(R)-CR8 (CR8), a second-generation derivative of Roscovitine, is a highly effective inhibitor of CDK1/2/5/7/9. It exhibits inhibitory activity against CDK1/cyclin B (IC50=0.09 μM), CDK2/cyclin A (0.072 μM), CDK2/cyclin E (0.041 μM), CDK5/p25 (0.11 μM), CDK7/cyclin H (1.1 μM), CDK9/cyclin T (0.18 μM), and CK1δ/ε (0.4 μM). (R)-CR8 induces apoptosis and demonstrates neuroprotective properties. Additionally, it functions as a molecular glue degrader, specifically targeting and depleting cyclin K.

MMH2 is a novel BRD4 molecular glue degrader that operates by recruiting the CUL4 and DCAF16 ligases to the second bromodomain of BRD4 (BRD4BD2).

MMH1 is a first-in-class molecular glue degrader that specifically targets the second bromodomain of BRD4 (BRD4BD2) through an innovative mechanism of action. By simultaneously engaging both BRD4BD2 and the CUL4-DCAF16 E3 ubiquitin ligase complex, MMH1 induces targeted protein degradation with exceptional specificity.

TMX1 is a covalent molecular glue degrader targeting BRD4. It selectively recruits DCAF16 to the BRD4BD2 domain, resulting in the degradation of BRD4.

HQ461 is a molecular glue degrader that facilitates the interaction between CDK12 and the DDB1-CUL4-RBX1 E3 ubiquitin ligase, resulting in the polyubiquitination and subsequent degradation of the CDK12-interacting protein Cyclin K (CCNK). This degradation impairs CDK12 function, leading to reduced phosphorylation of its substrates, downregulation of DNA damage response genes, and ultimately, cell death.

EN450 is a cysteine-reactive covalent molecular glue degrader specifically designed to target NF-κB.

HQ005 is a highly efficient molecular glue degrader that induces the selective degradation of ​Cyclin K (CCNK) with exceptional potency (DC50 = 41 nM). By facilitating novel protein-protein interactions between ​CCNK and the ​ubiquitin-proteasome system, HQ005 promotes targeted ubiquitination and proteasomal clearance of CCNK, offering a precise pharmacological tool for modulating ​CDK12/13-dependent transcription and ​DNA damage response pathways.

dCeMM2 (Compound 2) is a molecular glue degrader that drives the ubiquitination and degradation of cyclin K. It achieves this by facilitating an interaction between the CDK12-cyclin K complex and the CRL4B ligase complex.

WBC100 (14-D-Valine-TPL) is a potent, selective, and orally active molecular glue degrader targeting c-Myc. It facilitates the degradation of c-Myc through the ubiquitin E3 ligase CHIP-mediated 26S proteasome pathway. WBC100 is specifically utilized for research involving c-Myc overexpressing tumors.

dCeMM1 is a molecular glue degrader targeting RBM39. It functions by redirecting the activity of the CRL4DCAF15 ligase, leading to a reduction in RBM39 levels in WT KBM7 cells.

MGD-28 is a potent molecular glue degrader that demonstrates significant in vitro efficacy against various hematological cancer cell lines. It induces degradation of Ikaros family zinc finger proteins 1, 2, and 3 (IKZF1/2/3) and casein kinase 1 alpha (CK1α) with nanomolar potency via a Cullin-cereblon (CRBN) dependent pathway. Compared to lenalidomide and pomalidomide, MGD-28 achieves deeper, faster, and more potent degradation of these neosubstrates. Additionally, MGD-28 exhibits broad antiproliferative activity in multiple solid malignancies and shows preferential cytotoxicity toward multiple myeloma patient-derived cells at various disease stages.

dWIZ-1 is a first-in-class molecular glue degrader that specifically targets the WIZ transcription factor for proteasomal degradation, leading to potent induction of fetal hemoglobin (HbF) in erythroblasts. This novel compound functions by enhancing the interaction between CRBN and WIZ, demonstrating an EC50 of 547 nM for CRBN-WIZ complex formation.

dCeMM3 (Compound 3) is a molecular glue degrader that facilitates the ubiquitination and degradation of cyclin K. It achieves this by promoting an interaction between the CDK12-cyclin K complex and the CRL4B ligase complex.

