Molecular Glues Degrader

SJ6986 is a potent, selective and orally active GSPT1/2 Molecular Glue degrader, with a DC₅₀ of 2.1 nM (D_max 99%) for GSPT1.

NVS-VHL720 is a selective VHL-based cysteine dioxygenase (CDO1) molecular glue degrader. NVS-VHL720 recruits CDO1 to the VHL E3 ligase complex, driving ubiquitin-dependent proteasomal degradation of CDO1. NVS-VHL720 can be used for the research of cancer.

MMH2 is a novel BRD4 molecular glue degrader that functions by recruiting the CUL4 and DCAF16 ligases to the second bromodomain of BRD4 (BRD4_BD2).

HQ005 is a potent CCNK degrader with an DC₅₀ value of 0.041 µM. HQ005 is a molecular-glue degrader that mediates interactions between target proteins and components of the ubiquitin-proteasome system to cause selective protein degradation.

MMH1 is a novel BRD4 molecular glue degrader that functions by recruiting the CUL4 and DCAF16 ligases to the second bromodomain of BRD4 (BRD4_BD2).

LYG-409 is an orally active degrader of GSPT1. LYG-409 shows excellent anti-acute myeloid leukemia and prostate cancer in vivo with TGI of 94.34% and 104.49%, respectively. LYG-409 inhibits KG-1 cells mediated by the degradation of GSPT1 with an IC₅₀ of 9.50 nM, with a DC₅₀ of 7.87 nM in vitro.

PVTX-405 is a selective and oral active IKZF2 molecular glue degrader with a DC₅₀  of  0.7 nM and a D_max of 91%. PVTX-405 enhances degradation efficiency, significantly reduces off-target degradation, and alleviates hERG inhibition with IC₅₀ of 48 µM. PVTX-405 significantly inhibits the growth of MC38 tumors, with greater synergistic anti-cancer efficacy in combination with immune checkpoint therapies (ICTs) (anti-PD1 or anti-LAG3) in the MC38 mouse tumor xenograft model using Crbn^391V C57BL/6 mice.

dWIZ-1 is an orally active molecular glue and chemical probe targeting the WIZ transcription factor, which based on an IMiD backbone, binding to human WIZ with an affinity of 3.5 μM. dWIZ-1 recruits WIZ to the cereblon-DDB1 complex via its ZF7 domain, thereby triggering proteasome-dependent degradation of WIZ. dWIZ-1 significantly induces fetal hemoglobin expression in erythroblasts while reducing the level of inhibitory H3K9 dimethylation at WIZ binding sites such as the β-globin locus. Meanwhile, dWIZ-1 does not affect the proliferation and differentiation of erythroblasts, and no cytotoxicity is observed in in vitro cells or cynomolgus monkey models. dWIZ-1 serves as a critical tool molecule for investigating the mechanism and underlying pathways of sickle cell disease.

INNO-220 is an orally active, CRBN-dependent molecular glue degrader targeting CK1α. INNO-220 induces cell cycle arrest at G0/G1 phase and triggers apoptosis by degrading CK1α. INNO-220 disrupts the assembly and function of the CARD11/BCL10/MALT1 complex, thereby inhibiting NF-κB signaling in stimulated T cells and lymphoma cells that harbor an activating mutation in CARD11. INNO-220 provides a new direction for lymphoma research.

PROTAC(H-PGDS)-7 is a Hematopoietic prostaglandin D synthase (H-PGDS) molecular glue degrader, with a DC₅₀ of 17.3 pM.

QXG-6442 is a CK1α Molecular Glue Degrader. QXG-6442 exhibits CK1α degradation potency with a DC₅₀ of 5.7 nM and a D_max of 90%. QXG-6442 induces antiproliferative effects in MOLM-14 cell line.

UNC10088 is a molecular glue targeting NSD2. UNC10088 mediates the formation of a stable ternary complex between SCFFBXO22 and the NSD2 PWWP1 domain. UNC10088 promotes ubiquitination of the SCFFBXO22-dependent NSD2 PWWP1 domain through reversible covalent bonding with the C326 region of FBXO22. UNC10088 could be used in cancer research.

GSPT1 degrader-4 (3) is a GSPT1 molecule glue (DC₅₀ of 25.4 nM), with an IC₅₀ of 39 nM for CAL51 proliferation.

GSPT1 degrader-8 is a potent and orally active G1 to S phase transition 1 (GSPT1) molecular glue degrader. GSPT1 degrader-8 induces GSPT1 degradation and inhibits tumor growth. GSPT1 degrader-8 can be used for the research of cancer, such as breast cancer.

GSPT1 degrader-2 (Compound 210) is a potent and orally active GSPT1 molecular glue degrader (DC₅₀: < 30 nM). GSPT1 degrader-2 is an antitumor agent.

MG degrader 2 (Compound CM-2) is a CRBN-dependent molecular glue degrader. MG degrader 2 induces ZFP91, FIZ1 and PI4KB degradation. MG degrader 2 has anti-proliferative activity against MM.1S cells (IC₅₀ = 162 nM). MG degrader 2 can be used for the research of cancer, such as multiple myeloma.

BRD9 Degrader-3 (compound B20) is a BRD9 molecular glue, with a DC₅₀ of <1.25 nM.

AR Degrader-3 is an orally active molecular glue that targets AR/ARV7 and induces the degradation of AR and ARV7 through the ubiquitin-proteasome pathway (UPP). AR Degrader-3 directly interacts with the ligand-binding domain (LBD) and the N-terminal domain (NTD) of AR. AR Degrader-3 effectively suppresses the transcriptional activity of wild-type AR (AR-WT), AR mutants, and ARV7. AR Degrader-3 downregulates the mRNA and protein levels of downstream AR target genes, thereby overcoming antiandrogen resistance mediated by ARV7 and AR point mutations. AR Degrader-3 induces apoptosis in Enzalutamide (HY-70002) (ENZa)-resistant cells and increases cleaved caspase-3 protein levels. AR Degrader-3 can be used for the study of castration-resistant prostate cancer (CRPC).

GSPT1 degrader-11 is a CRBN-dependent G1 to S phase transition 1 (GSPT1) molecular glue degrader (DC₅₀ = 67.7 nM, D_max = 97%). GSPT1 degrader-11 can inhibit MDA-MB-231 CRBN-WT cells proliferation (IC₅₀ = 2.07 μM). GSPT1 degrader-11 can be used for the research of cancer.

SR-5037 is an orally active CDK12 (IC₅₀ = 31 nM)/CDK13 inhibitor and CycK (DC₅₀ = 30 nM; D_max > 98%) molecular glue degrader. SR-5037 inhibits the enzymatic activity of CDK12/CycK and CDK13/CycK complexes. SR-5037 promotes the recruitment of DDB1 to the CDK12/CycK complex, thereby triggering proteasome-mediated CycK degradation. SR-5037 degrades active CycK in mouse models of triple-negative breast cancer. SR-5037 can be used in the research of cancers such as triple-negative breast cancer.