CARM1 degrader-1 hydrochloride 

CARM1 degrader-1 hydrochloride is a CARM1 PROTAC degrader (DC₅₀ = 8.1 nM) with high selectivity over other protein arginine methyltransferases. CARM1 degrader-1 hydrochloride degrades CARM1 in a VHL- and proteasome-dependent manner. CARM1 degrader-1 hydrochloride downregulates the methylation level of CARM1 substrates in cell-based assays. CARM1 degrader-1 hydrochloride inhibits cancer cell migration in cell-based assays. CARM1 degrader-1 hydrochloride can be used in breast cancer research^[1]. (Pink: CARM1 ligand (HY-114965); Blue: VHL ligand (HY-112078); Black: linker).

CARM1 degrader-1 (compound 3b) (6.25-500 nM, 0.1-10 μM; 1-48 h) hydrochloride potently degrades CARM1 in MCF7 cells with a DC₅₀ of 8.1 nM and 97% maximal degradation, achieving significant degradation within 2 h and sustaining it for up to 48 h^[1].
CARM1 degrader-1 (0.5 μM; 24 h) hydrochloride degrades CARM1 in MCF7 cells in a CARM1-binding-, VHL-, proteasome-, and neddylation-dependent manner^[1].
CARM1 degrader-1 (0.01-10 μM, 25 nM; 4-24 h) hydrochloride exerts highly selective degradation of CARM1 over PRMT1, PRMT6, and PRMT5 in MCF7 cells, with minimal off-target proteome effects^[1].
CARM1 degrader-1 (0.1-10 μM, 0.5 μM; 2-48 h) hydrochloride potently inhibits asymmetric dimethylation of CARM1 substrates BAF155 and PABP1 in MCF7, BT474, and MDA-MB-231 breast cancer cells, with at least 100-fold greater functional potency than the CARM1 inhibitor TP-064 in MCF7 cells^[1].
CARM1 degrader-1 (0.5 μM; 20 h) hydrochloride potently inhibits migration of MDA-MB-231 triple-negative breast cancer cells^[1].
CARM1 degrader-1 hydrochloride potently degrades CARM1 in MCF10A normal human mammary epithelial cells^[1].
CARM1 degrader-1 hydrochloride (7 days) does not inhibit proliferation of MCF7, MCF10A, or MDA-MB-231 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1316.14

C₇₁H₉₉ClN₁₂O₈S

Solid

Off-white to light yellow

O=C([C@H]1N(C([C@@H](NC(CN2CCN(CC3CCN(CC4CCN(C(COC5=CC=C(OC6=CC=CC(C(N(C)CC7=CC(C8CCN(CCNC)CC8)=NC=C7)=O)=C6)C=C5)=O)CC4)CC3)CC2)=O)C(C)(C)C)=O)C[C@H](O)C1)N[C@H](C9=CC=C(C%10=C(C)N=CS%10)C=C9)C.Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* 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.

• [1]. Xie H, et al. Development of Potent and Selective Coactivator-Associated Arginine Methyltransferase 1 (CARM1) Degraders. J Med Chem. 2023;66(18):13028-13042.  [Content Brief]