AU-15330

• CAT Number: I045142
• CAS Number: 2380274-50-8
• Molecular Formula: C39H49N9O5S
• Molecular Weight: 755.93
• Purity: ≥95%
• Synonyms: (2S,4R)-1-[(2S)-2-[[2-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
• InChI: InChI=1S/C39H49N9O5S/c1-23(25-10-12-26(13-11-25)34-24(2)41-22-54-34)42-37(52)31-18-27(49)20-48(31)38(53)35(39(3,4)5)43-33(51)21-46-14-16-47(17-15-46)30-19-29(44-45-36(30)40)28-8-6-7-9-32(28)50/h6-13,19,22-23,27,31,35,49-50H,14-18,20-21H2,1-5H3,(H2,40,45)(H,42,52)(H,43,51)/t23-,27+,31-,35+/m0/s1
• InChIKey: HDCCMCFIGHIDJR-TUDDPRDOSA-N
• SMILES: CC1=C(SC=N1)C2=CC=C(C=C2)C(C)NC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CN4CCN(CC4)C5=CC(=NN=C5N)C6=CC=CC=C6O)O

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].
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].

Reference

[1]. Xiao L, et al. Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer. Nature. 2022;601(7893):434-439.
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