PDL1 degrader-1
Based on 1 Customer Validation
PDL1 degrader-1 is a palmatine-derived PD-L1 degrader. PDL1 degrader-1 interacts with and inhibits deubiquitinase CSN5, inducing PD-L1 Ub/proteasome-dependent degradation. PDL1 degrader-1 can be used for the research of non-small cell lung cancer.
For research use only. We do not sell to patients.
- Purity : 95.25%
- CAS No.: 3122200-59-0
- Formula: C22H25ClN2O4
- Molecular Weight:416.90
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Storage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
PDL1 degrader-1 (10 μM; 24 h) inhibits the expression of PD-L1 protein in H460 cells[1].
PDL1 degrader-1 (10 μM; 9-36 h) reduces PD-L1 protein expression in H460, PC-9, and LLC cells in a time-dependent manner[1].
PDL1 degrader-1 (10 μM) reduces IFN-γ-induced PD-L1 protein expression in HCC827, A549 and H1299 cells after pre-incubation with 5 ng/mL IFN-γ for 24 h[1].
PDL1 degrader-1 (10 μM; 24 h) reduces the PD-L1 protein level in PC-9 cells, and this result is confirmed by immunofluorescence staining[1].
PDL1 degrader-1 (10 μM; 24 h) reduces PD-L1 protein levels in H460, PC-9 and LLC cells without significantly altering PD-L1 mRNA; meanwhile, it cannot reverse the IFN-γ-induced elevation of PD-L1 mRNA in A549, HCC827 and H1299 cells[1].
PDL1 degrader-1 accelerates the degradation of PD-L1 protein under the condition of CHX-mediated protein synthesis blockade[1].
PDL1 degrader-1-induced downregulation of PD-L1 is attenuated by MG132 (HY-13259), while the lysosomal inhibitor CQ fails to reverse this effect; PDL1 degrader-1 simultaneously increases the ubiquitination level of PD-L1[1].
The downregulation of PD-L1 induced by PDL1 degrader-1 can be counteracted by CSN5 overexpression; SPR assays show that PDL1 degrader-1 directly binds to recombinant CSN5 with a KD value of approximately 28.4 μM[1].
Molecular docking and MM/GBSA calculations predict that PDL1 degrader-1 can enter the binding pocket of the CSN5 JAMM domain, with a calculated ΔGbind of -42 kcal/mol, and it is predicted to form hydrogen bonds with Asn158 and Gln162, as well as hydrophobic interactions with Ala109, Tyr114, Leu157, and Phe161[1].
PDL1 degrader-1 (1-100 µM; treatment for 3 days) inhibits cell viability, with IC50 values of 116.8 μM in H460 cells, 81.0 μM in PC-9 cells, and 122.0 μM in LLC cells[1].
PDL1 degrader-1 (10 μM; H460 cells are pretreated for 24 h; subsequently co-cultured with activated T cells for 2 d) reduces the viability of H460 tumor cells in the presence of activated T cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:H460 non-small cell lung cancer cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Significantly suppressed PD-L1 protein expression relative to DMSO control.
Showed greater PD-L1 downregulation than parent compound PMT and other PMT-O9-A derivatives.
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Cell Line:H460, PC-9, and LLC non-small cell lung cancer cells
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Concentration:0, 1, 5, 10, 20, 100 μM
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Incubation Time:24 h
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Result:Decreased PD-L1 protein expression in a dose-dependent manner across all three cell lines.
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Cell Line:H460, PC-9, and LLC non-small cell lung cancer cells
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Concentration:10 μM
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Incubation Time:0, 9, 15, 24, 36 h
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Result:Decreased PD-L1 protein expression in a time-dependent manner across all three cell lines.
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Cell Line:PC-9 non-small cell lung cancer cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Showed a remarkable reduction in green fluorescent signal corresponding to PD-L1 protein compared to DMSO control.
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Cell Line:H460, PC-9, and LLC non-small cell lung cancer cells
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Concentration:1-100 µM
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Incubation Time:3 d
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Result:Exhibited half-maximal inhibitory concentration (IC50) values of 116.8 μM in H460 cells, 81.0 μM in PC-9 cells, and 122.0 μM in LLC cells.
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Cell Line:H460, PC-9, and LLC non-small cell lung cancer cells
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Concentration:10 μM
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Incubation Time:4 d
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Result:Showed negligible cytotoxic effect, with optical density values comparable to DMSO control across all three cell lines over 4 d.
