10-SLF
10-SLF is an FKBP12 PROTAC degrader. 10-SLF covalently interacts with the cysteine residue of FBXW7R465C, forms a ternary complex with FKBP12, and promotes FBXW7-R465C-dependent proteasomal degradation of FKBP12. 10-SLF can be used for the research of pancreatic cancer.
(Pink: FKBP12 ligand (HY-170988); Blue: E3 ligase ligand; Black: linker (HY-W004640)).
For research use only. We do not sell to patients.
- CAS No.: 2765058-89-5
- Formula: C59H76Cl2N4O13
- Molecular Weight:1120.16
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All PROTACs Isoforms
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Biological Activity
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FKBP12 |
10-SLF (0.1-5 μM; 2-24 h) selectively promotes proteasome- and Cullin-RING ligase-dependent degradation of FLAG-FKBP12_NLS in HA-FBXW7R465C-expressing HEK293T cells, with maximal degradation observed after 8 h of 1 μM treatment[1].
10-SLF (1 μM) induces UPS-dependent ubiquitination of FKBP12 exclusively in HA-FBXW7R465C-expressing HEK293T cells, as measured by a significant increase in normalized NanoBRET ratio (*P < 0.001)[1].
10-SLF (1 μM) induces UPS-dependent engagement of FKBP12 with the proteasomal subunit PSMD3 exclusively in HA-FBXW7R465C-expressing HEK293T cells, as measured by a significant increase in normalized NanoBRET ratio[1].
10-SLF (5 μM) induces degradation of FLAG-FKBP12_NLS in parental FBXW7R465C-expressing AsPC-1 cells, but not in FBXW7R465C KO AsPC-1 cells, demonstrating dependence on endogenous FBXW7R465C[1].
10-SLF (2 μM) promotes formation of a ternary complex between FLAG-FKBP12_NLS and FBXW7 variants containing the KRASG12C-like FBXW7R465C mutation (FBXW7R465C and FBXW7R465C/C466A) in HEK293T cells, but not with FBXW7 WT or FBXW7C466A[1].
10-SLF (0.01-10 μM) induces a dose-dependent interaction between FKBP12 and FBXW7R465C in HEK293T cells (with a hook effect at 5 and 10 μM), but does not induce interaction with FBXW7 WT[1].
10-SLF (1 μM) engages 8 off-target cysteines (≥50% engagement) in HA-FBXW7-R465C-expressing HEK293T cells, while the target FBXW7-R465C peptide was not detected in the assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293T cells expressing FBXW7-R465C and FLAG-FKBP12_NLS
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Concentration:0.1-5 μM
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Incubation Time:2-24 h
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Result:Selectively induced the targeted degradation of FKBP12.
Induced target protein degradation in a dose-dependent manner, exhibiting degradation activity starting at the 0.25 μM concentration.
Progressively induced target protein degradation over time and reached the maximum degradation level after 8 hours of treatment.
10-SLF-mediated targeted protein degradation effect was blocked by the proteasome inhibitor MG132 (HY-13259), the ligand SLF (HY-114872), and the neddylation inhibitor MLN4924 (HY-70062).
Chemical Information
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CAS No. 2765058-89-5
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Molecular Weight 1120.16
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Formula C59H76Cl2N4O13
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SMILES
O=C([C@H]1N(CCCC1)C(C(C(C)(C)CC)=O)=O)O[C@H](CCC2=CC(OC)=C(C=C2)OC)C3=CC=CC(OCC(NCCCOCCOCCOCCCN(C(CCl)=O)C(C4=CC=C(C=C4)Cl)C(NCC5=CC=CC=C5)=O)=O)=C3
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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)