MG-277, a molecular glue degrader, efficiently induces the degradation of the translation termination factor GSPT1, based on the Cereblon E3 ligand, with a DC50 of 1.3 nM. It potently inhibits tumor cell growth in a p53-independent manner, demonstrating IC50 values of 3.5 nM for RS4;11 cells and 3.4 nM for p53 mutant RS4;11/IRMI-2 cells. MG-277 exhibits significant anticancer activity.

SJ3149 is a highly selective and potent molecular glue degrader targeting CK1α protein, exhibiting broad antiproliferative activity. It is a valuable tool for cancer research.

dCeMM4 (Compound 5) is a molecular glue degrader that facilitates the ubiquitination and degradation of cyclin K. It achieves this by promoting an interaction between the CDK12-cyclin K complex and the CRL4B ligase complex.

dWIZ-2 is a molecular glue degrader of the WIZ transcription factor that robustly induce HbF in erythroblasts. dWIZ-2 shows improved pharmacokinetic (PK) properties than dWIZ-1.

MRT-6160 represents a groundbreaking molecular glue degrader designed to selectively target VAV1, achieving its proteasomal degradation with a DC50 value of 7 nM. This innovative compound showcases its unique mechanism and therapeutic potential.

DS17 is a high-efficiency molecular glue degrader that specifically induces the degradation of cyclin K, demonstrating remarkable potency with an EC50 of 13 nM. By exploiting the ubiquitin-proteasome system, DS17 effectively eliminates cyclin K, a critical regulator of transcription and cell cycle progression, positioning it as a valuable tool in cancer research and drug discovery.

ALV1 is a molecular glue degrader targeting Ikaros (IKZF1) and Helios (IKZF2), with DC50 values of 2.5 nM and 10.3 nM, respectively. It binds to CRBN with an IC50 of 0.55 µM and induces CRBN-Helios dimerization. ALV1 is a valuable tool for studying the properties and functions of regulatory T cells (Treg cells).

ZZ3 is a potent CDK12/13 molecular glue degrader with DC50 of 35 nM and 57 nM, respectively.

KT-333 is a first-in-class molecular glue that induces ​selective degradation of STAT3 via the ubiquitin-proteasome system by simultaneously engaging ​STAT3 and the VHL E3 ligase. This novel mechanism enables potent ​STAT3 depletion with minimal off-target effects, demonstrating strong ​anti-tumor activity in hematologic malignancies.

IKZF1-degrader-1 (Compound 9-B) is a highly potent molecular glue that achieves sub-nanomolar degradation of IKZF1 (DC50 = 0.134 nM), demonstrating significant therapeutic potential for targeting IKZF1-dependent malignancies.

EN171 covalently targets both C38 and C96 on 14−3−3 to enhance 14−3−3 interactions with ERα, YAP, and TAZ, leading to impaired estrogen receptor and Hippo pathway transcriptional activity.

EM12-FS is a bifunctional CRBN modulator that engages cereblon at His353 while functioning as a molecular glue to induce NTAQ1 degradation. Demonstrating favorable pharmacokinetics, it exhibits a human plasma half-life of 196 minutes, supporting its therapeutic potential.

Acetyl-cyclosporin A aldehyde is a chemically modified derivative of cyclosporin A (HY-B0579), featuring an acetyl group and a reactive aldehyde moiety. The parent compound, cyclosporin A, is a dual-function molecule that both inhibits calmodulin signaling and binds cyclophilin, thereby blocking NF-AT nuclear translocation and inducing mitochondrial dysfunction.

QS-57 is a bifunctional degrader that combines BRD4-targeting PROTAC activity with 14-3-3 molecular glue properties.