116 cells with an IC50 of 0.44 μM versus 1.65 μM in WT cells, and acts synergistically with Olaparib (HY-10162)[1].
UNI418 shows stronger inhibitory activity against HCT116 PARP1-/- (IC50 = 0.44 μM) than against HCT116 WT (IC50 = 1.65 μM), with IC50 values of 4.44 μM, 5.39 μM, 6.83 μM, and 18.20 μM in C4-2, C2-2, PEO-1, and Capan-1 cells, respectively.[1]
UNI418 (0.5 μM-1 μM; 2 h) induces SQSTM1/p62 and LC3-II accumulation in RPE1 cells and significantly inhibits autophagic flux[2].
UNI418 (0.005-100 μM; 2 days) inhibits SARS-CoV-2 infection in Vero cells with an EC50 of 1.4 μM and a CC50 of 62.3 μM (selectivity index 45.6)[2].
UNI418 (0.001-10 μM; 24 h) significantly reduces viral genome copy numbers in the supernatant and decreases intracellular viral nucleocapsid protein (NP) expression in Vero cells infected with SARS-CoV-2 (MOI 0.001)[2].
UNI418 (0.125-0.5 μM; pretreatment for 1 h, observation for 24 h) significantly inhibits the entry of Wuhan-Hu-1, Delta, and Omicron variant spike pseudoviruses in 293T-ACE2 cells[2].
UNI418 (0.5 μM; 30 min pretreatment, 2 h observation after treatment) successfully inhibits spike-RBD-induced ACE2-mediated endocytosis in hACE2-GFP-transfected HEK293T cells[2].
UNI418 (0.01-10 μM; 1-3 h post-infection) dose-dependently inhibits the reduction of endogenous full-length ACE2 caused by viral infection in SARS-CoV-2-infected Vero cells[2].
UNI418 (1 h) directly binds to and inhibits PIKfyve and PIP5K1C, with KD values of 0.74 nM and 61 nM, respectively[1].
UNI418 (0.25-5 μM; 24 h) inhibits the DNA replication stress response in HEK293T Luc-ATAD5 cells[1].
UNI418 promotes the protein degradation of RAD51, CHK1, and CtIP without altering their mRNA levels[1].
UNI418 exhibits inhibitory activity against PIKfyve (Kd = 0.78 nM), PIP5K1C (Kd = 61 nM, IC50 = 60.1 nM), and PIP5K1B (IC50 = 60.7 nM) in in vitro cell-free kinase assays[2].
UNI418 (1 μM; 1 h) inhibits endosomal/lysosomal acidification and induces vacuolization in Vero cells[2].
UNI418 (0.5-10 μM) inhibits cathepsin D (Cathepsin D) and cathepsin L (Cathepsin L) proteolytic maturation in Vero81/Vero cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RPE1 cells
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Concentration:0.5, 1 μM
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Incubation Time:2 h
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Result:Strongly induced the accumulation of SQSTM1/p62 and LC3-II, and markedly inhibited autophagic flux under both normal and starvation conditions
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Cell Line:stable mCherry-GFP-LC3 expressing HEK293T cells
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Concentration:0.5 μM
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Incubation Time:1, 3, 6 h
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Result:Considerably increased the number of nonacidic autophagosomes (yellow fluorescence), suggesting inhibition of autophagosome-lysosome fusion or lysosomal acidification.
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Cell Line:Vero81/Vero cells
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Concentration:0.5, 1, 10 μM
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Incubation Time:4 h
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Result:Inhibited the proteolytic maturation of both cathepsin D and cathepsin L, and largely reduced the lysosomal targeting of cathepsin D (LAMP1 colocalization).
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Cell Line:Vero cells
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Concentration:0.001, 0.01, 0.1, 1, 10 μM
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Incubation Time:24 hours postinfection
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Result:Drastically reduced the viral genome copies in culture supernatants (by an approximately 2-log reduction at 10 μM).
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Cell Line:RPE1 and HCT116 cells
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Concentration:0.5 μM
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Incubation Time:18 h
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Result:Significantly reduced the protein levels of RAD51, CHK1, and CtIP in both soluble and chromatin-bound fractions without affecting their mRNA levels; promoted Cul4A-dependent proteasomal degradation.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.CB17-Prkdcscid/J (male, 6 weeks old) were subcutaneously injected with HCT116 WT or PARP1-/- colon cancer cellsinto the right flank[1]
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Dosage:10 mg/kg
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Administration:s.c.; once every other day; 12 days
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Result:Markedly suppressed tumor growth exclusively in the PARP1-/- xenografts, with no significant effect observed in the WT tumors.
Resulted in the significant inhibition of HCT116 WT tumor growth when co-administered with Olaparib (50 mg/kg), demonstrating an in vivo synergistic effect.
Caused no significant alteration in the body weights of the mice throughout the treatment period, either alone or in combination, indicating good tolerability.
Chemical Information
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CAS No. 1802068-51-4
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Appearance Solid
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Masse moléculaire 364.40
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Formule C22H16N6
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Color Off-white to light brown
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SMILES
C1(C2=CC=NC=C2)=NC(NC3=NNC(C4=CC=CC=C4)=C3)=C5C=CC=CC5=N1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 50 mg/mL (137.21 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureté et documentation
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Fiche technique (301 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7442 mL | 13.7212 mL | 27.4424 mL | 68.6059 mL |
| 5 mM | 0.5488 mL | 2.7442 mL | 5.4885 mL | 13.7212 mL | |
| 10 mM | 0.2744 mL | 1.3721 mL | 2.7442 mL | 6.8606 mL | |
| 15 mM | 0.1829 mL | 0.9147 mL | 1.8295 mL | 4.5737 mL | |
| 20 mM | 0.1372 mL | 0.6861 mL | 1.3721 mL | 3.4303 mL | |
| 25 mM | 0.1098 mL | 0.5488 mL | 1.0977 mL | 2.7442 mL | |
| 30 mM | 0.0915 mL | 0.4574 mL | 0.9147 mL | 2.2869 mL | |
| 40 mM | 0.0686 mL | 0.3430 mL | 0.6861 mL | 1.7151 mL | |
| 50 mM | 0.0549 mL | 0.2744 mL | 0.5488 mL | 1.3721 mL | |
| 60 mM | 0.0457 mL | 0.2287 mL | 0.4574 mL | 1.1434 mL | |
| 80 mM | 0.0343 mL | 0.1715 mL | 0.3430 mL | 0.8576 mL | |
| 100 mM | 0.0274 mL | 0.1372 mL | 0.2744 mL | 0.6861 mL |
UNI418 Related Classifications
HY-163943 Related Classifications
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