PROTAC PRMT1 degrader-1
PROTAC PRMT1 degrader-1 (compound 4) is a PRMT1 PROTAC degrader, with a DC50 of 0.77 μM (MCF-7 cells). PROTAC PRMT1 degrader-1 recruits the CRBN E3 ubiquitin ligase to induce proteasome-dependent degradation of PRMT1; it also forms a ternary complex with PRMT1 and CRBN, promoting ubiquitination and subsequent proteasomal degradation of PRMT1. PROTAC PRMT1 degrader-1 reduces the level of asymmetric dimethylarginine in cancer cells, as well as the level of asymmetric dimethylation of arginine 3 on histone H4, while inhibiting the growth of various cancer cells. PROTAC PRMT1 degrader-1 can be used in the research of breast cancer and melanoma.
(Pink: PRMT1 ligand (HY-182297); Blue: Cereblon ligand (HY-14658); Black: linker (HY-133388)).
For research use only. We do not sell to patients.
- Formula: C43H56N6O6
- Molecular Weight:752.94
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
PROTAC PRMT1 degrader-1 (1 μM) inhibits purified PRMT1 methyltransferase activity with an 86.2% inhibition rate at 1 μM and an IC50 of 185.7 nM in AlphaLISA biochemical assays, while also inhibiting other type I PRMT enzymes in the same assay format[1].
PROTAC PRMT1 degrader-1 (0.1-5 μM; 3-96 h) induces concentration- and time-dependent degradation of PRMT1 in MCF-7 human breast cancer cells, with a DC50 of 0.77 μM, Dmax of 84.83%, and detectable degradation starting at 6 h post-treatment[1].
PROTAC PRMT1 degrader-1 (0.1-5 μM; 48 h) induces concentration-dependent degradation of PRMT1 in A2058 human melanoma cells, with a DC50 of 0.65 μM and a Dmax of 93.03%[1].
PROTAC PRMT1 degrader-1 (0.1-5 μM; 48 h) induces concentration-dependent degradation of PRMT1 in MDA-MB-231, MDA-MB-468, and A375 human cancer cells, with a DC50 of 0.52 μM and Dmax of 88.36% in A375 cells[1].
PROTAC PRMT1 degrader-1 (2 μM; 12-96 h) selectively degrades PRMT1 over PRMT3, PRMT4, PRMT6, and PRMT8 in MCF-7 human breast cancer cells, and does not degrade common CRBN neosubstrates GSPT1, IKZF1, or IKZF3[1].
PROTAC PRMT1 degrader-1 (2 μM; 12-96 h) reduces global asymmetric dimethylarginine levels and histone H4R3me2a levels in a time-dependent manner in MCF-7 human breast cancer cells[1].
PROTAC PRMT1 degrader-1 (1.25-5 μM; 5 days) exhibits dose-dependent growth inhibition of MCF-7 human breast cancer cells and A2058 human melanoma cells over 5 days, with stronger activity than the parental inhibitor DCPT2145, and greater sensitivity observed in A2058 cells[1].
PROTAC PRMT1 degrader-1 (0.63-10 μM; 14 days) inhibits colony formation of MCF-7 human breast cancer cells at 2.5 μM and above, and of A2058 human melanoma cells at 1.25 μM and above, with A2058 cells showing greater sensitivity[1].
PROTAC PRMT1 degrader-1 (1 μM; 0-60 min) has moderate metabolic stability in mouse liver microsomes, with a half-life of 26.0 min and an intrinsic clearance rate of 211 mL/min/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:MCF-7 human breast cancer cells
-
Concentration:0.1-5 μM (48 h concentration-dependent); 5 μM (time-course); 2 μM (time-course)
-
Incubation Time:3-96 h (time-course); 48 h (concentration-dependent)
-
Result:Reduced PRMT1 protein levels by 40%, 60%, and 86.5% respectively at 0.2, 1, 5 μM for 48 h.
Induced concentration-dependent PRMT1 degradation with a DC50 of 0.77 μM and a maximum degradation (Dₘₐₓ) of 84.83% at 0.1, 0.3, 0.5, 1, 3, 5 μM for 48 h.
Induced detectable PRMT1 degradation as early as 6 h, with near-maximal degradation observed at 48 h at 5 μM.
Caused significant PRMT1 degradation at 48 h, with maximum degradation achieved between 72-96 h at 2 μM.
-
Cell Line:A2058 human melanoma cells
-
Concentration:0.1-5 μM
-
Incubation Time:48 h
-
Result:Induced concentration-dependent PRMT1 degradation with a DC50 of 0.65 μM and a Dₘₐₓ of 93.03%.
-
Cell Line:MDA-MB-231, MDA-MB-468, A375 human cancer cells
-
Concentration:0.1-5 μM (A375 cells only)
-
Incubation Time:48 h (A375 cells only)
-
Result:Reduced PRMT1 protein levels in a concentration-dependent manner in MDA-MB-231 and MDA-MB-468 cells.
Induced concentration-dependent PRMT1 degradation with a DC50 of 0.52 μM and a Dₘₐₓ of 88.36% in A375 cells.
-
Cell Line:MCF-7 human breast cancer cells
-
Concentration:2 μM
-
Incubation Time:12-96 h
-
Result:Reduced PRMT1 protein levels in a time-dependent manner, but had no significant effect on PRMT3, PRMT4, or PRMT6 protein levels over 12-96 h, and only slightly reduced PRMT8 protein levels at 96 h.
Did not degrade CRBN neosubstrates GSPT1, IKZF1, or IKZF3 at these concentrations and time points.\nInduced a time-dependent reduction in global aDMA levels and asymmetric dimethylation of histone H4 arginine 3 (H4R3me2a) levels, consistent with PRMT1 degradation kinetics.
-
Cell Line:MCF-7 human breast cancer cells, A2058 human melanoma cells
-
Concentration:1.25-5 μM
-
Incubation Time:5 days
-
Result:Showed stronger dose-dependent growth inhibition than the parental inhibitor DCPT2145 at all tested concentrations over 5 days in MCF-7 cells.
Showed stronger dose-dependent growth inhibition than DCPT2145 at all tested concentrations over 5 days in A2058 cells, with greater sensitivity observed in A2058 cells compared to MCF-7 cells.
Chemical Information
-
Molecular Weight 752.94
-
Formula C43H56N6O6
-
SMILES
O=C1N(C(C2=C1C=CC=C2NCCCCCCCCCCCCNC(C3=CC=C(OC4=CC=CC=C4CN(C)CCNC)C=C3)=O)=O)C(C(N5)=O)CCC5=O
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
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)
Powered by Bioz