PROTAC FAK degrader 3
PROTAC FAK degrader 3 is a potent and selective FAK PROTAC degrader with a DC50 of 1.08 nM. PROTAC FAK degrader 3 induces the ubiquitination and proteasomal degradation of FAK by binding to CRBN, thereby blocking oncogenic signaling, specifically upregulating MHC-I to enhance antigen presentation, and subsequently activating CD8+ T cell-mediated antitumor immune responses. PROTAC FAK degrader 3 can be used in related research on hepatocellular carcinoma, ovarian cancer, and breast cancer.
(Pink: FAK ligand (HY-143407); Blue: Cereblon ligand (HY-103596); Black: linker).
For research use only. We do not sell to patients.
- Formula: C48H50N8O9
- Molecular Weight:882.96
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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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Biological Activity
Description
IC50 & Target
[1]|
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| PA-1 | DC50 |
1.08 nM
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Half-maximal degradation of FAK protein in human PA-1 ovarian cancer cells assessed by immunoblot after 24 h of treatment.
Half-maximal degradation of FAK protein in human PA-1 ovarian cancer cells assessed by immunoblot after 24 h of treatment.
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40742040 |
In Vitro
PROTAC FAK degrader 3 (compound D4) (0.14-500 nM; 1-24 h) selectively degrades FAK in PA-1 ovarian cancer cells in a dose- and time-dependent manner, with a DC50 of 1.08 nM[1].
PROTAC FAK degrader 3 (1 μM; 24 h) exhibits a broad FAK protein degradation effect in ID8, 4T1, H22, HEY, MDA-MB-231, and PLC/PRF5 cells[1].
PROTAC FAK degrader 3 (1 μM; 24 h) mediates FAK degradation in PA-1 cells co-treated with E10 or Y15 (HY-12444) in a manner dependent on binding to the FAK kinase domain[1].
PROTAC FAK degrader 3 (1-3 μM; 8-24 h) inhibits FAK autophosphorylation (p-FAK Tyr397) in PA-1 cells without affecting the mRNA transcription level of the PTK2 (FAK) gene[1].
PROTAC FAK degrader 3 (72 h) inhibits cell proliferation in PA-1, HEY, Huh-7, PLC/PRF5 and H22 cells[1].
PROTAC FAK degrader 3 (0.5-3 μM; 24 h-7 days) significantly inhibits cell colony formation, wound healing and invasive capacity in a dose-dependent manner in PA-1 cells, and upregulates the expression of genes related to antigen processing and presentation[1].
PROTAC FAK degrader 3 (3 μM; 72 h) degrades FAK protein and upregulates the expression of cell surface MHC class I molecules in ID8, PA-1, H22 and PLC/PRF5 cells; it also upregulates the expression of cell surface pMHC-I complex (H-2Kb-OVA257-264) in ID8-OVA cells[1].
PROTAC FAK degrader 3 (3 μM; 72 h) promotes CD8+ T cell activation in ID8 and PA-1 cells co-cultured with activated mouse or human CD8+ T cells[1].
PROTAC FAK degrader 3 (3 μM; 72 h, with 36 h of co-culture) promotes antigen-specific CD8+ T cell proliferation in ID8-OVA cells co-cultured with CD8+ T cells from OT-I mice[1].
PROTAC FAK degrader 3 effectively inhibits the kinase activity of purified FAK, with an IC50 of 0.44 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:PA-1
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Concentration:0.14, 0.41, 1.23, 3.70, 11.1, 33.3, 100, 500 nM
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Incubation Time:1, 2, 4, 6, 12, 24 h
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Result:Degraded FAK protein in a concentration-dependent and time-dependent manner.
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Cell Line:PA-1
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Concentration:1 μM
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Incubation Time:0 h, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h
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Result:Inhibited the phosphorylation of FAK (Tyr397).
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Cell Line:PA-1
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Concentration:3 μM
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Incubation Time:24 h
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Result:Did not alter the mRNA expression level of the PTK2 gene.
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Cell Line:PA-1
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Concentration:1, 3 μM
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Incubation Time:7 days
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Result:Significantly inhibited cell colony formation.
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Cell Line:PA-1
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Concentration:1, 3 μM
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Incubation Time:48 h
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Result:Significantly inhibited cell migration.
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Cell Line:PA-1
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Concentration:0.5 μM
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Incubation Time:24 h
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Result:Significantly reduced the number of migrated and invaded cells.
Parmacokinetics
| Species | Dose | Route | Cmax |
|---|---|---|---|
| Mice[1] | 15 mg/kg | i.p. | 94.93 ng/mL |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/cJ mice (6-week-old) were subcutaneously inoculated into the right flank with 1 × 106 H22 hepatocellular carcinoma cells[1]
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Dosage:15 mg/kg
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Administration:i.p.; once daily; for 8 days
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Result:
Significantly suppressed H22 tumor progression in vivo.
Did not significantly affect the mice's body weight, showing good tolerability.
Significantly enhanced the expression of MHC-I molecules (H2-Kd/H2-Dd) on the surface of tumor cells (CD45-) (3.19-fold versus vehicle).
Enhanced T cell cytotoxicity.
Chemical Information
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Molecular Weight 882.96
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Formula C48H50N8O9
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SMILES
O=C1CCC2=C1C(OC3=NC(NC4=CC=C(C=C4OC)C(NC5CCN(CC5)CCCCCCCOC6=C7C(C(N(C7=O)C8C(NC(CC8)=O)=O)=O)=CC=C6)=O)=NC9=C3C=CN9)=CC=C2
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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)
PROTAC FAK degrader 3 Related Classifications
HY-175459 Related Classifications
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