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Cell Line:H460, PC-9, and LLC non-small cell lung cancer cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Showed no significant change in relative PD-L1 mRNA expression compared to DMSO control in all three cell lines.
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Cell Line:HCC827; A549; H1299
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Concentration:PDL1 degrader-1: 10 μM; IFN-γ: 5 ng/mL
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Incubation Time:IFN-γ preincubation: 24 h
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Result:IFN-γ increased PD-L1 protein expression.
Reduced IFN-γ-induced PD-L1 protein expression in HCC827, A549 and H1299 cells.
In Vivo
PDL1 degrader-1 (10 mg/kg; i.p.; once daily for 10 d) reduces the proportion of intratumoral CD3+CD4+ T cells, increases the infiltration of CD3+CD8+ T cells, and elevates the CD8+/CD4+ ratio, producing the greatest increase in the CD8+/CD4+ ratio among the compared PMT derivatives[1].
PDL1 degrader-1 (10 mg/kg; i.p.; once daily; 10 d) increases the levels of IFN-γ, TNF-α and Granzyme B (GrB) in LLC tumor tissues, and the magnitude of elevation is higher than that of other compared PMT derivatives[1].
PDL1 degrader-1 (5 mg/kg; i.p.; once daily for 8 d) inhibits tumor growth in a comparative experiment with another group of LLC tumor-bearing mice, with an IRT of 66%; in the same experiment, the IRT values of DppA1-DTEU-PMT and DppA1 are 89% and 37%, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice, female, 4 weeks old; subcutaneous inoculation of 1 × 106 LLC cells; randomized when average tumor volume reached 50-80 mm3[1]
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Dosage:10 mg/kg
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Administration:i.p.; once daily for 10 d
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Result:Suppressed LLC tumor growth and showed the greatest tumor-growth suppression among the tested PMT derivatives.
Produced a 71% inhibition rate of tumor growth, exceeding PMT-O9-2A (65%) and PMT-O9-3A (68%).
Reduced the percentage of PD-L1-positive cells in tumor tissues.
Reduced the percentage of Ki-67-positive cells in tumor tissues.
Decreased the CD3+CD4+ population within CD45+ tumor-infiltrating T cells.
Increased CD3+CD8+ T-cell infiltration within CD45+ tumor-infiltrating T cells.
Increased the CD8+/CD4+ ratio, with the greatest increase among the tested PMT derivatives.
Increased intratumoral IFN-γ levels.
Increased intratumoral TNF-α levels.
Increased intratumoral GrB levels.
Produced greater increases in IFN-γ, TNF-α and GrB than the other tested PMT derivatives.
Did not cause significant body-weight loss compared with PBS.
Did not cause obvious damage in H&E-stained major organs.
Did not cause notable changes in ALT, AST, CRE or BUN levels.
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Animal Model:C57BL/6 mice, female, 4 weeks old; subcutaneous inoculation of 1 × 106 LLC cells; randomized when average tumor volume reached 50-80 mm3[1]
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Dosage:5 mg/kg
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Administration:i.p.; once daily for 8 d
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Result:Suppressed LLC tumor growth.
Produced a 66% inhibition rate of tumor growth.
Showed a lower IRT than DppA1-DTEU-PMT (89%) and a higher IRT than DppA1 alone (37%).
Chemical Information
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CAS No. 3122200-59-0
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Appearance Solid
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Molecular Weight 416.90
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Formula C22H25ClN2O4
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Color Yellow to brown
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SMILES
COC1=C(C2=C[N+]3=C(C4=CC(OC)=C(C=C4CC3)OC)C=C2C=C1)OCCN.[Cl-]
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
DMSO : 3.33 mg/mL (7.99 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 (sealed storage, away from moisture). 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 (sealed storage, away from moisture). 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)
Purity & Documentation
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Data Sheet (298 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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Handling Instructions (2659 KB)
References
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 (sealed storage, away from moisture). 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 | 2.3987 mL | 11.9933 mL | 23.9866 mL | 59.9664 mL |
| 5 mM | 0.4797 mL | 2.3987 mL | 4.7973 mL | 11.9933 mL |
PDL1 degrader-1 Related Classifications
HY-168530 Related Classifications
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