glue degrader

dCeMM3 (2-(1H-benzimidazol-2-ylsulfanyl)-N-(5-chloropyridin-2-yl)acetamide) is a glue degrader. dCeMM3 prompts an interaction of CDK12-cyclin K with a CRL4B ligase complex, result in inducing ubiquitination and degradation of cyclin K.

dCeMM1, a RBM39 glue degrader, re-directs the activity of the CRL4DCAF15 ligase and decreases RBM39 expression levels in WT KBM7 cells.

dWIZ-1 ((rac)-dWIZ-1) is a potent WIZ molecular gel degrader that recruits WIZ (ZF7) to the cereblon thereby inducing degradation and thus induction of haemoglobin fetalis (HbF) in erythroblasts, which can be used to study sickle cell disease (SCD).

(R)-CR8 trihydrochloride (CR8, (R)-Isomer trihydrochloride) is a CDK1/2/5/7/9 inhibitor that acts as a molecular glue degrader with neuroprotective activity and induces apoptosis.

KB02-SLF is a PROTAC-based nuclear FKBP12 degrader, also known as a molecular glue, that facilitates the degradation of nuclear FKBP12 by covalently modifying DCAF16, an E3 ligase. SLF acts as a linker, binding to the ubiquitin E3 ligase ligand KB02, thus forming KB02-SLF[1] and enhancing the longevity of protein degradation in biological systems.

SJ46411-Br is an orally effective CK1α molecular glue (Molecular Glue) degrader. It binds with CRL2^KLHDC2 to facilitate the formation of a cooperative homoselective ternary complex. Furthermore, SJ46411-Br is coupled with the BET ligand JQ1 through a PROTAC linker, enabling the synthesis of corresponding PROTACs.

QXG-6442 is a molecular glue degrader targeting CK1α, demonstrating a degradation potency with a DC50 of 5.7 nM and a Dmax of 90%. In the MOLM-14 cell line, QXG-6442 induces antiproliferative effects.

AMPTX-1 is a molecular glue functioning as a potent, selective, and reversible covalent degrader of BRD9 by recruiting it to the E3 ligase DCAF16.

dGEM3 is a molecular glue degrader targeting GEMIN3 (a component of the survival of motor neuron complex). It is applicable in research on diseases related to abnormal protein regulation, such as cancer and neurodegenerative disorders.

KMG-1068 (Compound 4a), a molecular glue, acts as a GSPT1/2 degrader. By binding to the IMiD binding site on CRBN, KMG-1068 efficiently induces CRBN-dependent degradation of GSPT1/2 and facilitates the formation of a ternary complex with GSPT1/2. KMG-1068 holds potential for use in cancer research.

(S)-dHTC1 is a molecular glue degrader specifically targeting the transcriptional coactivator ENL. It exhibits high affinity binding to E3 ligase only upon formation of the ENL:(S)-dHTC1 complex, with an IC50 of 93 nM. In MV4;11 cells, (S)-dHTC1 degrades ENL with a DC50 of 26 nM. This compound can be utilized for acute myeloid leukemia research.

BWA-6047 is a dual AR/AR-V7 and GSPT1 PROTAC-type degrader (AR: DC50= 3.7 nM; AR-V7: DC50= 3.0 nM; GSPT1: DC50= 1.2 nM). It facilitates the ubiquitination and degradation of AR/AR-V7 and, through molecular glue properties, induces a PPI between GSPT1 and CRBN, leading to GSPT1 degradation. BWA-6047 is applicable in prostate cancer research.

IKZF2-degrader 1 (Compound 31) is a molecular glue-type degrader of IKZF2 with a DC50 of 0.5 nM. It exhibits relatively low degradation activity against CK1α, with a DC50 of 210 nM. This compound is applicable in research focused on IKZF2-dependent cancers.

dCeMM4 (Compound 5) is a glue degrader that promotes cyclin K ubiquitination and degradation by facilitating the interaction between CDK12-cyclin K and a CRL4B ligase complex [1].

dCeMM2 is a glue degrader. dCeMM2 prompts an interaction of CDK12-cyclin K with a CRL4B ligase complex, leading to the ubiquitination and degradation of cyclin K.

WBC100 (14-D-Valine-TPL) is a potent, selective, orally active c-Myc glue degrader targeting the ubiquitin E3 ligase CHIP-mediated 26S proteasome pathway, primarily used in research for c-Myc overexpressing tumors [1].

GBD-9, a dual-mechanism degrader, effectively promotes the degradation of BTK and GSPT1 through recruitment of E3 ligase cereblon (CRBN). As a PROTAC molecule, GBD-9 induces BTK degradation, while also acting as a molecular glue for GSPT1 degradation, demonstrating potent inhibition of cancer cell growth [1].

PROTACGSPT1 degrader-2 (compound A) acts as a molecular glue for GSPT1, achieving degradation efficiencies exceeding 95%. Meanwhile, GSPT1 degrader-8 exhibits inhibitory effects on HL-60 cells, demonstrating an IC50 of 10 nM.

BRD9 Degrader-3 (compound B20) is a molecular glue for BRD9 with a DC50 of less than 1.25 nM.

JP-2-249, a molecular glue, serves as an effective degrader of SMARCA2. At concentrations ranging from 1-10 μM, JP-2-249 reduces the protein levels of SMARCA2 in MV-4-11 cells.

HQ461 is a molecular glue that promotes CDK12-DDB1 interaction, triggering cyclin K degradation, decreased CDK12 substrate phosphorylation, downregulation of DNA damage response genes, and cell death.