PROTAC

ARV-766 is an orally effective protein degradation agent of protein hydrolysis targeted chimeras (PROTACs). ARV-766 degrades wild-type androgen receptor AR, as well as related AR LBD mutants, including the most common pathogenic AR L702H, H875Y and T878A mutations.

DB1113 (Example 24) is a bifunctional compound that targets protein kinase degradation. DB1113 can degrade ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1 , MAP4K2，MAP4K3，MAP4K5，MAPK14，MAPK7，MAP K8，MAP K9，MAP KAP K2，MAP KAP K3，NL K ，PDI K1L ，PT K2B ，RIP K1 ，RPS6KA1 ，RPS6KA3 ，SIk2、SIk3、ST k35、TN k2 and UL k1. DB1113 can be used to study diseases or disorders mediated by abnormal kinase activity.

Dovitinib RIBOTAC is a targeted RNA degrading agent that can efficiently and selectively cleave pre-miR-21.

Dovitinib RIBOTAC TFA is a targeted RNA degrading agent that can efficiently and selectively cleave precursor miR-21.

dTAG-47 is a bifunctional dTAG molecule that targets the mutant form of FKBP12 (FKBP12F36V). FKBP12F36V can be used as a degradation tag (dTAG) and fused with target proteins. dTAG-47 can be used for research on basal-like breast cancer (BBC).

JQAD1 is a CRBN-dependent PROTAC that selectively targets EP300 for degradation. JQAD1 inhibits the expression of EP300 and H3K27ac modification. JQAD1 induces apoptosis in cells. JQAD1 can be used for cancer research.

MS159 is an effective nuclear receptor binding SET domain protein 2 (NSD2) PROTAC degrader. MS159 can inhibit the growth of tumor cells. MS159 is an effective chemical tool for exploring the role of NSD2 in health and disease.

MS21 is a novel AKT degrader that selectively inhibits the growth of mutant cancers through the PI3K/PTEN pathway.

MS9427 is an effective PROTAC EGFR degrader, with Kd values of 7.1 nM and 4.3 nM for wild-type EGFR and mutant EGFR L858R, respectively. MS9427 selectively degrades mutant variants through the ubiquitin/proteasome system (UPS) and autophagy/lysosome pathway, but does not degrade WT EGFR. MS9427 has a strong inhibitory effect on NSCLC cell proliferation and can be used in cancer research.

MS9427 TFA is an effective PROTAC EGFR degrader, with Kd values of 7.1 nM and 4.3 nM for wild-type EGFR and mutant EGFR L858R, respectively. MS9427 TFA selectively degrades mutant variants through the ubiquitin/proteasome system (UPS) and autophagy/lysosome pathway, but not WT EGFR. MS9427 TFA strongly inhibits NSCLC cell proliferation and can be used in cancer research.

PP-C8 is an effective selective PROTAC CDK12-Cyclin K degrader. PP-C8 induces degradation of CDK12-Cyclin K with DC50 values of 416 and 412 nM, respectively. PP-C8 exhibits highly efficient synergistic anti-proliferative effects with PARP inhibitors in triple-negative breast cancer (TNBC).

MTX-23 is an AR-based PROTAC. MTX-23 inhibits CaP cell proliferation by degrading AR-V7 and AR-FL. MTX-23 induces apoptosis in cells.

PROTAC BRD4 Degrader-11 (compound 9a) is an effective PROTAC that links von Hippel-Lindau ligand and BRD4 ligand. PROTAC BRD4 Degrader-11 can be coupled with STEAP1 and CLL1 antibodies to degrade the BRD4 protein in PC3 prostate cancer cells, with DC50 values of 0.23 nM and 0.38 nM, respectively.

PROTAC BRD9 Degrader-4 is a dual-function degrader of BRD9, which is being studied for cancer research.

PROTAC CDK12/13 Degrader-1 (7f) TFA is a highly efficient and selective dual degrader of cell cycle-dependent kinases CDK12/CDK13, with DC50 values of 2.2 nM and 2.1 nM, respectively. PROTAC CDK12/13 Degrader-1 TFA has anti-proliferative activity and can be used for research on breast cancer.

PROTAC CYP1B1 degrader-1 (Compound 6C) is an α-naphthoflavone derivative that can eliminate drug resistance mediated by cytochrome P450 (CYP)1B1 by targeting and degrading it. Its IC50 values for CYP1B1 and CYP1A2 are 95.1 and 9838.6 nM, respectively. PROTAC CYP1B1 Degrader-1 can be used to study prostate cancer with overexpression of CYP1B1.

PROTAC IRAK3 degrade-1 (compound 23) formic acid is an effective and selective IRAK3 degrader (IC50 = 5 nM).

SS47 TFA is a PROTAC-based HPK1 degrader that can induce proteasome-mediated degradation of HPK1. SS47 TFA degrades HPK1 and significantly enhances the in vivo anti-tumor efficacy of BCMA CAR-T cell research. HPK1 is an immune-suppressive regulatory kinase and a potential target for cancer immunotherapy.

YX-2-107 is a selective degrader of CDK6 using PROTAC technology (IC50= 4.4 nM). In vitro, YX-2-107 effectively inhibits RB phosphorylation and FOXM1 expression, and suppresses the development of Ph+ ALL in rats. YX-2-107 can be used for research on Ph chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

HDAC6 degrader-1 is a PROTAC that comprises a selective HDAC6 inhibitor Nexturastat A (Nex A) as the HDAC6 binder, a linker and a ligand for recruiting E3 ligase.

PROTAC PTPN2 degrader-1 (compound example 77) is a potent PTPN2 degrader.