Compositions and methods for deinhibiting RE1 silencing transcription factor target genes

• Main Authors: NESTI, EDMUND, PISARCHIK, ALEXANDER
• Format: Patent
• Language: Chinese; English
• Published: 06.09.2022
• Subjects: CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES

The present invention relates to compounds, compositions and methods for deinhibiting a RE1 silencing transcription factor (REST) target gene. In particular, disclosed is a peptide having the sequences TEDLEPPEPPLPKIN (SEQ ID NO: 1) and EDLEPPEPPLPK (SEQ ID NO: 15) or a reverse sequence (reverse inverted (RI)) consisting of D-amino acids nekplppeppeldet (SEQ ID NO: 16) and kplppeppeldet (SEQ ID NO: 17), for use in the inhibition of REST activity. The peptides can be used for treating, preventing or alleviating diseases such as traumatic brain injury, epilepsy, dementia, Huntington's disease (HD), chronic pain, brain cancer (including glioblastoma multiforme), pancreatic cancer, diabetes and peripheral nerve injury. 本发明涉及用于去抑制RE1沉默转录因子(REST)靶基因的化合物、组合物和方法。具体而言，公开了具有序列TEDLEPPEPPLPKEN(SEQIDNO：1)和EDLEPPEPPLPK(SEQIDNO：15)或由D-氨基酸nekplppeppeldet(SEQIDNO：16)和kplppeppelde(SEQIDNO：17)组成的反向序列(反向倒置(retroinverted)，RI)的肽，用于抑制REST活性。这些肽可用于治疗、预防或缓解创伤性脑损伤、癫痫、痴呆、亨廷顿病(HD)、慢性疼痛、脑癌(包括多形性胶质母细胞瘤)、胰腺癌、糖尿病和周围神经损伤等疾病。