selectively

Ac4ManNAz is an azido-containing metabolic glycoprotein labeling reagent. It can be used to selectively modify proteins, and it can be used in cell labeling, tracking and proteomic analysis;

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

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.

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].

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.

Degrader targeting mutant FKBP12F36V fusion proteins. Comprises a ligand selective for F36V single-point mutated FKBP12, a linker and a von Hippel-Lindau (VHL)-binding ligand. Induces potent and selective degradation of FKBP12F36V fusion proteins in vitro and in vivo. Selectively degrades FKBP12F36V-EWS/FLI fusion proteins and inhibits cell proliferation in FKBP12F36V-EWS/FLI-expressing Ewing sarcoma cells. Hydrochloride salt (Cat.No. 7374) available; suitable for in vivo use. Negative control dTAGV-1-NEG (Cat. No. 6915) also available. FKBP12F36V can be expressed as a fusion with a target protein of interest using genome engineering techniques, via transgene expression or CRISPR-mediated locus-specific knock-in. Custom knock-in cell lines for the dTAG and aTAG platforms are available from our sister brand R&D Systems. Email TPD@bio-techne.com to enquire. Plasmid vectors for the lentiviral expression and CRISPR-mediated knock-in of FKBP12F36V are available from Addgene.

Phthalimide-PEG3-C2-OTs (Compound 5) is a PROTAC linker composed of PEGs. It is utilized in the synthesis of various PROTACs, which involve the connection of two distinct ligands through a linker. One ligand is specific for an E3 ubiquitin ligase, while the other ligand is designed for targeting the specific protein of interest. Through leveraging the intracellular ubiquitin-proteasome system, PROTACs are capable of selectively degrading target proteins [1].

SNIPER(ER)-87 is a chemical compound composed of a derivative of the inhibitor of apoptosis protein (IAP) ligand LCL161 conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen using a PEG linker. It effectively degrades the ERα protein with an IC50 value of 0.097 μM. Within cells, SNIPER(ER)-87 selectively recruits XIAP to ERα, and XIAP functions as the primary E3 ubiquitin ligase responsible for the degradation of ERα induced by SNIPER(ER)-87[1][2].

ACBI2, an orally active and highly potent VHL PROTAC (EC 50: 7 nM), selectively degrades SMARCA2, demonstrating a DC 50 value of 1 nM in RKO cells. This compound holds potential for lung cancer research [1].

(S,R,S)-AHPC-Me hydrochloride (VHL ligand 2 hydrochloride) is a chemical compound utilized in the synthesis of ARV-771, an exceptionally potent BET protein degrader. This compound selectively degrades BET protein in cells resistant to castration, exhibiting a remarkable DC50 <1 nM. Recognized as VHL ligand 2 hydrochloride, (S,R,S)-AHPC-Me hydrochloride serves as the VHL ligand derived from (S,R,S)-AHPC for the recruitment of von Hippel-Lindau (VHL) protein.

PROTAC EGFR degrader 8 (T-184) is a PROTAC that selectively degrades the epidermal growth factor receptor (EGFR) with a DC50 of 15.56 nM in HCC827 cells. It effectively inhibits the growth of various cell lines, including H1975, PC-9, and HCC827, with IC50 values of 7.72 nM, 121.9 nM, and 14.21 nM, respectively. This compound is primarily used for cancer research, particularly in the context of non-small cell lung cancer (NSCLC) [1].

SK-575 is a degradation agent targeting protein-hydrolyzed PARP1 chimera with anticancer and antitumor activity.SK-575 effectively inhibits the growth of cancer cells harboring BRCA1/2 mutations and selectively induces PARP1 degradation in cancer cells.

SNIPERTACC3-1 hydrochloride, an IAP ligand-based compound, selectively degrades the TACC3 protein through the ubiquitin-proteasome pathway, thereby inducing cancer cell apoptosis [1].

Folate-MS432 is a PROTAC that degrades MEKs selectively in cancer cells via folate receptor-dependent pathways.

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].

SJ1008030 (compound 8), a JAK2 PROTAC, selectively degrades JAK2. It demonstrates potent activity against MHH–CALL-4 cells, with an EC50 of 5.4 nM and an IC50 of 32.09 nM. This compound holds potential for leukemia research [1].

AZ'6421, functioning as a Proteolysis Targeting Chimera (PROTAC), selectively degrades estrogen receptor alpha, demonstrating potent anti-tumor activity by inhibiting uncontrolled cellular proliferation characteristic of malignant diseases. This compound holds promise for cancer research, including breast cancer applications [1].

Lenalidomide hemihydrate is a derivative of Thalidomide, an orally active immunomodulator that acts as a molecular gel. It is a ligand for the ubiquitin E3 ligase cereblon, which selectively ubiquitinates and degrades two lymphoid transcription factors, IKZF1 and IKZF3, via the CRBN-CRL4 ubiquitin ligase.

DCAF1 Binder 1 selectively targets the CRL4 DCAF1 E3 ligase complex as a ligand, playing a role in targeted protein degradation (TPD) [1].

ZXH-4-130 TFA is a hetero-PROTAC (CRBN-VHL compound) that efficaciously and selectively mediates the degradation of CRBN. At a concentration of 10 nM in MM1.S cells, ZXH-4-130 TFA achieves approximately 80% degradation of CRBN [1].

