PROTACs

Vepdegestrant (ARV-471) is an estrogen receptor (ER) α PROTAC molecule that degrades ER in ER-positive breast cancer cell lines with a DC50 of approximately 1 nM. It can reduce the expression of classically regulated ER target genes and inhibit the growth of ER-dependent cell lines (including those expressing ESR1 variants, such as Y537S and D538G) by degrading ER.

PROTAC BRAF-V600E degrader-1 (Compound 23) selectively induces degradation of BRAF-V600E but not wildtype BRAF.

ARV-771 is an effective BET degrader based on PROTAC technology. The Kd for BRD2(1), BRD2(2), BRD3(1), BRD3(2), BRD4(1) and BRD4(2) are 34 and 4.7 respectively. , 8.3, 7.6, 9.6 and 7.6 nM.

C004019 is a small molecule PROTAC capable of targeting tau for selective protein degradation from the cell, while recruiting tau and E3 ligase (Vhl) for selective enhancement of tau ubiquitination and proteollyzation. C004019 is a candidate for AD and related tau protein diseases.

(Iso)-MS4322 ((Iso)-YS43-22) is a selective and potent protein arginine methyltransferase 5 (PRMT5) degrader with potential anticancer activity that effectively reduces PRMT5 protein levels in MCF-7 cells and inhibits the growth of a wide range of cancer cells.

GDC-2992 is a selective and oral AR (androgen receptor) degrader that inhibits the proliferation of tumor cells overexpressing AR, degrades AR (DC50 = 2.7 nM) and inhibits proliferation (IC50 = 9.7 nM) in VCaP cells, and can be used for oncology studies in denuded resistant prostate cancer (CRPC).

PROTAC BRD4 Degrader-29 (compound 7a) is a potent BRD4 PROTAC degrader with a DC50 of 89.4 nM, playing a significant role in cancer research.

PROTAC EGFR degrader 2 is a potent compound with an IC50 of 4.0 nM, demonstrating strong antiproliferative activity, and a DC50 of 36.51 nM, indicating robust EGFR degradation activity. It is suitable for synthesizing nitroreductase (NTR)-responsive PROTACs [1].

Azido-PEG2-VHL is a multikinase degrader used in the synthesis of PROTACs (PROteolysis TArgeting Chimeras) [1].

AD4, an artemisinin derivative functioning as a proteolytic targeting chimera (PROTAC) for PCLAF, effectively degrades PCLAF in RS4;11 cells with an IC50 of 0.6 nM. This degradation activates the p21 Rb axis, resulting in antitumor activity. Furthermore, AD4 has been demonstrated to prolong survival in NOD SCID mice transplanted with RS4;11 cells, showcasing its in vivo efficacy [1].

CCT367766 formic is a potent third-generation heterobifunctional Cereblon-based protein degradation probe (PDP, or PROTAC) that selectively targets pirin for degradation, effectively diminishing its protein expression at low concentrations. This compound demonstrates moderate affinity towards the CRBN-DDB1 complex, as denoted by an IC50 value of 490 nM, while exhibiting strong binding to recombinant pirin and CRBN, with respective Kd values of 55 nM and 120 nM. As such, CCT367766 formic serves as a valuable chemical probe for investigating the functions of the largely unexplored pirin protein [1].

PROTAC TTK Degrader-2 is a potent threonine tyrosine kinase (TTK) PROTAC degrader, achieving DC50 values of 3.1 nM in COLO-205 cells and 12.4 nM in HCT-116 cells. It demonstrates effective target degradation and anticancer activity in a COLO-205 human colorectal cancer cell xenograft mouse model [1].

PROTAC EGFR degrader 7 (compound 13b) is a potent, selective, CRBN-recruiting EGFRL858R T790M degrader with a DC50 of 13.2 nM. It effectively inhibits NCI-H1975 cell proliferation with an IC50 of 46.82 nM, induces apoptosis, and causes G2 M phase arrest. This compound shows antitumor activity and is applicable in non-small cell lung cancer (NSCLC) research.

PROTAC CYP1B1 Degrader-1 (Compound 6C), an α-naphthoflavone chimera derivative, effectively targets and degrades cytochrome P450 (CYP) 1B1 to overcome agent resistance, displaying half-maximal inhibitory concentrations (IC50s) of 95.1 nM for CYP1B1 and 9838.6 nM for CYP1A2. This compound is suitable for investigating prostate cancer characterized by overexpression of CYP1B1 [1].

PPM-3, a selective PROTAC ERK5 degrader, exhibits a potent inhibitory concentration (IC 50) of 62.4 nM. While not directly inhibiting tumor cell growth, PPM-3 affects tumor progression through influencing macrophage differentiation [1].

PZ703b TFA, a Bcl-xl PROTAC degradation agent, promotes apoptosis and halts bladder cancer cell proliferation, making it a pertinent investigative compound for related oncological studies [1] [2].

SJ1008030 (compound 8) TFA is a selective JAK2-degrading PROTAC that inhibits the growth of MHH-CALL-4 leukemia cells with an IC50 of 5.4 nM, demonstrating its potential for leukemia research [1].

PROTAC IRAK4 Ligand-3 serves as a ligand for PROTAC IRAK4 Degrader-7 and is utilized in cancer research [1].

PROTAC BRD9 Degrader-3 is a bifunctional degrader targeting BRD9, used in cancer research.

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].

SJF620 hydrochloride is a PROTAC that utilizes a lenalidomide analog to recruit CRBN and ligands to target Btk, exhibiting a DC50 of 7.9 nM [1].

PROTAC STING Degrader-1 (Compound SP23) is a STING-targeted PROTAC degrader with a DC50 of 3.2 μM, demonstrating anti-inflammatory activity [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].

PhoBET1 is a photocaged PROTAC that effectively induces BRD4 degradation, thus suppressing tumor growth [1].