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1. WO2020141704 - PEPTIDE INHIBITORY OF TLR4 SIGNALING AND USE THEREOF

Publication Number WO/2020/141704
Publication Date 09.07.2020
International Application No. PCT/KR2019/014195
International Filing Date 25.10.2019
IPC
C07K 7/06 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
7Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
04Linear peptides containing only normal peptide links
06having 5 to 11 amino acids
A61P 29/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29Non-central analgesic, antipyretic or antiinflammatory agents, e.g antirheumatic agents; Non-steroidal antiinflammatory drugs (NSAIDs)
A61P 37/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37Drugs for immunological or allergic disorders
A61K 38/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
CPC
A61K 38/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
A61P 29/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29Non-central analgesic, antipyretic or anti-inflammatory agents, e.g antirheumatic agents; Non-steroidal anti-inflammatory drugs (NSAIDs)
A61P 37/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37Drugs for immunological or allergic disorders
C07K 7/06
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
7Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
04Linear peptides containing only normal peptide links
06having 5 to 11 amino acids
Applicants
  • 주식회사 젠센 GENESEN CO., LTD. [KR]/[KR]
Inventors
  • 최상돈 CHOI, Sangdun
  • 아첵아스마 ACHEK, Asma
Agents
  • 제일특허법인(유) FIRSTLAW P.C.
Priority Data
10-2019-000063003.01.2019KR
Publication Language Korean (KO)
Filing Language Korean (KO)
Designated States
Title
(EN) PEPTIDE INHIBITORY OF TLR4 SIGNALING AND USE THEREOF
(FR) PEPTIDE INHIBITEUR DE LA SIGNALISATION TLR4 ET UTILISATION ASSOCIÉE
(KO) TLR4 신호전달 경로를 억제하는 펩타이드 및 그 용도
Abstract
(EN)
The present invention relates to a peptide that inhibits toll-like receptor 4 (TLR4) signaling and, more particularly, to a peptide that binds to the TIR domain of TLR4 to suppress the secretion of pre-inflammatory cytokines and inhibit the activation of NF-κB and MAPKs, a fusion peptide in which the peptide is fused to a cell-penetrating peptide, a TLR4 antagonist comprising the peptide or fusion peptide, and a composition comprising the peptide or fusion peptide for preventing or treating an autoimmune disease or an inflammatory disease. The peptide according to the present invention exhibits an inhibitory effect on TLR4 and TLR3 signaling, blocks MyD88- and TRIF-dependent TLR4-signaling pathway in various humans and murine cell lines, and has substantial disease relieving effects in rheumatoid arthritis, psoriasis, and systemic lupus erythematosus mouse models. Thus, the peptide can be used as a therapeutic agent for immune-related diseases requiring the negative control of TLR for the therapy thereof.
(FR)
La présente invention concerne un peptide permettant d'inhiber la signalisation du récepteur de type Toll 4 (TLR4) et, plus particulièrement, un peptide qui se lie au domaine TIR de TLR4 pour supprimer la sécrétion de cytokines pré-inflammatoires et inhiber l'activation de NF-κB et de MAPK, un peptide de fusion dans lequel le peptide est fusionné à un peptide de pénétration cellulaire, un antagoniste de TLR4 comprenant le peptide ou le peptide de fusion, et une composition comprenant le peptide ou le peptide de fusion pour prévenir ou traiter une maladie auto-immune ou une maladie inflammatoire. Le peptide selon la présente invention a un effet inhibiteur sur la signalisation de TLR4 et de TLR3, bloque la voie de signalisation de TLR4 dépendante de MyD88 et TRIF dans plusieurs lignées cellulaires humaines et de souris, et a des effets importants de soulagement de maladie dans la polyarthrite rhumatoïde, le psoriasis et des modèles de souris de lupus érythémateux disséminé. Ainsi, le peptide peut être utilisé en tant qu'agent thérapeutique pour des maladies liées au système immunitaire nécessitant un contrôle négatif du TLR pour sa thérapie.
(KO)
본 발명은 TLR4(Toll-like receptor 4) 신호전달 경로를 억제하는 펩타이드에 관한 것으로, 더욱 상세하게는 TLR4의 TIR 도메인에 결합하여 전염증성 사이토카인의 분비를 억제하고, NF-κB와 MAPKs의 활성화를 억제하는 펩타이드, 상기 펩타이드에 세포 투과성 펩타이드가 결합된 융합 펩타이드, 상기 펩타이드 또는 융합 펩타이드를 포함하는 TLR4 길항제 및 상기 펩타이드 또는 융합 펩타이드를 포함하는 자가면역 질환 또는 염증성 질환의 예방 또는 치료용 조성물에 관한 것이다. 본 발명에 따른 펩타이드는 TLR4 및 TLR3 신호전달에 억제 효과를 나타내며, 다수의 인간 및 쥐 세포주에서 MyD88- 및 TRIF-의존적 TLR4-경로를 차단하고, 류마티스 관절염, 건선 및 전신홍반루푸스 마우스 모델에서 실질적인 질병 완화 효과를 가지므로, TLR의 음성 조절이 요구되는 면역 관련 질환의 치료제로서 활용할 수 있다.
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