SMD-3236

SMD-3236 is a SMARCA2-targeted PRAOTAC degrader designed based on SMARCA ligands and VHL-1 ligands, with long-lasting antitumor activity in vivo. SMARCA2 is a synthetic lethal target in SMARCA4-deficient cancer cells, and SMD-3236 has a 2000-fold selectivity for degradation of SMARCA2 over SMARCA4, with a DC50max>95%. SMD-3236 can induce SMARCA2 loss in tumor tissues while retaining SMARCA4 protein, and inhibit tumor growth in the H838 smarca4-deficient human cancer xenograft model. SMD-3236 is composed of target protein ligand (red part) SMI-1074 (HY-170817), PROTAC linker (black part) (trans-4-Ethynylcyclohexyl) methyl methanesulfonate (HY-170825), and E3 ligase ligand (blue part) SMARCA2 ligand-14 (HY-170826), of which the E3 ligase ligand and linker form a conjugate E3 Ligase Ligand-linker Conjugate 159 (HY-170827) [1].

Product Specifications

CAS Number

[3033586-31-8]

UNSPSC

12352005

Target

Epigenetic Reader Domain; PROTACs

Related Pathways

Epigenetics; PROTAC

Applications

Cancer-programmed cell death

Field of Research

Cancer

Smiles

ClC1=CC=CC(N(C(C=C(C2CCN(C[C@H]3CC[C@H](C4=CN([C@@H](C(C)(C)C)C(N5[C@H](C(N[C@@H](CN6CCOCC6)C7=CC=C(C8=C(C)N=CS8)C=C7)=O)C[C@@H](O)C5)=O)N=N4)CC3)CC2)C=C9)=C9C%10%11CCCCC%11)C%10=N%12)=C1C%12=O

Molecular Formula

C61H75ClN10O5S

Molecular Weight

1095.83

References & Citations

[1]Yang L, et al. Discovery of SMD-3236: A Potent, Highly Selective and Efficacious SMARCA2 Degrader for the Treatment of SMARC4-Deficient Human Cancers. J Med Chem. 2025 Jan 23;68 (2) :1155-1178.