di-Ellipticine-RIBOTAC TFA 

di-Ellipticine-RIBOTAC TFA is a RNase recruiting chimera (RIBOTAC) degrader, capable of specifically binding and degrading expanded G4C2 RNA repeat (r(G₄C₂)^exp). di-Ellipticine-RIBOTAC TFA selectively binds the three-dimensional (3D) structure formed by r(G₄C₂)^exp and that recruits an endogenous ribonuclease (RNase) to cleave r(G₄C₂)^exp. di-Ellipticine-RIBOTAC TFA selectively degrades the mutant chromosome 9 open reading frame 72 (C9orf72) allele and reduces quantities of toxic dipeptide repeat proteins (DPRs) translated from r(G₄C₂)^exp. di-Ellipticine-RIBOTAC TFA significantly improves the pathological phenotype of amyotrophic lateral sclerosis/ frontotemporal dementia (c9ALS/FTD) in cells and mouse models. di-Ellipticine-RIBOTAC TFA can be used for the study of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)^[1].

di-Ellipticine-RIBOTAC (compound 7) (5-500 nM) TFA inhibits RAN translation of r(G₄C₂)66 in HEK293T cells, and reduces quantities of the r(G₄C₂)^exp-containing transcript in a dose-dependent fashion^[1].
di-Ellipticine-RIBOTAC (5-500 nM) TFA selectively reduces C9orf72 intron 1 abundance with an IC₅₀ of ~50 nM. di-Ellipticine-RIBOTAC TFA also reduces poly(GP) abundance in c9ALS patient-derived lymphoblastoid cell lines (LCLs) and c9ALS patient-derived induced pluripotent stem cells (iPSCs)^[1].
di-Ellipticine-RIBOTAC (50 nM; 2.5 weeks) TFA reduces C9orf72 transcripts containing the r(G₄C₂)^exp repeat in intron 1 in iPSC-derived spinal motor neurons (iPSNs) from c9ALS patients and reversed the loss of Nup98^[1].
di-Ellipticine-RIBOTAC TFA cleaves Cy5- and Cy3-labeled r(G₄C₂)₈ RNA in the presence of RNase L^[1].
di-Ellipticine-RIBOTAC TFA inhibits hnRNP H1 binding to r(G₄C₂)₈ RNA (IC₅₀ = 2.4 μM)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

di-Ellipticine-RIBOTAC (compound 7) (33 nmol; i.c.v.; single dose) TFA reduces c9ALS/FTD pathology in a C9orf72 bacterial artificial chromosome (BAC) mouse model (+/+PWR500^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1524.65

C₈₀H₈₈F₃N₇O₁₈S

2767983-77-5

CCOC(C1=C(S/C(C1=O)=C\C2=CC=C(C(O)=C2)OCCOCCOCCOCCNC(CCC(N(CCOCCOCCOC3=CC4=C(NC5=C4C(C)=C6C=NC=CC6=C5C)C=C3)CCOCCOCCOC7=CC=C8NC9=C(C(C)=C%10C=NC=CC%10=C9C)C8=C7)=O)=O)NC%11=CC=CC=C%11)=O.OC(C(F)(F)F)=O

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Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Bush JA, et al. Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G4C2) repeat expansion in vitro and in vivo ALS models. Sci Transl Med. 2021 Oct 27;13(617):eabd5991.  [Content Brief]