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    DRUG:

    AU-15330

    i
    Other names: AU-15330
    Associations

    News

    Trials
    Company:
    Dr. Reddy’s
    Drug class:
    SMARCA2 degrader, SMARCA4 degrader
    Related drugs:
    Associations

    News

    Trials
    23d
    Chromatin Helicase CHD6 Establishes Pro-inflammatory Enhancers and is a Synthetic Lethal Target in FH-Deficient Renal Cell Carcinoma. (PubMed, Cancer Res)
    The PROTAC degrader of SMARCA2/4 AU-15330 effectively abolished structures of cis-regulatory elements bound by CHD6 and suppressed the growth of FH-mutated, but not FH-intact, RCC in vivo. Collectively, these data indicate that CHD6 is a molecular bridge between FH deficiency and pro-inflammatory enhancers assembly that endows FH-deficient tumors with epigenetic vulnerabilities.
    Journal • Synthetic lethality
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    KEAP1 (Kelch Like ECH Associated Protein 1) • FH (Fumarate Hydratase) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • CHD6 (Chromodomain Helicase DNA Binding Protein 6)
    |
    AU-15330
    over1year
    Targeting SWI/SNF ATPases in H3.3K27M diffuse intrinsic pontine gliomas. (PubMed, Proc Natl Acad Sci U S A)
    The proteolysis targeting chimera (PROTAC) AU-15330 that simultaneously targets SMARCA4, SMARCA2, and PBRM1 for degradation exhibits cytotoxicity in H3.3K27M but not H3 wild-type cells...Moreover, genetic or pharmacologic targeting of FOXO1 resulted in cell death in H3K27M cells. Overall, our results suggest that H3K27M up-regulates SMARCA4 levels and combined targeting of SWI/SNF ATPases in H3.3K27M can serve as a potent therapeutic strategy for these deadly childhood brain tumors.
    Journal
    |
    PBRM1 (Polybromo 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FOXO1 (Forkhead box O1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    PBRM1 mutation • SMARCA4 mutation • H3.3K27M
    |
    AU-15330
    almost2years
    Overcoming acquired resistance to PROTAC degraders (AACR 2023)
    Our study found that the mechanisms of resistance of PROTAC degraders can vary and may be dependent on drug concentrations. Such concepts may inform future clinical decision-making regarding drug dosing.
    Preclinical
    |
    PBRM1 (Polybromo 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ABCC1 (ATP Binding Cassette Subfamily C Member 1)
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    ABCB1 overexpression • ABCB1 expression • ABCC1 expression
    |
    AU-15330