PROTAC

Pomalidomide is a derivative of thalidomide and acts as an immunomodulator.

PROTAC Mcl1 degrader-1 (compound C3), a proteolysis targeting chimera (PROTAC), is a potently and selectively Mcl-1 inhibitor with an IC50 of 0.78 μM.

SNIPER(ABL)-062, in which an ABL inhibitor is linked to a ligand of cIAP1 via a linker containing a variable polyethylene glycol (PEG) unit, shows a potent activity to degrade the BCR-ABL protein.

BC-1215 is an inhibitor of F-box protein 3 (FBXO3, a ubiquitin E3 ligase component, IC50=0.9 μg/mL for IL-1β release). BC-1215 decreases Fbxo3-Fbxl2 interaction and prevents SCFFbxo3 catalyzed Fbxl2 ubiquitination.

BI-4464 is a highly selective ATP competitive inhibitor of PTK2/FAK, with an IC50 of 17 nM. A PTK2 ligand for PROTAC.

SNIPER(BRD4)-1 is a specific and nongenetic inhibitor of apoptosis protein (IAP)-dependent protein eraser (SNIPER) which acts as a protein degradation inducer of bromodomain-containing protein 4 (BRD4).

SirReal1-O-propargyl is a selective and highly potent Sirtuin 2 (Sirt2) inhibitor, with an IC50 of 2.4 μM.

I-BET762 carboxylic acid (Molibresib carboxylic acid) is an I-BET762-based warhead ligand for conjugation reactions of PROTAC targeting on BET. I-BET762 carboxylic acid (Molibresib carboxylic acid) is a BRD4 inhibitor with a pIC50 of 5.1.

PROTAC BET-binding moiety 2 is an inhibitor of BET bromodomain.

Apcin-A, an Apcin derivative, is an anaphase-promoting complex (APC) inhibitor.

DB0614 is a PROTAC molecule utilizing a cereblon ligand, designed as a selective and potent degrader of NEK9 and other kinases. It induces the degradation of multiple kinases, including ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1–3, MAP4K5, MAPK14, MAPK7–9, MAPKAPK2/3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1/3, SIK2/3, STK35, TNK2, and ULK1. DB0614 is suitable for research involving diseases or disorders driven by aberrant kinase activity.

Zelebrudomide (NX-2127) is a novel, potent BTK degrader that induces proteasomal degradation through targeted ubiquitination, rather than direct inhibition. In addition to degrading BTK, Zelebrudomide (NX-2127) enhances immune responses by stimulating T cell activation and increasing IL-2 production in primary human T cells, supporting its potential in cancer and immunotherapy research.

dTAGV-1-NEG is a diastereomer that acts as a heterobifunctional negative control for dTAGV-1, specifically targeted at FKBP12(F36V). This compound is utilized in research to study the selectivity and efficacy of FKBP12(F36V) degraders, helping to elucidate cellular mechanisms and pathways influenced by FKBP12 modulation. Its role as a control reagent makes it essential for validating experimental results in protein degradation studies.

VEGFR-2-IN-39 is a potent inhibitor of the vascular endothelial growth factor receptor 2 (VEGFR-2), with an IC50 of 208.6 nM. This compound effectively inhibits the proliferation of EA.hy926 cells, a human umbilical vein endothelial cell line, in a concentration-dependent manner, exhibiting an IC50 of 38.65 µM. VEGFR-2-IN-39 has low toxicity, making it suitable for further research applications in angiogenesis and vascular biology.

JPS016 is a class I histone deacetylase (HDAC) PROTAC inhibitor that targets HDAC1, HDAC2, and HDAC3 for ubiquitination and proteasomal degradation via VHL E3 ligase recruitment. This compound demonstrates significant anticancer activity by reducing the viability of colon cancer cells and inducing apoptosis. Additionally, JPS016 activates the PINK1/Parkin-mediated mitochondrial autophagy pathway, enhancing cardiomyocyte viability, alleviating mitochondrial damage, and decreasing mitochondrial ROS production. It is valuable for research into colon cancer and sepsis-related cardiac dysfunction.

TLR4-IN-C34-C2-COOH is a TLR4 inhibitor that serves as a PROTAC linker. It demonstrates significant potential in the modulation of inflammatory responses, particularly in studies involving acute myocardial injury. By targeting TLR4 in enterocytes and macrophages, TLR4-IN-C34-C2-COOH effectively reduces systemic inflammation in murine models of endotoxemia and necrotizing enterocolitis, making it a valuable tool for research in inflammation-related pathways.

