PROTAC CRBN Degrader-1 is a chemical compound consisting of a cereblon (CRBN) ligand binding group, a linker, and a von Hippel-Landau (VHL) binding group. It functions as a cereblon (CRBN) degrader[1].

Desmorpholinyl Navitoclax-NH-Me (Desmorpholinyl ABT-263-NH-Me) is a Bcl-xL inhibitor, which can be employed alongside a CRBN ligand to synthesize XZ739, a PROTAC BCL-XL degrader [1] [2].

SR-1114, a first-in-class PROTAC ENL degrader, induces rapid CRBN-dependent ENL degradation with DC50 values of 150 nM in MV4;11 cells, 311 nM in MOLM-13 cells, and 1.65 μM in OCI/AML-2 cells [1].

PROTAC Mcl1 degrader-1 induces the ubiquitination and proteasomal degradation of Mcl-1 by introducing the E3 ligase cereblon (CRBN)-binding ligand pomalidomide to Mcl-1 inhibitor S1-6 with μM-range affinity. PROTAC Mcl1 degrader-1, a proteolysis targeting chimera (PROTAC), is a potently and selectively Mcl-1 inhibitor with an IC50 of 0.78 μM.

LSN3106729 hydrochloride, the metabolite of Abemaciclib , is a CDK inhibitor with antitumor activity. LSN3106729 hydrochloride and a CRBN ligand have been used to design PROTAC CDK4/6 degrader[1]. [1]. Edward S. Kim, et al. Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non-Small Cell Lung Cancer: A Phase Ib Study. [2]. Nathanael Gray, et al. Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use. WO2017185031A1.

PROTAC KRAS G12C degrader-1, a cereblon-based degrader, promotes CRBN/KRAS G12C dimerization and facilitates the degradation of GFP-KRAS G12C in reporter cells [1].

K-Ras ligand-Linker Conjugate 6 is a chemical compound that combines a ligand for K-Ras recruiting moiety and a PROTAC linker. This compound can recruit E3 ligases, including VHL, CRBN, MDM2, and IAP. K-Ras ligand-Linker Conjugate 6 is particularly useful in the synthesis of PROTAC K-Ras Degrader-1, a highly effective K-Ras degrader that achieves ≥70% degradation efficacy in SW1573 cells[1].

PROTAC EGFR degrader 7 (compound 13b) is a potent, selective CRBN-recruiting agent targeting EGFR L858R/T790M mutations with a DC50 of 13.2 nM. It effectively inhibits proliferation in NCI–H1975 cells with an IC50 of 46.82 nM and significantly triggers apoptosis and G2/M phase arrest in these cells. Demonstrating antitumor efficacy, PROTAC EGFR degrader 7 holds promise for non-small cell lung cancer (NSCLC) research [1].

Homo-PROTAC cereblon degrader 1 is a highly potent and efficient cereblon (CRBN) degrader with only minimal effects on IKZF1 and IKZF3.

PROTAC CDK9 degrader-2 (compounds 11c) is a potent and selective CDK9 degrader based on PROTAC, with an IC50 of 17 μM in MCF-7 cell lines. Natural product Wogonin binds ubiquitin E3 ligase cereblon (CRBN) via a linker to form PROTAC[1].

PF15, a selective FLT3-ITD degrader, serves as a PROTAC (proteolysis targeting chimera) tethering ligands for FLT3 kinase and CRBN. It exhibits a degradation concentration 50 (DC50) of 76.7 nM and notably impedes the proliferation of FLT3-ITD-positive cells. PF15 also reduces phosphorylation levels of FLT3 and STAT5 and demonstrates efficacy in inhibiting tumor growth in mouse models, suggesting potential applications in leukemia research [1].

K-Ras ligand-Linker Conjugate 1 is a chemical compound that includes a ligand for K-Ras and a PROTAC linker, facilitating the recruitment of E3 ligases VHL, CRBN, MDM2, and IAP. It can be utilized in the synthesis of PROTAC K-Ras Degrader-1, a highly effective K-Ras degrader that achieves ≥70% degradation efficacy in SW1573 cells[1].

Thalidomide 4-fluoride (E3 ligase Ligand 4) (Cereblon ligand 4) is the Thalidomide-based Cereblon ligand. Thalidomide 4-fluoride can be used in the recruitment of CRBN protein. Thalidomide 4-fluoride (Cereblon ligand 4) can be connected to the ligand for IRAK4 protein by a linker to form PROTAC IRAK4 degrader-1.

