Eukaryotic Release Factor (eRF)
Eukaryotic release factors terminate protein biosynthesis by recognizing stop codons and promoting peptidyl-tRNA hydrolysis on the ribosome[1][2]. Mechanistically, eRF1 recognizes UAA, UAG, and UGA stop codons, whereas eRF3 acts as a GTPase that cooperates with eRF1 to accelerate nascent polypeptide release[2][3]. In mRNA quality control, eRF1 and eRF3 also participate in the SMG1-UPF1-eRF1-eRF3 SURF complex that links translation termination to nonsense-mediated mRNA decay[4]. In disease models, premature termination codon readthrough provides an experimental route for studying nonsense-mutation disorders, and eRF3 degradation enhances G418-induced readthrough while altering NMD-related protein levels[5]. Compared with eRF3b, eRF3a silencing markedly increases premature nonsense codon readthrough in human cells, while eRF3b overexpression compensates for termination defects caused by eRF3a depletion[6]. Therefore, eRF3a and eRF3b are not fully equivalent release-factor isoforms, because eRF3a mainly maintains mammalian termination-complex formation and eRF1 stability[6]. For experimental applications, eRF3a degraders including CC-90009, CC-885, and SJ6986 support studies of premature stop codon readthrough and CFTR nonsense-mutation rescue[5][7].eRF research connects translation termination, stop codon recognition, GTP hydrolysis, and nonsense-mediated decay.
eRF3a and eRF3b isoform differences guide mammalian termination-complex and readthrough experiments.
eRF3a degraders support CFTR nonsense mutation rescue and premature stop codon readthrough studies.
References:
- [1]. Song H, et al. The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis. Cell. 2000;100(3):311-321. [Content Brief]
- [2]. Alkalaeva EZ, et al. In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell. 2006;125(6):1125-1136. [Content Brief]
- [3]. Cheng Z, et al. Structural insights into eRF3 and stop codon recognition by eRF1. Genes Dev. 2009;23(9):1106-1118. [Content Brief]
- [4]. Kashima I, et al. Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. Genes Dev. 2006;20(3):355-367. [Content Brief]
- [5]. Baradaran-Heravi A, et al. Effect of small molecule eRF3 degraders on premature termination codon readthrough. Nucleic Acids Res. 2021;49(7):3692-3708. [Content Brief]
- [6]. Chauvin C, et al. Involvement of human release factors eRF3a and eRF3b in translation termination and regulation of the termination complex formation. Mol Cell Biol. 2005;25(14):5801-5811. [Content Brief]
- [7]. Lee RE, et al. Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough. J Clin Invest. 2022;132(18):e154571. [Content Brief]
Eukaryotic Release Factor (eRF) Isoform Specific Products
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Eukaryotic Release Factor (eRF) Related Products (59)
Related Products (59)
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Eukaryotic Release Factor (eRF) Isoform Comparison
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PROTAC FLT-3 degrader 5
0 ImagesCat. No.: HY-175040PROTAC FLT-3 degrader 5 is an orally active FLT3 PROTAC degrader with a DC50 of 1.2 nM. PROTAC FLT-3 degrader 5 also acts as a molecular glue to degrade GSPT1 and IKZF1/3, with DC50 values of 8.54 nM, 0.02 nM and 0.79 nM, respectively. PROTAC FLT-3 degrader 5 mediates the degradation of FLT3, GSPT1 and IKZF1/3 through interaction with the cereblon E3 ubiquitin ligase complex. PROTAC FLT-3 degrader 5 can be used in the research of acute myeloid leukemia.
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GSPT1 degrader-17
0 ImagesCat. No.: HY-177766GSPT1 degrader-17 is a selective GSPT1 molecular glue degrader with a DC50 of 35 nM. GSPT1 degrader-17 induces GSPT1 degradation via the ubiquitin-proteasome system, which leads to G0/G1 phase cell cycle arrest and triggers apoptosis, thereby inhibiting the proliferation of leukemia cells. GSPT1 degrader-17 can be used in leukemia research.
