PROTAC Selection

Glycodeoxycholic Acid is an endogenous metabolite, a natural product found in Streptomyces niger, Trypanosoma brucei, and Cryptomonas, which induces hepatocyte necrosis and autophagy in patients with obstructive cholestasis.

Tri-GalNAc-COOH is a ligand for the asialoglycoprotein receptor (ASGPR) commonly employed in Lysosome Targeting Chimera (LYTAC) investigations.

cis VH 032, amine dihydrochloride ((S,S,S)-AHPC) is a negative control for the functionalized VHL ligand VH 032, amine .

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. β-NF-JQ1 uses β-NF as an AhR ligand to target bromodomain (BRD)-containing proteins and induce AhR and BRD protein interactions. β-NF-JQ1 shows potent anticancer activity associated with protein knockdown activity. .

VH032 commonly used as a precursor to a PROTAC that hijacks VHL as the E3 ubiquitin ligase component.VH032 is a VHL/HIF-1α interaction inhibitor with a KdPROTACs, which can recruit von Hippel-Lindau (VHL) proteins as a ligand of VHL.

Fmoc-PEA (Example 1-2) is a used as a cleavable linker for antibody-drug conjugates (ADC).

dMCL1-2 is a potent and selective myeloid leukemia 1 (MCL1) degrading agent based on PROTAC, which binds to MCL1 with a KD of 30 nM. dmcl-2 activates the apoptosis mechanism by degrading MCL1.This compound is unstable in powder form and other related salt forms are recommended.

FKBP12 PROTAC dTAG-7 (dTAG-7) is a heterobifunctional compound that selectively degrades the BET bromodomain transcriptional co-activator BRD4 by connecting BET bromodomains to the E3 ubiquitin ligase CRBN. Additionally, it serves 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).

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

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.

PROTAC BRD4 Degrader-1 is an efficacious degrader of BRD4(BRD4 BD1,IC50 of 41.8 nM).

PROTAC FLT-3 degrader 1 is a PROTAC FLT-3 degrader of internal tandem duplication (ITD)(IC50 0.6 nM),with anti-proliferative activity.

BETd-246 is an inhibitor of second-generation and PROTAC-based BET bromodomain (BRD), show antitumor activity.

MZP-54 is a selective degrader of BRD3/4 based on PROTAC technology(Kd of 4 nM for Brd4BD2)

PROTAC BET Degrader-1 is a potent degrader of BET based on PROTAC.

ZXH-3-26 is a selective degrader of the PROTAC BRD4 (DC50/5h: ~ 5 nM).

PROTAC EED degrader-2 is a PROTAC targeting EED (pKD of 9.27),is a inhibitor of polycomb repressive complex 2 (PRC2) with pIC50 of 8.11.

TL13-112 is a selective degrader of ALK-PROTAC and inhibits ALK activity (IC50: 0.14 nM).

ERD-308 induces >95% of ER degradation at concentrations as low as 5 nM in both cell lines (DC50 (concentration causing 50% of protein degradation) of 0.17 nM and 0.43 nM in MCF-7 and T47D ER+ cells, respectively).ERD-308 is a highly potent PROTAC degrade

SJFα is a 13-atom linker PROTAC. SJFα degrades p38α with a DC50 of 7.16 nM, but is far less effective at degrading p38δ (DC50=299 nM) and does not degrade the other p38 isoforms (β and γ) at concentrations up to 2.5 μM[1].

INY-03-041, a potent and highly selective PROTAC-based pan-AKT degrader, inhibits AKT1, AKT2, and AKT3 with IC50s of 2.0 nM, 6.8 nM, and 3.5 nM, respectively. This compound consists of the ATP-competitive AKT inhibitor GDC-0068 conjugated to Lenalidomide.

CP5V, a PROTAC, induces mitotic inhibition, and suppresses cancer cell proliferation. It specifically degrades Cdc20 by linking Cdc20 to the VHL/VBC complex for ubiquitination followed by proteasomal degradation.

(S,R,S)-AHPC-PEG6-C4-Cl is a small molecule HaloPROTAC that incorporates the (S,R,S)-AHPC based VHL ligand and 6-unit PEG linker. (S,R,S)-AHPC-PEG6-C4-Cl is capable of inducing the degradation of GFP-HaloTag7 in cell-based assays[1].

JH-XI-10-02 causes proteasomal degradation, does not affect CDK8 mRNA levels. JH-XI-10-02 shows no effect on CDK19. JH-XI-10-02 is a potent and selective degrader of CDK8, with an IC50 of 159 nM, based on PROTAC.

