glue

N-Boc-4-pentyne-1-amine is an alkyl chain-based PROTAC linker compound used in the synthesis of PROTAC MG-277 [1].

Mezigdomide (CC-92480) is a potent, novel, selective and active cereblon E3 ubiquitin ligase modulator (CELMoD) that acts as a molecular glue. Mezigdomide has anti-myeloma activity. [1]

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).

MG-277 is a molecular glue compound transformed from PROTAC degradation agent, MG-277 potently inhibits tumor cell growth in a p53-independent manner.

(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-JQ1 is a potent and specific proteolysis targeting chimera (PROTAC) that specifically degrades BRD4, acting as a molecular glue. It does not degrade BRD2 or BRD3. The mechanism of action involves covalent modification of the E3 ligase DCAF16, thereby promoting BRD4 degradation. Importantly, KB02-JQ1 demonstrates enhanced stability and durability in facilitating protein degradation within biological systems. The compound forms a complex with the ubiquitin E3 ligase ligand KB02 through a linker, resulting in the formation of KB02-JQ1[1].

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.

QS-57 is a PROTAC that targets BRD4 and can also function as a molecular glue for 14-3-3.

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.

GR-14-3-3 stabilizer-1 (compound 10) is a molecular glue stabilizer designed for the creation of a molecular adhesive that targets glucocorticoid receptors (GR), thereby inhibiting the interaction between GR and 14-3-3 proteins.

ChREBPα 14-3-3 regulator-1 (Compound 43) is a selective molecular glue that stabilizes the interaction between carbohydrate response element-binding protein (ChREBP) and 14-3-3 proteins, with an EC50 of 3.8 μM. It effectively safeguards β cells from glucolipotoxicity, preserving cell function and making it relevant for type 2 diabetes research.

IPS-06061 is an orally active molecular glue that forms a ternary complex with CRBN and KRASG12D, capable of degrading KRAS G12D, with a DC50 of less than 500 nM.

HGC652 is a molecular glue that targets the E3 ubiquitin ligase TRIM21, facilitating the formation of a ternary complex between TRIM21 and NUP98, which induces the degradation of NUP155 and nuclear pore complex proteins, ultimately leading to cell death. HGC652 inhibits the proliferation of various cancer cells, with its antiproliferative activity depending on the expression level of TRIM21.

CQ627 is a molecular glue that targets the degradation of RIOK2. It effectively recruits the E3 ubiquitin ligase RNF126, inducing the proteasomal degradation of RIOK2 via the ubiquitin-proteasome system (UPS) in MOLT4 leukemia cell lines, with a DC50 value of 410 nM. Additionally, CQ627 induces apoptosis in a dose-dependent manner in these cells, blocking the cell cycle at the G2 M phase, and exhibits antiproliferative activity across various cancer cell lines. It also demonstrates in vivo anticancer activity in MOLT4 xenograft mouse models.

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.

XYD049 (compound 7d) is a CRBN-type molecular glue targeting GSPT1, with a DC50 of 19 nM, used for researching MYC-driven castration-resistant prostate cancer (CRPC). It effectively inhibits the growth of 22Rv1 cells (IC50 = 7 nM) and exhibits antitumor efficacy in vivo. XYD049 downregulates CRPC-associated oncogenes in 22Rv1 cells, including AR, AR-v7, PSA, and c-Myc. XYD049 comprises a molecular glue linker (black part) NH2-C5-NH-Boc, a CRBN-type E3 ligase ligand (blue part) Thalidomide 4-fluoride, and a target protein ligand (red part) GSPT1 ligand-1, with the E3 ligase ligand + linker forming the conjugate E3 Ligase Ligand-linker Conjugate 158.

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.

MNN-02-155 is a bivalent molecular glue that can simultaneously interact with both p300/CBP and BCL6. It effectively induces the activation of BCL6-targeted reporter genes and promotes cell death. This compound is used in the research of diffuse large B-cell lymphoma (DLBCL).

TCIP3 is a bivalent molecular glue (molecular glue) that can simultaneously bind to both p300/CBP and BCL6. It redirects p300 and CBP to activate programmed cell death genes, which are typically repressed by the oncogenic driver BCL6. TCIP3 is useful for studying diffuse large B-cell lymphoma (DLBCL) and is not toxic to untransformed tonsil lymphocytes or fibroblasts.

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.