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.

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.

Luxdegalutamide (ARV-766) is a novel, potent, and orally bioavailable proteolytic targeting chimera (PROTAC) protein degrader that degrades not only wild-type AR but also clinically relevant AR LBD mutants, including the most prevalent AR L702H, H875Y, and T878A mutations.

AU-15330 is a proteolytic targeting chimera (PROTAC) that simultaneously targets SMARCA4, SMARCA2, and PBRM1 for degradation and exhibits cytotoxicity in H3.3K27M cells but not in H3 wild-type cells. [2]

FKBP12 PROTAC dTAG-7 (dTAG-7) is a heterobifunctional compound that selectively degrades the BET bromodomain transcriptional co-activator BRD4 by linking BET bromodomains to the E3 ubiquitin ligase CRBN. It also functions as a degrader of FKBP12F36V when FKBP12F36V is expressed in-frame with a targeted protein.

QCA570 is an effective BET degrader based on PROTAC (IC50: 10 nM for BRD4 BD1 Protein).

(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.

CCT367766 is a potent, PROTAC-based, third-generation, iso-functional pirin-targeted protein degradation probe (PDP) that depletes pirin expression at low concentrations.CCT367766 has an IC50 value of 490 nM for the CRBN-DDB1 complex.CCT367766 has a good affinity for recombinant pirin and CRBN. CCT367766 has a good affinity for recombinant pirin and CRBN, with Kd values of 55 nM and 120 nM, respectively. cct367766 is a potent orally active protein that reduces the expression of pirin at low concentrations.

NH2-PEG2-C6-Cl hydrochloride is a PROTAC linker belonging to the PEG class and can be used to synthesize PROTAC molecules.

DSPE-PEG4-DBCO is a PEG-based linker for PROTACs that joins two essential ligands, essential for forming PROTAC molecules, enabling selective protein degradation by leveraging the ubiquitin-proteasome system within cells.

Pomalidomide-PEG3-OH enables the synthesis of molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology.

Pomalidomide-PEG2-OH enables the synthesis of molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology.

MS170 is a highly effective and specific PROTAC AKT degrader compound that exhibits potent activity. It efficiently reduces the levels of total AKT (T-AKT) within cells, with a DC 50 value of 32 nM. Furthermore, MS170 demonstrates strong binding affinity towards AKT isoforms, specifically AKT1, AKT2, and AKT3, with respective dissociation constants (Kd) of 1.3 nM, 77 nM, and 6.5 nM.This compound is unstable in powder form and other related salt forms are recommended.

BETd-260, a PROTAC linked by a Cereblon ligand and a BET ligand, has an inhibitory effect on BRD4 protein in leukemic cell lines.

β-NF-JQ1 is a PROTAC that recruits aryl hydrocarbon receptor E3 (AhR E3) ligase to target proteins. Using β-NF as an AhR ligand, it targets bromodomain (BRD)-containing proteins and induces AhR and BRD protein interactions. β-NF-JQ1 exhibits potent anticancer activity associated with protein knockdown activity.

FC 11 is a highly potent focal adhesion Ki nase (FAK) PROTAC®Degrader (DC50 values are 40 to 370 pM depending on cell line), which is composed of the FAK inhibitor PF 562217 joined by a linker to the cereblon-binding ligand Pomalidomide. The effects of FC 11 are reversible upon compound wash out. FC 11 also degrades autophosphorylated FAK (pFAKtyr397), displaying near complete degradation after 3 hours at 100 nM in TM3 cells.

MS67 is a potent and selective degrader of WD40 repeat domain protein 5 (WDR5) with a dissociation constant (Kd) of 63 nM, exhibiting no activity against protein methyltransferases, kinases, G-protein-coupled receptors (GPCRs), ion channels, and transporters, and notably demonstrating significant anticancer properties.

BSJ-4-116 is a highly potent and selective CDK12 degrader (PROTAC) with an IC50 of 6 nM. It downregulates DDR genes through a premature termination of transcription, primarily through increasing poly(adenylation).

dBET6 is a selective and cell-permeable degrader of BET based on PROTAC (IC50: 14 nM). It has antitumor activity.

dCBP-1 is a chemical degrader of p300 CBP. dCBP-1 hijacks the E3 ubiquitin ligase CRBN for selective degradation of p300 CBP. Degradation of p300 CBP by dCBP-1 leads to effective multiple myeloma cell killing.

JQAD1 is a potent and selective histone acetyltransferase EP300 degrader (PROTAC®; DC50≤ 31.6 nM); comprises an EP300 inhibitor, A485, joined by a linker to a cereblon E3 ligase ligand. JQAD1 brings about degradation of EP300 in neuroblastoma cell lines in a proteasome-dependent manner. JQAD1 suppresses both H3K27ac and EP300 expression levels and induces apoptosis. JQAD1 suppresses tumors growth in NSG mice xenografted with Kelly cells. CRC and MYCN genes are downregulated in tumors treated with JQAD1. JQAD1 exhibits no significant effect on coactivator CBP at concentrations inducing EP300 degradation.