MS4077 is an degrader of anaplastic lymphoma kinase (ALK) PROTAC(Kd of 37 nM for binding affinity to ALK).

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.

(S,R,S)-AHPC-C6-PEG3-C4-Cl is a small molecule HaloPROTAC that incorporates the (S,R,S)-AHPC based VHL ligand and 3-unit PEG linker. (S,R,S)-AHPC-C6-PEG3-C4-Cl is capable of inducing the degradation of GFP-HaloTag7 in cell-based assays[1].

PROTAC RIPK degrader-2 is a nonpeptidic PROTAC ,and potently targets serine-threonine kinase RIPK2 and has highly selective for RIPK2 degradation.

KB02-SLF is a PROTAC-based nuclear FKBP12 degrader, known as a molecular glue. It facilitates the degradation of nuclear FKBP12 by covalently modifying DCAF16, an E3 ligase. Moreover, KB02-SLF enhances the longevity of protein degradation in biological systems. The compound SLF acts as a linker, binding to the ubiquitin E3 ligase ligand KB02, resulting in the formation of KB02-SLF[1].

TL13-12 is a selective degrader of ALK-PROTAC and inhibits ALK activity (IC50: 0.69 nM).

GNE-987 is a highly active chimeric BET degrader. GNE-987 binds equipotently to the BD1 and BD2 bromodomains of BRD4 with low nanomolar affinities (IC50: 4.7 and 4.4 nM, respectively). GNE-987 exhibits picomolar cell BRD4 degradation activity (DC50: 0.03

PROTAC BET degrader-2 is a highly potent degrader of Bromodomain and Extra-Terminal (BET) proteins (IC50 of 9.6 nM ).

FKBP12 PROTAC dTAG-13 (dTAG-13) is a degrader of FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. FKBP12 PROTAC dTAG-13 (dTAG-13) also is a selective degrader of BET bromodomain transcriptional co-activator BRD4 by bridging BET bromodomains to an E3 ubiquitin ligase CRBN. FKBP12 PROTAC dTAG-13 (dTAG-13) is a PROTAC-based heterobifunctional degrader.

PROTAC FAK degrader 1 is a selective and potent degrader of focal adhesion kinase (Fak) (IC50 of 6.5 nM).

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.

PROTAC Sirt2 Degrader-1 is a SirReal-based PROTAC, acts as a Sirt2 degrader, composed of a highly potent and isotype-selective Sirt2 inhibitor, a linker, and a bona fide cereblon ligand for E3 ubiquitin ligase. PROTAC Sirt2 Degrader-1 shows an IC50 of 0.25 μM for Sirt2, with no effect on Sirt1/Sirt3 (IC50s > 100 μM)[1].

VZ185 is an effective and selective dual BRD7/9 PROTAC degrader (DC50s: 4.5 and 1.8 nM, respectively).

PROTAC PARP1 degrader is a degrader of PARP1 based on the PROTAC technology. PROTAC PARP1 degrader at 10 μM at 24 h inhibits MDA-MB-231 cell line (IC50 of 6.12 μM).

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).

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

CP-10 is a PROTAC with highly selective and remarkable CDK6 degradation (DC50: 2.1 nM). It inhibits the proliferation of several hematopoietic cancer cells including multiple myeloma and can degrade mutated and overexpressed CDK6.

ARCC-4 is an enzalutamide-based von Hippel-Lindau (VHL)-recruiting AR PROTAC and outperforms enzalutamide and it is a low-nanomolar androgen receptor (AR) degrader based on PROTAC, with a DC50 of 5 nM. ARCC-4 effectively degrades clinically relevant AR mutants associated with antiandrogen therapy[1].

PROTAC K-Ras Degrader-1 is potent degrader of K-Ras based PROTAC.

PROTAC BRD9 Degrader-1 is a lead PROTAC BRD9 chemical degrader with IC50 of 13.5 nM.

dFKBP-1 is a potent and PROTAC-based FKBP12 degrader. dFKBP-1 incorporates the ligand SLF of FKBP12, the Thalidomide based cereblon ligand and a linker[1].

SIAIS178 is a potent and selective degrader of BCR-ABL based on PROTAC technology (IC50 of 24 nM).

(S,R,S)-AHPC-PEG2-C4-Cl is a small molecule HaloPROTAC that incorporates the (S,R,S)-AHPC based VHL ligand and 2-unit PEG linker. (S,R,S)-AHPC-PEG2-C4-Cl is capable of inducing the degradation of GFP-HaloTag7 in cell-based assays[1].

MZP-55 is a selective BRD3/4 degrader based on PROTAC technology(Brd4BD2 with Kd of 8 nM)