THERAPEUTIC MOTS-C RELATED PEPTIDESProvided herein are peptides and peptide analogs and methods of treating a metabolic disease, e.g., obesity, diabetes, methods of treating cancer, methods of treating a liver disease, and methods of modulating fatty acid metabolism.A peptide comprising an amino acid sequence of formula I X1-QE-X2-X3-YI-X4-Y-X5-R-X6 (I) (SEQ ID NO: 1) wherein X1 is absent or if present is X7-RW, wherein X7 is absent or if present is an amino acid with a non-polar side chain or a polar side chain; X2 and X3 are each independently an amino acid with a non-polar side chain or a polar side chain; X4 and X5 are each independently an amino acid with a non-polar side chain; X6 is absent or if present is KL-X8 or X9-LR, wherein X8 is absent or if present is an amino acid with a non-polar side chain and X9 is an amino acid with a non-polar side chain; or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereofwherein the peptide is not a peptide consisting of any one of the amino acid sequences of SEQ ID NOs: 2, 42, 77, 78, 316-318, and 328-349. 2. The peptide of claim 1 wherein X1 is absent or if present is X7-RW, wherein X7 is absent or if present is selected from D, (dD), E, (dE), K, (dK), R, (dR), H, (dH), N, (dN), Q, (dQ), S, (dS), T, (dT), Y, (dY), C, (dC), G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM); X2 and X3 are each independently selected from D, (dD), E, (dE), K, (dK), R, (dR), H, (dH), N, (dN), Q, (dQ), S, (dS), T, (dT), Y, (dY), C, (dC), G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM); X4 and X5 are each independently selected from G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM); X6 is absent or if present is KL-X8 or X9-LR, wherein X8 is absent or if present is selected from G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM) and X9 is selected from G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM); or pharmaceutically acceptable salts thereof. 3. The peptide of claim 1 wherein X1 is absent or if present is X7-RW, wherein X7 is absent or if present is M or E; X2 is M, A or E; X3 is G, N or Q; X4 is F or A; X5 is P or A; X6 is absent or if present is KL-X8 or X9-LR, wherein X8 is absent or if present is R or A and X9 is selected from K, A, (dA), N and Q; or pharmaceutically acceptable salts thereof. 4. The peptide of claim 1 selected from the group consisting of: MRWQEMNYIFYPR (SEQ ID NO: 208);MRWQEAGYIFYPRKLR (SEQ ID NO: 11);MRWQEMGYIFYPR(dA)LR (SEQ ID NO: 149);MRWQEMGYIFYPRNLR (SEQ ID NO: 213);MRWQEMQYIFYPRALR (SEQ ID NO: 219);RWQEMNYIFYPR (SEQ ID NO: 248);MRWQEMGYIFYPRALR (SEQ ID NO: 19);MRWQEMGYIFYPRKLA (SEQ ID NO: 21);MRWQEMGYIFYARKLR (SEQ ID NO: 17);RWQEMGYIFYPRQLR (SEQ ID NO: 217);MRWQEEGYIFYPRKLR (SEQ ID NO: 172);MRWQEMGYIFYPRKL (SEQ ID NO: 45);ERWQEAGYIAYPR (SEQ ID NO: 241);RWQEMQYIFYPR (SEQ ID NO: 211);MRWQEMGYIFYPAKLR (SEQ ID NO: 18);or pharmaceutically acceptable salts thereof. 5. An isolated peptide comprising an amino acid sequence of formula I X1-QE-X2-X3-YI-X4-Y-X5-R-X6 (I)wherein X1 is absent or if present is X7-RW, wherein X7 is absent or if present is an amino acid with a non-polar side chain or a polar side chain; X2 and X3 are each independently an amino acid with a non-polar side chain or a polar side chain; X4 and X5 are each independently an amino acid with a non-polar side chain; X6 is absent or if present is KL-X8 or X9-LR, wherein X8 is absent or if present is an amino acid with a non-polar side chain and X9 is an amino acid with a non-polar side chain; or pharmaceutically acceptable salts thereof; wherein the peptide is not a peptide consisting of any one of the amino acid sequences of SEQ ID NOs : 2, 42, 77, 78, 316-318, and 328-349. 6. The isolated peptide of claim 5 wherein X1 is absent or if present is X7-RW, wherein X7 is absent or if present is selected from D, (dD), E, (dE), K, (dK), R, (dR), H, (dH), N, (dN), Q, (dQ), S, (dS), T, (dT), Y, (dY), C, and (dC), G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM); X2 and X3 are each independently selected from D, (dD), E, (dE), K, (dK), R, (dR), H, (dH), N, (dN), Q, (dQ), S, (dS), T, (dT), Y, (dY), C, and (dC), G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM); X4 and X5 are each independently selected from G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM); X6 is absent or if present is KL-X8 or X9-LR, wherein X8 is absent or if present is selected from G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM) and X9 is selected from G, A, (dA), V, (dV), L, (dL), I, (dI), F, (dF), W, (dW), P (dP), M and (dM); or pharmaceutically acceptable salts thereof. 7. The isolated peptide of claim 5 wherein X1 is absent or if present is X7-RW, wherein X7 is absent or if present is M or E; X2 is M, A or E; X3 is G, N or Q; X4 is F or A; X5 is P or A; X6 is absent or if present is KL-X8 or X9-LR, wherein X8 is absent or if present is R or A and X9 is selected from K, A, (dA), N and Q; or pharmaceutically acceptable salts thereof. 8. The isolated peptide of Claim 5 selected from MRWQEMNYIFYPR (SEQ ID NO...
치료적 MOTS-C 관련 펩타이드펩타이드 및 펩타이드 유사체 및 대사 질환, 예를 들어, 비만, 당뇨병을 치료하는 방법, 암을 치료하는 방법, 간 질환을 치료하는 방법, 및 지방산 대사를 조절하는 방법이 본 명세서에 제공된다.식 I의 아미노산 서열을 포함하는 펩타이드 또는 이의 C-말단 산 또는 아미드, 또는 N-아세틸 유도체; 또는 그의 약제학적으로 허용가능한 염: X1-QE-X2-X3-YI-X4-Y-X5-R-X6 (I) (서열번호: 1)식 중, X1이, 부재이거나 존재하면, X7-RW이고, 상기 X7이, 부재이거나 존재하면, 무극성 측쇄 또는 극성 측쇄를 가지고 있는 아미노산이고; X2 및 X3 각각은 독립적으로 무극성 측쇄 또는 극성 측쇄를 가지고 있는 아미노산이고; X4 및 X5 각각은 독립적으로 무극성 측쇄를 가지고 있는 아미노산이고; X6이, 부재이거나 존재하면, KL-X8 또는 X9-LR이고, 상기 X8이, 부재이거나 존재하면, 무극성 측쇄를 가지고 있는 아미노산이고, 그리고 X9는 무극성 측쇄를 가지고 있는 아미노산이고; 상기 펩타이드는 서열번호: 2, 42, 77, 78, 316-318, 및 328-349의 아미노산 서열 중 임의의 하나로 구성된 펩타이드가 아니다.