p53-Y220C stabilizer-1
P53-Y220C stabilizer-1 as an indole-based p53-Y220C stabilizer (EC50 = 0.46 μM) that engages the mutation-induced cavity. P53-Y220C stabilizer-1 binds the p53-Y220C mutant with high affinity (KD = 56 nM) and acts as a selective indole-based p53-Y220C stabilizer that engages the mutation-induced cavity. P53-Y220C stabilizer-1 increases mutant protein thermal stability and restores p53 transcriptional activity, mainly triggering cell cycle arrest instead of acute apoptosis. P53-Y220C stabilizer-1 can be applied to cancers harboring the p53-Y220C mutation, such as gastric cancer.
For research use only. We do not sell to patients.
- Formula: C27H30ClF3N4O3S
- Molecular Weight:583.07
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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p53-Y220C 56 nM (Kd) |
p53-Y220C 46 nM (EC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BXPC-3 | IC50 |
1.6 μM
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Inhibits BXPC-3 cells growth for 3 days.
Inhibits BXPC-3 cells growth for 3 days.
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42268678 |
| NUGC-3 | IC50 |
1.1 μM
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Inhibits NUGC-3 cells growth for 3 days.
Inhibits NUGC-3 cells growth for 3 days.
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42268678 |
| HEK-293T | IC50 |
4.8 μM
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Inhibits HEK-293T cells growth for 3 days.
Inhibits HEK-293T cells growth for 3 days.
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42268678 |
| Huh-7 | IC50 |
2.4 μM
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Inhibits Huh-7 cells growth for 3 days.
Inhibits Huh-7 cells growth for 3 days.
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42268678 |
| NUGC-4 | IC50 |
3.1 μM
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Inhibits NUGC-4 cells growth for 3 days.
Inhibits NUGC-4 cells growth for 3 days.
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42268678 |
P53-Y220C stabilizer-1 (Compound D2) (3 days) exerts stronger antiproliferative activity than PC10709 in NUGC-3 cells with an IC50 of 1.1 μM[1].
P53-Y220C stabilizer-1 (15-30 μM; 2 h) dosing induces dose-dependent CDKN1A, MDM2, BBC3 upregulation, with mild FAS and GADD45A elevation but little change in BAX[1].
P53-Y220C stabilizer-1 (1-3 μM; 72 h) exerts its antitumor efficacy in NUGC-3 cells primarily by enforcing p53-dependent cell cycle checkpoints rather than triggering acute apoptosis[1].
P53-Y220C stabilizer-1 (10 μM; 2 h) enriches PAb1620-positive folded p53 more effectively than PC10709 and reduces misfolded PAb240-reactive p53 in NUGC-3 cells[1].
P53-Y220C stabilizer-1 (10 μM; 6 h) and PC10709 boost p53-Y220C binding to p53-consensus DNA probes, with P53-Y220C stabilizer-1 yielding a stronger signal in NUGC-3 cells[1].
P53-Y220C stabilizer-1 (1-5 μM; 24 h) induces robust, concentration-dependent G0/G1 cell cycle arrest in NUGC-3 cells[1].
P53-Y220C stabilizer-1 (1-5 μM; 24-48 h) suppresses NUGC-3 growth mainly via sustained G0/G1 arrest instead of acute apoptosis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NUGC-3 cells
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Concentration:15 μM, 30 μM
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Incubation Time:2 h
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Result:Elicited dose-dependent upregulation of CDKN1A, MDM2 and BBC3 transcripts following 2 h treatment.
Moderately increased FAS and GADD45A transcript abundance.
Left BAX expression almost unchanged.
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Cell Line:NUGC-3 cells
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Concentration:1 μM, 3 μM
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Incubation Time:72 h
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Result:Elevated Bax protein levels.
Decreased Bcl-2 protein levels.
Decreased caspase-3 protein levels.
Decreased p53 protein levels.
Elevated p21 and PUMA protein levels.
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Cell Line:NUGC-3 cells
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Concentration:10 μM
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Incubation Time:2 h
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Result:Elevated the pool of correctly folded p53 recognized by PAb1620.
Generated a slightly stronger folded p53 signal than PC10709.
Drastically reduced misfolded p53 detected by PAb240.
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Cell Line:NUGC-3 cells
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Concentration:10 μM
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Incubation Time:6 h
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Result:Strengthened the binding of mutant p53-Y220C to p53 consensus DNA probes.
Boosted p53-Y220C DNA recruitment more markedly than PC10709.
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Cell Line:NUGC-3 cells
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Concentration:1 μM, 5 μM
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Incubation Time:24 h
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Result:Induced G0/G1 cell cycle arrest in NUGC-3 cells.
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Cell Line:NUGC-3 cells
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Concentration:1 μM, 3 μM, 5 μM
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Incubation Time:24 h, 48 h
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Result:Induced negligible changes in total apoptotic populations in NUGC-3 cells.
Barely increased early and late Annexin V-positive apoptotic cells compared with DMSO vehicle control.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:6-8-week-old male Balb/C Nude mice were subcutaneously injected with 1 × 106 NUGC-3 cells and administered compounds starting on day 7 post-tumor inoculation
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Dosage:50 mg/kg, 75 mg/kg
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Administration:i.p., once daily, for 21 days
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Result:Reduced tumor size.
Showed no significant toxicity regarding mouse body weight.
RT-qPCR analysis revealed a distinct, dose-dependent induction of canonical p53 target genes.
Leads to an increase in p21 protein levels, while p53 protein decreases.
H&E staining revealed no evidence of necrosis, inflammatory lesions, or significant tissue architecture damage in mice.
Chemical Information
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Molecular Weight 583.07
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Formula C27H30ClF3N4O3S
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SMILES
ClC1=CN(CC(F)(F)F)C2=CC(C#CCNC3=CC=C(S(=O)(C)=O)C=C3OC)=CC(NC4CCN(C)CC4)=C21
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
p53-Y220C stabilizer-1 Related Classifications
HY-184397 Related Classifications
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