| Description |
AU-15330 is a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide. AU-15330 induces disease remission in castration-resistant prostate cancer (CRPC) models without toxicity[1].
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| Related Catalog |
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| Target |
SMARCA2 and SMARCA4[1]
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| In Vivo |
AU-15330 (10 and 30 mg/kg; i.v.; 5 days per week for 3 weeks) shows no evident toxicity in immuno-competent mice[1]. AU-15330 (60 mg/kg with or without 10 mg/kg enzalutamide; i.v.; 3 days per week; p.o.; 5 days per week for 5 weeks) leads to potent inhibition of tumour growth, triggering disease regression in more than 20% of animals. Combinatorial regimen induced the most potent anti-tumour effect, with regression in all animals[1]. AU-15330 (60 mg/kg with or without 10 mg/kg enzalutamide; i.v.; 3 days per week; p.o.; 5 days per week for 5 weeks) strongly inhibits the growth of C4-2B cell line-derived CRPC xenografts in intact mice as a single agent and synergized with enzalutamide[1]. AU-15330 (60 mg/kg with or without 10 mg/kg enzalutamide; i.v.; 3 days per week; p.o.; 5 days per week for 5 weeks) combines with enzalutamide induces significant tumour growth inhibition, causing regression in more than 30% of animals in the modle of CRPC variant of the MDA-PCa-146-12 PDX by tumour implantation into castrated mice[1]. Animal Model: Six-week-old male CB17 severe combined immunodeficiency (SCID) mice[1] Dosage: 10 and 30 mg/kg Administration: i.v. (5 days per week for 3 weeks) Result: Showed no evident toxicity in immuno-competent mice. Animal Model: VCaP castration-resistant tumour model (six-week-old male CB17 severe combined immunodeficiency (SCID) mice)[1] Dosage: 60 mg/kg with or without 10 mg/kg enzalutamide Administration: i.v. (3 days per week); p.o. (5 days per week for 5 weeks) Result: Resulted inhibition of tumor growth and triggered disease regression in more than 20% of animals. Combinatorial regimen induced the most potent anti-tumour effect, with regression in all animals. Animal Model: C4-2B non-castrated tumour model (six-week-old male CB17 severe combined immunodeficiency (SCID) mice)[1] Dosage: 60 mg/kg with or without 30 mg/kg enzalutamide Administration: i.v. (3 days per week); p.o. (5 days per week for 4 weeks) Result: Strongly inhibited the growth of C4-2B cell line-derived CRPC xenografts in intact mice as a single agent and synergized with enzalutamide.
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| References |
[1]. Xiao L, et al. Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer. Nature. 2022;601(7893):434-439.
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