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DHC-286
0 ImagesDHC-286 is a molecular glue degrader targeting GSPT1. DHC-286 recruits GSPT1 to the CRL4CRBN ubiquitin ligase complex, promoting GSPT1 ubiquitination and proteasomal degradation, inducing cytotoxicity. DHC-286 is promising for research of cancers such as acute myeloid leukemia.
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Lenalidomide 4'CH2NH2, 6'F
0 ImagesCat. No.: HY-W882406CAS No.: 2813335-37-2Lenalidomide 4'CH2NH2, 6'F is a molecular glue degrader targeting GSPT1 protein. Lenalidomide 4'CH2NH2, 6'F modulates ubiquitin E3 ligase activity and shifts substrate specificity, resulting in altered substrate degradation. Lenalidomide 4'CH2NH2, 6'F inhibits cancer cell proliferation. Lenalidomide 4'CH2NH2, 6'F can be used in research related to acute myeloid leukemia.
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GSPT1 degrader-11
0 ImagesCat. No.: HY-177724GSPT1 degrader-11 is a CRBN-dependent molecular glue degrader targeting GSPT1, with a DC50 of 67.7 nM. GSPT1 degrader-11 induces CRBN-dependent degradation of GSPT1 via the ubiquitin-proteasome pathway. GSPT1 degrader-11 exhibits CRBN-dependent growth inhibitory activity in cancer cells. GSPT1 degrader-11 can be used for the research of triple-negative breast cancer.
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YB-3-17
0 ImagesYB-3-17 is a blood-brain barrier permeable mTOR inhibitor (IC50 = 0.22 nM) and GSPT1 PROTAC degrader. YB-3-17 inhibits mTORC1/2, CK1δ/ε, mutant ALK and HER2 kinases, induces CRBN-dependent selective GSPT1 degradation, ablates mTOR downstream phosphorylation, downregulates c-Myc/Cyclin D1 to impair tumor translation, triggers p53-mediated apoptosis, suppresses tumor proliferation and xenograft tumor growth, and can be used for the study of glioma, neuroblastoma, breast cancer, lymphoma, colorectal cancer and lung cancer.
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GSPT1 degrader-6
0 ImagesCat. No.: HY-162535CAS No.: 3034764-41-2GSPT1 degrader-6 is a GSPT1 molecular glue degrader that recruits cereblon (CRBN), with a DC50 of 13 nM. GSPT1 degrader-6 induces GSPT1 protein degradation via the ubiquitin-proteasome pathway. GSPT1 degrader-6 can be used in breast cancer-related research.
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GSPT1 degrader-9
0 ImagesCat. No.: HY-159609CAS No.: 3034310-17-0GSPT1 degrader-9 (Compound F) is a cereblon-based molecular glue degrader for G1 to S phase transition protein 1 (GSPT1) that degrades GSPT1 with a rate of 95% (1 μM) GSPT1 and 86% (0.1 μM). GSPT1 degrader-9 inhibits the cell viability of HL-60 with an IC50 of 9.2 nM.
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WB156
0 ImagesCat. No.: HY-174266CAS No.: 2368944-44-7WB156 is a dual MDM2 and GSPT1 PROTAC degrader with a DC50 of 23 nM against MDM2. WB156 induces the degradation of MDM2 and GSPT1 via the ubiquitin-proteasome system. WB156 upregulates the levels of p53 and p21, and triggers Apoptosis through the cleavage of PARP and Caspase-3. WB156 can be used in leukemia-related research.
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ABS-752
0 ImagesCat. No.: HY-W599279CAS No.: 2761170-84-5ABS-752 is an orally active prodrug targeting CRBN-modulating molecular glue with selectivity in protein degradation. ABS-752 preferentially degrades GSPT1 and induces cytotoxicity through this degradation, while it also degrades NEK7, SALL4 and CK1α, with weaker degradation potency against CK1α. As a prodrug, ABS-752 requires metabolic activation to ABT-002 to form the active complex; VAP-1 mediates its conversion to an aldehyde intermediate. ABS-752 induces cell death, reduces cell viability, and exhibits antitumor activity, leading to regression and inhibition of tumor growth. ABS-752 shows no cytotoxicity in primary human hepatocytes. ABS-752 can be used in the research of hepatocellular carcinoma.