SMARCA2-IN-8 is a selective inhibitor of the SWI/SNF chromatin remodeling complexes SMARCA2 and SMARCA4, exhibiting potent activity with IC50 values of 5 nM and 6 nM, respectively. This compound effectively inhibits the proliferation of SMARCA2-mutated cancer cells, specifically SKMEL5, with an AAC50 of 5 nM and downregulates SMARCA2-dependent KRT80 gene expression at an AAC50 of 10 nM. SMARCA2-IN-8 demonstrates substantial antitumor efficacy and favorable pharmacokinetic properties in preclinical mouse models, making it a valuable tool for investigating chromatin remodeling in cancer research.

SMARCA2-IN-2 is a specific inhibitor of SMARCA2, demonstrating an IC50 range of 101-500 µM. This compound is relevant for investigations into cancer biology, as it provides insights into the role of SMARCA2 in tumorigenesis. Its ability to selectively modulate SMARCA2 activity makes it a valuable tool for understanding epigenetic regulation in cancer research.

SR-5037 is an orally active inhibitor of CDK12 and CDK13, with an IC50 of 31 nM, and functions as a molecular glue degrader for CycK, demonstrating a DC50 of 30 nM and Dmax exceeding 98%. By inhibiting the enzymatic activity of the CDK12/CycK and CDK13/CycK complexes, SR-5037 facilitates the recruitment of DDB1, leading to proteasome-mediated degradation of CycK. This compound has shown efficacy in degrading active CycK in mouse models of triple-negative breast cancer and is a valuable tool for investigating treatment options in such malignancies.

PVTX-405 is a selective, orally bioavailable inhibitor targeting IKZF2, designed as a molecular glue degrader. With a DC50 of 0.7 nM and a Dmax of 91%, it enhances degradation efficiency while minimizing off-target effects, exhibiting an IC50 of 48 µM for hERG inhibition. PVTX-405 demonstrates significant antitumor activity by inhibiting the growth of MC38 tumors and shows improved efficacy when combined with immune checkpoint therapies, such as anti-PD1 or anti-LAG3, in mouse models.

MEL24 is an inhibitor of the Mdm2 E3 ligase, which plays a critical role in regulating p53 protein levels. This compound significantly reduces cell survival and enhances sensitivity to DNA-damaging agents in a p53-dependent manner. MEL24 is primarily utilized in antitumor research, contributing to studies aimed at understanding and overcoming resistance in cancer therapies.

SJ1008066 is an inhibitor of the MAGE-A11 protein, demonstrating an IC50 of 0.13 μM. It specifically binds to the MAGE homology domain (MHD), effectively disrupting the interaction between MAGE-A11 and PCF11. This mechanism presents valuable opportunities for research into cancer biology and therapeutic strategies targeting MAGE-A11 associated pathways.

MEL23 is an MDM2 E3 ligase inhibitor that specifically targets the E3 ligase activity of the MDM2-MDMX complex. This compound effectively inhibits the ubiquitination of MDM2 and p53, leading to decreased viability in cells expressing wild-type p53. Additionally, MEL23 stabilizes MDM2 through a mechanism that does not involve p53 transcription, making it a valuable tool for research into cancer biology and therapeutic strategies targeting the p53 pathway.

PPACK dihydrochloride is a potent and selective irreversible inhibitor of thrombin. It serves as an alternative anticoagulant to lithium heparin for blood gas and electrolyte analyses in whole blood. Additionally, PPACK dihydrochloride inhibits plasminogen activator (rt-PA), preventing its binding to plasma protease inhibitors. This compound also reduces plasmin-induced endothelial permeability and morphological changes in bovine aortic endothelial cell monolayers, making it suitable for investigations in thrombosis-related research.

AD4 is a proteolytic targeting chimera (PROTAC) designed to inhibit PCLAF. This compound effectively degrades PCLAF in RS4;11 cells with an IC50 of 0.6 nM, leading to the activation of the p21/Rb pathway and demonstrating anti-tumor effects. In vivo studies have shown that AD4 prolongs survival in RS4;11-transplanted NOD/SCID mice, highlighting its potential for cancer research applications.