Truly-4
Truly-4 is a bifunctional Rpn13 PROTAC and CRBN ByeTAC degrader. Degradation of Rpn13 relies on CRBN-mediated E3 ubiquitin ligase activity, while degradation of CRBN itself proceeds via a ByeTAC mechanism of action. Truly-4 induces selective cytotoxicity in hematological cancer cells and solid cancer cells, but not in healthy cells, despite comparable levels of Rpn13 depletion in both cell types. Truly-4 can be used in studies related to B-cell lymphoma and triple-negative breast cancer.
(Pink: Rpn13 ligand (HY-159808); Blue: Cereblon ligand (HY-139539); Black: linker (HY-W008352)).
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- Formule: C43H44BrClN8O10S
- Masse moléculaire:980.28
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Stockage:
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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Activité biologique
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Cereblon |
Truly-4 (0.5-10 μM; 18 h) induces concentration-dependent degradation of CRBN (via E-ligase-independent ByeTAC mechanism) and Rpn13 (via ubiquitin-dependent PROTAC mechanism) in Ramos B-cell lymphoma cells, with 10 μM treatment reducing CRBN to 48% and Rpn13 to 35% of baseline levels after 18 h[1].
Truly-4 (0.5-10 μM; 18 h) induces concentration-dependent degradation of CRBN and Rpn13 in MDA-MB-468 triple-negative breast cancer cells, with 10 μM treatment reducing CRBN to 56% and Rpn13 to 39% of baseline levels after 18 h[1].
Truly-4 (0.001-100 μM; 48 h) induces selective cytotoxicity in Ramos B-cell lymphoma and MDA-MB-468 triple-negative breast cancer cells after 48 h incubation, with no significant toxicity observed in HEK-293T or MRC-5 nonmalignant cells[1].
Truly-4 (0.5-10 μM; 18 h) induces concentration-dependent degradation of Rpn13 but does not degrade CRBN in HEK-293T nonmalignant cells, with CRBN levels remaining stable or slightly elevated[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Ramos B-cell lymphoma suspension cells
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Concentration:0.5, 1 and 10 μM (18 h incubation); 10 μM (18 h incubation with co-reagents); 25 μM (2 h co-immunoprecipitation; 18 h incubation with pre-treatment reagents); 10 μM (4, 8, 48 h time-course)
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Incubation Time:18 h (0.5-10 μM; 10 μM with co-reagents; 25 μM with pre-treatment reagents); 2 h (25 μM co-immunoprecipitation); 4, 8, 48 h (10 μM time-course)
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Result:Reduced CRBN levels to 88% and Rpn13 levels to 76% of baseline at 0.5 μM.
Reduced CRBN to 52% and Rpn13 to 60% of baseline at 1 μM.
Reduced CRBN to 48% and Rpn13 to 35% of baseline at 10 μM.
Fully abrogated degradation of both CRBN and Rpn13 when co-treated with 20 nM proteasome inhibitor MG-132.
Rescued Rpn13 degradation but did not affect CRBN degradation when co-treated with 10 nM ubiquitin-activating enzyme inhibitor TAK-243 or 10 nM NEDD8-activating enzyme inhibitor MLN4924.
Increased ubiquitinated Rpn13 levels by 51% relative to control at 25 μM.
Blocked CRBN degradation but modestly enhanced Rpn13 degradation when pre-treated with 25 μM Rpn2 peptide.
Attenuated degradation of both proteins when pre-treated with 25 μM TCL1 or immunomodulatory imide drug thalidomide.
Induced rapid and sustained degradation of both proteins over 48 h in time-course experiments.
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Cell Line:MDA-MB-468 triple-negative breast cancer adherent cells
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Concentration:0.5, 1 and 10 μM
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Incubation Time:18 h
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Result:Reduced CRBN levels to 72% and Rpn13 levels to 61% of baseline at 0.5 μM.
Reduced CRBN to 65% and Rpn13 to 64% of baseline at 1 μM.
Reduced CRBN to 56% and Rpn13 to 39% of baseline at 10 μM.
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Cell Line:HEK-293T nonmalignant adherent cells
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Concentration:0.5, 1 and 10 μM
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Incubation Time:18 h
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Result:Reduced Rpn13 levels to 71% of baseline (CRBN levels remained at 100%) at 0.5 μM.
Reduced Rpn13 to 51% of baseline (CRBN levels increased to 117%) at 1 μM.
Reduced Rpn13 to 49% of baseline (CRBN levels increased to 112%) at 10 μM.
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Cell Line:Ramos B-cell lymphoma, MDA-MB-468 triple-negative breast cancer, HEK-293T nonmalignant, MRC-5 nonmalignant fibroblast cells
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Concentration:0.001, 0.1, 1, 10 and 100 μM
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Incubation Time:48 h
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Result:Induced potent cytotoxicity in Ramos and MDA-MB-468 cancer cells, with viability dropping to near 0% at 100 μM.
Caused no measurable loss of viability in HEK-293T and MRC-5 nonmalignant cells even at the highest concentration tested.
Chemical Information
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Masse moléculaire 980.28
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Formule C43H44BrClN8O10S
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SMILES
O=C(NCCOCCOCCOCCOCCNC(C1=CC2=C(C(N(C2=O)C3CCC(NC3=O)=O)=O)C=C1)=O)CC4SC5=NN=C(N5N=C4C6=CC=C(C=C6)Cl)CC7=CC=C(C=C7)Br
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Truly-4 Related Classifications
HY-187439 Related Classifications
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