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. 2022 Sep 1;14(19):1403–1416. doi: 10.4155/fmc-2022-0149

Table 1. . Protease-targeted chimera molecules under clinical development.

PROTAC/structure E3 ligase & target Condition Company Administration route Phase Status/NCT no. Ref.
graphic file with name fmc-14-1403-T1a.jpg E3 ligase: CRBN
Target: AR		 Prostate cancer, metastatic Arvinas Oral Phase II Recruiting/ NCT03888612 [18]
graphic file with name fmc-14-1403-T1b.jpg E3 ligase: CRBN
Target: ER		 Breast cancer Arvinas/Pfizer Oral Phase II Recruiting/ NCT04072952 [19]
graphic file with name fmc-14-1403-T1c.jpg E3 ligase: VHL
Target: AR		 Prostate cancer, metastatic Arvinas Androgen Receptor, Inc. Oral Phase I Recruiting/ NCT05067140 [20]
graphic file with name fmc-14-1403-T1d.jpg E3 ligase: VHL
Target: BCL-XL 		Solid tumor and hematologic malignancy Dialectic Therapeutics, Inc Intravenous Phase I Recruiting/ NCT04886622 [21]
graphic file with name fmc-14-1403-T1e.jpg E3 ligase: CRBN
Target: IRAK4		 Atopic dermatitis and hidradenitis suppurativa Kymera Therapeutics, Inc. Oral Phase I Recruiting/ NCT04772885 [22]
KT-413 E3 ligase: CRBN
Target: IRAK4		 Non-Hodgkin lymphoma and diffuse large B-cell lymphoma Kymera Therapeutics, Inc. Intravenous Phase I Recruiting/ NCT05233033 [23]
KT-333 E3 ligase: Not disclosed
Target: STAT3		 Non-Hodgkin lymphoma, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, large granular lymphocytic leukemia and solid tumors Kymera Therapeutics, Inc. Intravenous Phase I Recruiting/ NCT05225584 [24]
NX-2127 E3 ligase: CRBN
Target: BTK		 Chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenstrom macroglobulinemia, mantle cell lymphoma and follicular lymphoma Nurix Therapeutics, Inc. Oral Phase I Recruiting/ NCT04830137 [25]
NX-5948 E3 ligase: CRBN
Target: BTK		 Chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenstrom macroglobulinemia, mantle cell lymphoma and follicular lymphoma Nurix Therapeutics, Inc. Oral Phase I Recruiting/ NCT05131022 [26]
CFT8634 E3 ligase: CRBN
Target: BRD9		 Synovial sarcoma and soft tissue sarcoma C4 Therapeutics, Inc. Oral Phase II Recruiting/ NCT05355753 [27]
CC-94676 E3 ligase: CRBN
Target: AR		 Prostate cancer, metastatic Celgene Oral Phase I Recruiting/ NCT04428788 [28]
AC682 E3 ligase: CRBN
Target: ER		 Breast cancer Accutar Biotechnology Inc. Oral Phase I Recruiting/ NCT05080842 [29]

AR: Androgen receptor; BCL-XL: B-cell lymphoma, extra large; BRD9: Bromodomain-containing protein 9; BTK: Bruton's tyrosine kinase; CRBN: Cereblon protein, ER: Endoplasmic reticulum protein; IRAK: IL-1 receptor-associated kinase; NCT: National clinical trial; PROTAC: Protease-targeted chimera; STAT3: Signal transducer and activator of transcription 3; VHL: von Hippel–Lindau tumor suppressor protein.