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.

VAV1 degrader-3 is an orally active and efficient VAV1 molecular glue degrader that reduces immune cell activation, proliferation, and cytokine production, useful for studying inflammation and autoimmune diseases.

VAV1 degrader-2 (Example 176) is a molecular gel degrader (DC50=4.41 nM) that targets VAV 1 for the study of inflammatory and autoimmune diseases.

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).

BMS-986449 is an IKZF2 (Helios)/IKZF4 (Eos) degrader and CELMoD molecular glue. It redirects the interaction between the E3 ubiquitin ligase Cereblon and Helios/Eos in primary Treg cells, inducing their degradation, and may be utilised for anti-tumour immunotherapy.

(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.

EM12-FS is a cereblon (CRBN) ligand that binds to CRBN at His353 and acts as a molecular glue degrader of NTAQ1. It has a half-life of 196 minutes in human plasma.

FIZ1 degrader 1 (compound 1) is an IMiD-based molecular glue degrader targeting FIZ1.

dCK1α-2 is an orally effective CK1α molecular glue (Molecular Glue) degrader that targets p53 pathway-related targets. It demonstrates antitumor efficacy in mouse models by enhancing the expression of p53-related genes.

WB214 is an MDM2 degrader (IC50 = 1.2 nM). Identified as the most potent antiproliferative agent in various leukemia cell lines, WB214 not only effectively promotes MDM2 degradation but also results in p53 degradation. Further studies demonstrate that WB214 acts as a molecular glue to degrade MDM2. It was ultimately discovered that WB214 efficiently degrades GSPT1, which helps to elucidate its mechanism of cell growth inhibition.

WIZ degrader 8 (compound 10) is a potent and selective molecular glue degrader of the transcription factor WIZ, effectively inducing HbF expression. It promotes WIZ degradation and HbF induction, suggesting its potential use as an inhibitor for sickle cell disease.

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.

LC-04-045 is a molecular glue degrader (MGD) of NEK7 (NIMA related kinase 7). This compound effectively degrades NEK7 in MOLT-4 cells, exhibiting a DC50 (half-maximal degradation concentration) of 7 nM and a Dmax (maximum degradation rate) of 90%. LC-04-045 displays high selectivity for NEK7 across the proteome and mediates NEK7 degradation via the ubiquitin-proteasome system (UPS), relying on a degradation motif that includes glycine 57 (G57) in NEK7. Additionally, LC-04-045 effectively inhibits the secretion of IL-1β and IL-18, with IC50 values of 33.03 nM and 32.99 nM, respectively. LC-04-045 is applicable for research in inflammatory diseases.

NK7-902 is a CRBN molecular glue degrader of NEK7. It fully degrades NEK7 in human primary monocytes and whole blood, yet only partially inhibits NLRP3-dependent IL-1β production. NK7-902 results in profound and lasting degradation of NEK7, but only temporarily blocks NLRP3 inflammasome activation in non-human primates via oral administration. The compound demonstrates activity in mouse systems.

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.

BTX-7312 is a cereblon-based SOS1 bifunctional degrader and acts as a molecular glue (molecular glue). It reduces downstream signaling markers pERK and pS6 and demonstrates antiproliferative activity in cells with various KRAS mutations.