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GSPT1 degrader-10
0 ImagesCat. No.: HY-159610CAS No.: 3024909-61-0GSPT1 degrader-10 (compound A) is a cereblon-based molecular glue degrader of GSPT1 with more than 95% degradation. GSPT1 degrader-8 inhibits cell viability in HL-60 cells with an IC50 of 10 nM.
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GSPT2 degrader-1
0 ImagesCat. No.: HY-177744CAS No.: 3093413-09-0GSPT2 degrader-1 (compound 619) is a selective molecular glue GSPT2 degrader targeting GSPT2. GSPT2 degrader-1 contains Thalidomide (HY-14658) and the linker of MDEG-541 (HY-150259). GSPT2 degrader-1 induces the degradation, but not GSPT1 or myelocytomatosis oncogene (MYC). GSPT2 degrader-1 can be used for research of gastrointestinal cancer.
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PROTAC erf3a Degrader-2
0 ImagesCat. No.: HY-163938ACAS No.: 3033871-15-4PROTAC erf3a Degrader-2 (Compound C59) is an orally active PROTAC erf3a Degrader. PROTAC erf3a Degrader-2 inhibits protein expression of SRD5A3 and GSPT1(eRF3a). PROTAC erf3a Degrader-2 inhibits cancer cell proliferation (eg: 22Rv1). PROTAC erf3a Degrader-2 can be used for research of prostate cancer, ovarian cancer, liver cancer, cervical cancer, leukemia, breast cancer.
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GSPT1 degrader-18
0 ImagesCat. No.: HY-188006CAS No.: 3052938-18-5GSPT1 degrader-18 is a GSPT1 degrader that inhibits the proliferation of cancer cells. GSPT1 degrader-18 has weak ability to induce the formation of the GSPT1-CRBN/DDB1 ternary complex and belongs to a weak molecular glue. GSPT1 degrader-18 can be used in cancer-related research.
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GSPT1 degrader-7
0 ImagesCat. No.: HY-174238CAS No.: 3082942-43-3GSPT1 degrader-7 (Example 43) is a molecular glue degrader targeting GSPT1. GSPT1 degrader-7 has an EC50 of 0.2 nM in DF15 multiple myeloma cells. GSPT1 degrader-7 can be used in the study of cancer.
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CC-885 (Standard)
0 ImagesCat. No.: HY-101488RCAS No.: 1010100-07-8CC-885 (Standard) is the analytical standard of CC-885 (HY-101488). This product is intended for research and analytical applications. CC-885, a cereblon (CRBN) modulator, acts as a molecular glue degrader targeting GSPT1 with a Kd of 350 nM. CC-885 binds to CRBN to alter the substrate specificity of the CRL4 E3 ligase, promoting the ubiquitination and proteasomal degradation of GSPT1, BNIP3L, PLK1, CDK4, IKZF1/3, GSPT2, WIZ, CHD7, GOLM1, CK1α and ETS1. CC-885 induces apoptosis, cell cycle arrest, transcriptional downregulation and antiproliferation in cancer cells. CC-885 is applicable to research related to relapsed/refractory acute myeloid leukemia, MYC-driven tumors, metastatic castration-resistant prostate cancer, multiple myeloma, hepatocellular carcinoma, glioblastoma, VHL-deficient clear cell renal cell carcinoma and non-small cell lung cancer.
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FL2-14
0 ImagesCat. No.: HY-177777FL2-14 is a CRBN-dependent selective molecular glue degrader of GSPT2. FL2-14 specifically degrades GSPT2 by recruiting the CRBN E3 ligase to recognize the G-loop sequence on the target protein GSPT2. FL2-14 can be used in related research on colorectal cancer.