A1874 is a nutlin-based and BRD4-degrading PROTAC which induces BRD4 degradation in cells. Effective in inhibiting many cancer cell lines proliferation.

BSJ-03-123 is a potent, CDK6-selective small-molecule degrader.

GMB-475 is a BCR-ABL1 tyrosine kinase degrader based on PROTAC, overcoming BCR-ABL1-dependent drug resistance. GMB-475 targets BCR-ABL1 protein and recruits the E3 ligase Von Hippel Lindau (VHL).resulting in ubiquitination and subsequent degradation of th

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

Gefitinib-based PROTAC 3, which connects an EGFR binding element to a VHL ligand via a linker, induces EGFR degradation with DC50s of 11.7 nM and 22.3 nM in HCC827 (exon 19 del) and H3255 (L858R mutation) cells, respectively[1].

MS4078 is an inhibitor and aplastic lymphoma kinase (ALK) PROTAC (degrader) based on Cereblon ligand, with a Kd of 19 nM for binding affinity to ALK.

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

Homo-PROTAC pVHL30 degrader 1 is a potent PROTAC-based degrader of pVHL30.

ACBI1 is a potent PROTAC degrader of BAF ATPase subunits SMARCA2 and SMARCA4, also degrades the polybromo-associated BAF (PBAF) complex member PBRM1, with DC50s of 6 nM, 11 nM and 32 nM for SMARCA2, SMARCA4 and PBRM1 in MV-4-11 cells, respectively. ACBI1 is composed of a bromodomain ligand, a linker, and the E3 ubiquitin ligase VHL. ACBI1 can induce anti-proliferative effects and apoptosis.

MT-802 is an effective BTK degrader based on PROTAC technology (DC50: 1 nM). MT-802 has the potential to treat C481S mutant chronic lymphocytic leukemia (CLL).

THAL-SNS-032 is a PROTAC designed to selectively degrade CDK9.

ARV-393 is a BCL6 PROTAC degrader with DC50 and GI50 values of <1 nM in both DLBCL and BL cell lines. ARV-393 inhibits tumor volume in multiple tumor xenograft models.

BRD4 degrader AT1 is a highly selective Brd4 degrader based on PROTAC technology, with a Kd of 44 nM for Brd4BD2 in cells.

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].

m-PEG12-DBCO is a PEG-based linker for PROTACs that connects two essential ligands, facilitating the formation of PROTAC molecules. This linker promotes selective protein degradation by utilizing the ubiquitin-proteasome system within cells.

MZ 1 is a BRD4 protein degrader based on PROTAC technology.

Diazo Biotin-PEG3-alkyne is a polyethylene glycol (PEG)-based linker designed specifically for the synthesis of proteolysis-targeting chimeras (PROTACs) [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].

DP-C-4 is a Cereblon-based dual PROTAC for simultaneous degradation of EGFR and PARP[1]. DP-C-4 (1-50 μM; 24 hours) has degradation effects on EGFR and PARP simultaneously in a dose-dependent manner in SW1990 cells[1]. [1]. Mengzhu Zheng, et al. Rational Design and Synthesis of Novel Dual PROTACs for Simultaneous Degradation of EGFR and PARP. J Med Chem. 2021 May 26.

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.

ARV-825, a heterobifunctional PROTAC (Proteolysis Targeting Chimera) that recruits BRD4 to the E3 ubiquitin ligase cereblon leading to fast, efficient, and prolonged degradation of BRD4 in all BL cell lines tested.

Benzyl-PEG12-alcohol is a PEG-based linker for PROTACs, connecting two essential ligands to form PROTAC molecules. This linker facilitates selective protein degradation by utilizing the ubiquitin-proteasome system within cells.

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

dBET57 is heterobifunctional degrader of BRD4 based on the PROTAC technology, exhibits significant degradation of BRD4BD1 with a DC50/5h of 500 nM ,and inactive on BRD4BD2

UNC6852 contains an EED ligand (IC50 = 247 nM) and a von Hippel-Lindau ligand and is a selective polycomb repressive complex 2 (PRC2) degrader based on PROTAC.

PROTAC CDK9 Degrader-1 is a selective degrader of cyclin-dependent kinase 9 (CDK9).

ARD-2128 is a highly potent, orally bioavailable PROTAC (proteolysis-targeting chimera) that degrades the androgen receptor (AR), effectively reducing AR protein levels, suppressing AR-regulated gene expression in tumor tissues, and inhibiting tumor growth without evident toxicity. This compound holds promise for prostate cancer research.