ArticleBlood2023
The orally bioavailable GSPT1/2 degrader SJ6986 exhibits in vivo efficacy in acute lymphoblastic leukemia.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting the epigenome and the integrated stress response to normalize colorectal cancer subclonal plasticity and progression.Cell death & disease · 2026Article
- Advances in molecular glue degraders for targeted protein degradation: Focus on NEK7, WEE1, CDK2, GSPT1 and VAV1.Asian journal of pharmaceutical sciences · 2026Review
- Cancer Biology of GSPT1: Mechanisms and Targeted Therapy Opportunities of Molecular Glue Degraders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Targeting of IRAK4 and GSPT1 enhances therapeutic efficacy in AML via c-Myc destabilization.Leukemia · 2025Article
- Unbiased mapping of cereblon neosubstrate landscape by high-throughput proteomics.Nature communications · 2025Article
- High cereblon expression in neuroendocrine cancer confers vulnerability to GSPT1 molecular glue degrader.Experimental hematology & oncology · 2025Article
- Integrated Computational Analysis Reveals Early Genetic and Epigenetic AML Susceptibility Biomarkers in Benzene-Exposed Workers.International journal of molecular sciences · 2025Article
- Fluorinated small molecule derivatives in cancer immunotherapy: emerging frontiers and therapeutic potential.Frontiers in immunology · 2025Review
- Discovery of CRBN-Dependent WEE1 Molecular Glue Degraders from a Multicomponent Combinatorial Library.Journal of the American Chemical Society · 2024Article
- Biologic and Clinical Analysis of Childhood Gamma Delta T-ALL Identifies LMO2/STAG2 Rearrangements as Extremely High Risk.Cancer discovery · 2024Article
- Targeted protein degradation in hematologic malignancies: clinical progression towards novel therapeutics.Biomarker research · 2024Review
- Potential of GSPT1 as a novel target for glioblastoma therapy.Cell death & disease · 2024Article
- Article
- Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines.Nature communications · 2024Article
- Direct-to-biology, automated, nano-scale synthesis, and phenotypic screening-enabled E3 ligase modulator discovery.Nature communications · 2023Article
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Advancing cure rates for high-risk acute lymphoblastic leukemia (ALL) has been limited by the lack of agents that effectively kill leukemic cells, sparing normal hematopoietic tissue. Molecular glues direct the ubiquitin ligase cellular machinery to target neosubstrates for protein degradation. We developed a novel cereblon modulator, SJ6986, that exhibits potent and selective degradation of GSPT1 and GSPT2 and cytotoxic activity against childhood cancer cell lines. Here, we report in vitro and in vivo testing of the activity of this agent in a panel of ALL cell lines and xenografts. SJ6986 exhibited similar cytotoxicity to the previously described GSPT1 degrader CC-90009 in a panel of leukemia cell lines in vitro, resulting in apoptosis and perturbation of cell cycle progression. SJ6986 was more effective than CC-90009 in suppressing leukemic cell growth in vivo, partly attributable to favorable pharmacokinetic properties, and did not significantly impair differentiation of human CD34+ cells ex vivo. Genome-wide CRISPR/Cas9 screening of ALL cell lines treated with SJ6986 confirmed that components of the CRL4CRBN complex, associated adaptors, regulators, and effectors were integral in mediating the action of SJ6986. SJ6986 is a potent, selective, orally bioavailable GSPT1/2 degrader that shows broad antileukemic activity and has potential for clinical development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.