Ligands for Target Protein for PROTAC

(+)-JQ-1 (JQ1) is a specific, reversible BET bromine domain inhibitor that targets BRD4 (1 2) with IC50 values of 77 33 nM. (+)-JQ-1 induces cell autophagy and inhibits cell proliferation.

PROTAC BRD4 ligand-1, a component of Protac GNE-987, is a ligand for BRD4 and acts as an inhibitor of BET.

Ibrutinib (PCI-32765) is an irreversible inhibitor of BTK (IC50: 0.5 nM) that selectively blocks B cell activation.

AR antagonist 1 is a potent antagonist of the androgen receptor. It binds to E3 ligase ligands with weak binding affinities to VHL protein in the synthesis of PROTAC ARD-266.

CPI-0610 carboxylic acid is an effective and selective small molecule inhibitor of bromine domain and outer end (BET) protein as a ligand of PROTAC target protein. CPI-0610 carboxylic acid may have anticancer and anticancer activities.

Quizartinib (AC220) is an inhibitor of FLT3 (Kd: 1.6 nM) and demonstrates high selectivity for FLT3 when tested against a panel of 227 additional kinases.

BI-4464, a highly selective ATP-competitive inhibitor of PTK2 FAK, exhibits an IC50 of 17 nM and serves as a PTK2 ligand for PROTAC (Proteolysis Targeting Chimera).

DUPA (N,N''-Carbonylbis[L-glutamic acid]) is used as the targeting moiety to actively deliver DTX for treatment of Prostate-Specific Membrane Antigen (PSMA) expressing prostate cancer.

Dasatinib carbaldehyde (PROTAC ABL binding moiety 4) is based on Dasatinib which is an ABL inhibitor, binds to the IAP ligand via a linker, and forms SNIPER [1].

Navitoclax-piperazine (ABT-263-piperazine) is a B-cell lymphoma extra large (BCL-XL) inhibitor.

TMX-4153 is a bivalent degrader that selectively targets and rapidly degrades endogenous PIP4K2C through recruitment of the von Hippel-Lindau (VHL) E3 ligase complex, demonstrating a K D of 42 nM. It is applicable in the synthesis of PROTAC [1].

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.

AZD9496 deacrylic acid phenol (AZD9496) represents a portion of the ligand that targets the protein for PROTAC ER Degrader-4 [1].

CFT1946 is a selective and orally active ligand targeting BRAF kinase, functioning as a degrader of mutant BRAF forms including BRAFV600E, G469A, G466V, and p61-BRAFV600E. It is utilized in tumor research [1].

PROTAC PTK6 ligand-1 serves as an intermediate in the synthesis of BTK kinase inhibitors [1] and is utilized in the preparation of ARD-61 [2].

Tazemetostat de(methyl morpholine)-COOH (compound 7), a PROTAC ligand for EZH2, enables the synthesis of PROTACs targeting this enzyme and exhibits potent inhibition of cell viability in diffuse large B-cell lymphoma (DLBCL) and other lymphoma subtypes [1].

SMD-3040 TFA is a selective SMARCA2 degrader, consisting of SMARCA2 4 ligands, a linker, and VHL ligands, used in PROTAC drug synthesis. It effectively inhibits tumor growth in xenograft models [1].

Abemaciclib metabolite M18 (LSN3106729) is a potent cyclin-dependent kinase (CDK) inhibitor with antitumor properties. It has been incorporated alongside a cereblon (CRBN) ligand to develop a proteolysis-targeting chimera (PROTAC) that selectively degrades CDK4/6 [1] [2].

PROTAC BRD4 Ligand-2 Hydrochloride serves as a ligand targeting the BRD4 protein, specifically designed for use with PROTAC CFT-2718.

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].

Phthalimide-PEG3-C2-OTs (Compound 5) is a PROTAC linker composed of PEGs, utilized in the synthesis of various PROTACs that connect two distinct ligands through a linker. One ligand targets an E3 ubiquitin ligase, while the other targets the specific protein of interest, enabling selective protein degradation through the ubiquitin-proteasome system [1].

m-PEG-azide (MW 2000) is a PEG-based linker used in PROTACs to join two essential ligands, facilitating the selective degradation of target proteins through the ubiquitin-proteasome system within cells.

Thalidomide-5-NH-PEG1-NH2 hydrochloride is a Thalidomide-based cereblon ligand designed for CRBN protein recruitment. It facilitates the formation of PROTAC molecules by linking to target protein ligands, such as THAL-SNS-032, via a connector.

Pomalidomide 4'-PEG5-amine, a cereblon ligand designed for PROTAC research and development, features an integrated E3 ligase ligand and a PEG5 linker ending in an amine for easy conjugation to target protein ligands. It is among a series of functionalized tool molecules specifically crafted for PROTAC R&D.

Diethylene Glycol Monobenzyl Ether is a PEG-based linker for PROTAC synthesis[1], facilitating the connection of target protein ligands and E3 ligase ligands to enable targeted protein degradation.

VH 101, acid, a functionalized von-Hippel-Lindau (VHL) protein ligand, facilitates PROTAC research and development. It comprises an E3 ligase ligand and an alkyl linker featuring a terminal amine for easy conjugation to target protein ligands [1].

7-Octynoic acid (compound 42) serves as a PROTAC linker for synthesizing various PROTACs, composed of two distinct ligands joined by this linker, where one ligand interacts with an E3 ubiquitin ligase and the other binds to the target protein, leveraging the intracellular ubiquitin-proteasome system to selectively degrade target proteins[1].

VH 032 amide-alkylC7-acid is a specialized compound designed for PROTAC research and development, serving as a functionalized von-Hippel-Lindau (VHL) protein ligand. It combines an E3 ligase ligand with an alkylC7 linker, ending in a terminal carboxylic acid for efficient conjugation to target protein ligands. This compound is among a series of functionalized tool molecules aimed at facilitating PROTAC R&D efforts.