PROTAC AR-NTD antagonist 1 (compound 18) is a small molecule belonging to the protein-targeting chimeras (PROTACs) that selectively targets the N-terminal domain (AR-NTD) of the Androgen Receptor variant AR-V7. By antagonizing AR-NTD, this compound effectively degrades AR-V7 protein and triggers apoptosis in prostate cancer (PC) cells, with degradation efficiencies in VCaP cells recorded at 62.2% (1 μM) and 71.1% (5 μM), as noted in reference [1].

Boc-C1-PEG3-C4-OBn (PROTAC Linker 15) is a PEG-based PROTAC linker employed in the synthesis of various PROTACs, including PROTAC SGK3 degrader-1. PROTACs are composed of two distinct ligands connected by a linker; one ligand binds to an E3 ubiquitin ligase, while the other specifically interacts with the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs can selectively degrade target proteins[1].

DBCO-PEG4-triethoxysilane is a polyethylene glycol (PEG)-based linker compound that serves as an efficient building block for the synthesis of PROTACs. These PROTACs are small molecules designed to selectively target and degrade specific proteins of interest[1].

A-1210477-piperazinyl is a compound that specifically targets and binds to the protein myeloid cell leukemia 1 (MCL1). This compound is utilized in PROTAC technology, which harnesses the ability to selectively degrade target proteins.

PROTAC Bcl2 degrader-1 is a PROTAC, which potently and selectively induces the degradation of Mcl-1 (IC50: 11.81 μM) and Bcl-2 (IC50: 4.94 μM; DC50: 3.0 μM).

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 BRD3/BRD4-L degrader-2, a PROTAC molecule, selectively degrades cellular BRD3 and BRD4-L with K i values of 16.91 and 2.8 nM, respectively, and exhibits robust antitumor activity in mouse xenograft models, serving as a research tool for cancer [1].

SA-VA, an intracellular self-assembled PROTAC featuring azide and alkyne groups, selectively degrades VEGFR-2 and EphB4 proteins within U87 cells. This compound undergoes in situ conversion to active PROTAC via a copper-catalyzed click reaction utilizing endogenous copper present in tumor tissues. Additionally, SA-VA induces apoptosis and arrests cell cycle progression in the S phase [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].

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

ZXH-1-161 is a potent regulator of cereblon (CRBN) that acts on wild-type MM1.S cells (IC50: 39 μM). ZXH-1-161 selectively degrades GSPT1. ZXH-1-161 can be used to study multiple myeloma.

MS21 is a unique AKT degrader that selectively hampers the proliferation of cancers with mutations in the PI3K/PTEN pathway, alongside wild-type KRAS and BRAF.

SA-PA, a self-assembled intracellular PROTAC leveraging azide-alkyne click chemistry, selectively degrades VEGFR-2, PDGFR-β, and EphB4 proteins within U87 cells. In the presence of endogenous copper in tumor tissues, SA-PA undergoes in situ conversion to active PROTAC through a click reaction [1].

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

dBRD4-BD1 is a selective BRD4 bromodomain inhibitor. dBRD4-BD1 can selectively degrade BRD4 (DC50 = 280 nM). Notably, dBRD4-BD1 upregulates BRD2/3, a result not observed with degraders using pan-BET ligands. Designing BRD4 selectivity up front enables analysis of BRD4 biology without wider BET-inhibition and simplifies designing BRD4-selective heterobifunctional molecules, such as degraders with new E3 recruiting ligands or for additional probes beyond degraders.

Bis-PEG1-C-PEG1-CH2COOH (PROTAC Linker 26) is a PEG-based linker suitable for the synthesis of PROTACs, compound complexes that selectively degrade target proteins[1].

Phthalimide-PEG4-PDM-OTBS is a PROTAC linker comprised of polyethylene glycols (PEGs). This compound is utilized in the synthesis of a range of PROTACs, which consists of two distinct ligands connected by a linker. One ligand binds to an E3 ubiquitin ligase, while the other ligand binds to the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs selectively degrade target proteins[1].

m-PEG3-Sulfone-PEG4-propargyl is a polyethylene glycol (PEG)-based prodrug-induced degradation (PROTAC) linker. It is utilized in the efficient synthesis of PROTACs, a class of heterobifunctional molecules designed to selectively target and degrade specific protein targets[1].

SJF 1521 is an EGFR degrader belonging to the PROTAC class that selectively degrades EGFR while preserving HER2.

Dovitinib RIBOTAC TFA effectively and selectively cleaves pre-miR-21, functioning as a targeted RNA degrader.

Phthalimide-PEG4-MPDM-OH, a PROTAC linker with a PEGs composition, has applications in the synthesis of various PROTACs. These PROTACs consist of a linker connecting two distinct ligands: one binds to an E3 ubiquitin ligase, while the other binds to the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs selectively induce the degradation of target proteins [1].

Pomalidomide-amido-C4-amido-PEG2-C2-NH-Boc is a novel synthesized conjugate compound functioning as an E3 ligase ligand-linker in PROTAC technology. This compound incorporates a Pomalidomide-derived cereblon ligand, which binds selectively to the E3 ligase cereblon, and a 2-unit PEG linker, which provides stability and flexibility to the conjugate.

Bis-PEG5-acid (PROTAC Linker 36) is a polyethylene glycol (PEG) linker employed for the synthesis of CP5V, a PROTAC that selectively degrades Cdc20[1].

N-(Azido-PEG3)-N-bis(PEG3-acid) is a polyethylene glycol (PEG)-based linker that incorporates an azido group and two PEG3-acid moieties. This compound is widely applicable in the synthesis of proteolysis targeting chimeras (PROTACs), which are molecules with the ability to selectively degrade target proteins[1].