K-Ras ligand-Linker Conjugate 5 is a chemical compound that combines a ligand for the K-Ras recruiting moiety with a PROTAC linker. This linker is responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. The K-Ras ligand-Linker Conjugate 5 plays a crucial role in the synthesis of PROTAC K-Ras Degrader-1, a highly potent K-Ras degrader. In SW1573 cells, this degrader exhibits an impressive degradation efficacy of ≥70% [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].

K-Ras ligand-Linker Conjugate 4 is a chemical compound that combines a ligand for K-Ras recruiting moiety with a PROTAC linker. This linker is responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. The compound has the potential to be used in the synthesis of PROTAC K-Ras Degrader-1, a powerful degrader of K-Ras that has been shown to exhibit a degradation efficacy of ≥70% in SW1573 cells[1].

PROTAC IDO1 Degrader-1, a pioneering compound, efficiently targets indoleamine 2,3-dioxygenase 1 (IDO1) for ubiquitination and degradation by recruiting IDO1 to the CRBN E3 ligase, thereby facilitating its entry into the ubiquitin-proteasome system (UPS) with a DC50 of 2.84 μM. This compound also moderately enhances the tumor-killing efficacy of HER2 CAR-T cells[1].

CDK9 Antagonist-1 (compounds 11c) is a potent and selective CDK9 degrader based on PROTAC, with an IC50 of 17 μM in MCF-7 cell lines. Natural product Wogonin binds ubiquitin E3 ligase cereblon (CRBN) via a linker to form PROTAC[1]. CDK9|17 μM (IC50, MCF-7 cells) [1]. Bian J , et al. Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity. Bioorg Chem. 2018 Dec;81:373-381.

TD-165, a PROTAC-based cereblon (CRBN) degrader, consists of a cereblon (CRBN) ligand-binding group, a linker, and a von Hippel-Landau (VHL) binding group[1].

Thalidomide-C2-amido-C2-COOH is a compound that includes a CRBN ligand for the E3 ubiquitin ligase, as well as a linker. It is utilized in the development of PROTAC CDK2/9 Degrader-1[1].

SJ988497 is a PROTAC JAK2 degrader that effectively inhibits proliferation in CRLF2-rearranged (CRLF2r) cells and facilitates the degradation of the CRBN neosubstrate GSPT1. Composed of a Ruxolitinib derivative, a linker, and the CRBN ligand Pomalidomide, SJ988497 is utilized in researching acute lymphoblastic leukemia (ALL) [1].

PROTAC HSP90 degrader BP3 potently and selectively degrades HSP90 through a CRBN-dependent mechanism. It effectively diminishes HSP90 protein levels in MCF-7 cells with a half-maximal degradation concentration (DC50) of 0.99 µM. Additionally, this compound impedes the proliferation of breast cancer cells [1].

K-Ras ligand-Linker Conjugate 2 is a chemical compound that includes a ligand for K-Ras and a PROTAC linker. This compound is capable of recruiting E3 ligases like VHL, CRBN, MDM2, and IAP. It is utilized in the synthesis of PROTAC K-Ras Degrader-1, which is a highly effective PROTAC K-Ras degrader with a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 3 (Compound 001371) is a chemical compound that consists of a ligand for K-Ras recruiting moiety and a PROTAC linker, responsible for recruiting E3 ligases (e.g., VHL, CRBN, MDM2, and IAP). This compound is essential in the synthesis of PROTAC K-Ras Degrader-1, a potent PROTAC K-Ras degrader that demonstrates a degradation efficacy of ≥70% in SW1573 cells[1].

PROTAC BRD2/BRD4 degrader-1 (compound 15) serves as a potent, selective degrader of BET proteins BRD4 and BRD2, achieving rapid, reversible, and unexpectedly selective elimination of BRD4 and BRD2 compared to BRD3. Its efficacy in suppressing solid tumors manifest with minimal cytotoxic effects. This compound comprises a BET inhibitor, a connecting linker, and thalidomide as the ligand for cereblon (CRBN)/cullin 4A[1].

PROTAC MLKL Degrader-1 (Compound 36) is a selective PROTAC degrader targeting MLKL, achieving a degradation maximum (D max) over 90%. The compound encompasses modified cereblon (CRBN) ligands and a lenalidomide-linker as part of its structure. It effectively inhibits cell death in a TSZ-induced model of necroptosis.