KR102761094B1 - 변이체 actriib 단백질 및 이의 용도 - Google Patents
변이체 actriib 단백질 및 이의 용도 Download PDFInfo
- Publication number
- KR102761094B1 KR102761094B1 KR1020237036672A KR20237036672A KR102761094B1 KR 102761094 B1 KR102761094 B1 KR 102761094B1 KR 1020237036672 A KR1020237036672 A KR 1020237036672A KR 20237036672 A KR20237036672 A KR 20237036672A KR 102761094 B1 KR102761094 B1 KR 102761094B1
- Authority
- KR
- South Korea
- Prior art keywords
- amino acid
- seq
- polypeptide
- actriib
- acid sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 title claims abstract 12
- 239000003446 ligand Substances 0.000 claims abstract description 121
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 621
- 235000001014 amino acid Nutrition 0.000 claims description 404
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 306
- 229920001184 polypeptide Polymers 0.000 claims description 288
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 288
- 108020001507 fusion proteins Proteins 0.000 claims description 258
- 102000037865 fusion proteins Human genes 0.000 claims description 258
- 150000001413 amino acids Chemical class 0.000 claims description 170
- 108090000623 proteins and genes Proteins 0.000 claims description 137
- 235000018102 proteins Nutrition 0.000 claims description 126
- 102000004169 proteins and genes Human genes 0.000 claims description 126
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 85
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 84
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 84
- 150000007523 nucleic acids Chemical class 0.000 claims description 77
- 210000004027 cell Anatomy 0.000 claims description 47
- 230000004048 modification Effects 0.000 claims description 41
- 238000012986 modification Methods 0.000 claims description 40
- 230000011664 signaling Effects 0.000 claims description 38
- 239000002773 nucleotide Substances 0.000 claims description 26
- 125000003729 nucleotide group Chemical group 0.000 claims description 26
- 102000039446 nucleic acids Human genes 0.000 claims description 25
- 108020004707 nucleic acids Proteins 0.000 claims description 25
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 24
- 238000006206 glycosylation reaction Methods 0.000 claims description 24
- 239000000710 homodimer Substances 0.000 claims description 24
- 235000013922 glutamic acid Nutrition 0.000 claims description 23
- 239000004220 glutamic acid Substances 0.000 claims description 23
- 230000013595 glycosylation Effects 0.000 claims description 22
- 108010023082 activin A Proteins 0.000 claims description 11
- 102100040898 Growth/differentiation factor 11 Human genes 0.000 claims description 8
- 102100040892 Growth/differentiation factor 2 Human genes 0.000 claims description 8
- 101000893585 Homo sapiens Growth/differentiation factor 2 Proteins 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims description 7
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 6
- 201000000585 muscular atrophy Diseases 0.000 claims description 6
- 238000000423 cell based assay Methods 0.000 claims description 5
- 101000893545 Homo sapiens Growth/differentiation factor 11 Proteins 0.000 claims description 4
- 201000006938 muscular dystrophy Diseases 0.000 claims description 4
- 201000006935 Becker muscular dystrophy Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 230000003389 potentiating effect Effects 0.000 claims description 2
- 239000013598 vector Substances 0.000 claims description 2
- 208000037149 Facioscapulohumeral dystrophy Diseases 0.000 claims 2
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 claims 2
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 claims 2
- 206010068871 Myotonic dystrophy Diseases 0.000 claims 2
- 201000009110 Oculopharyngeal muscular dystrophy Diseases 0.000 claims 2
- 201000006815 congenital muscular dystrophy Diseases 0.000 claims 2
- 208000008570 facioscapulohumeral muscular dystrophy Diseases 0.000 claims 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 125000003473 lipid group Chemical group 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 69
- 238000000034 method Methods 0.000 abstract description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
- 210000003205 muscle Anatomy 0.000 abstract description 12
- 210000001519 tissue Anatomy 0.000 abstract description 9
- 210000000988 bone and bone Anatomy 0.000 abstract description 8
- 210000003743 erythrocyte Anatomy 0.000 abstract description 6
- 230000012010 growth Effects 0.000 abstract description 6
- 239000000203 mixture Substances 0.000 abstract description 5
- 210000000845 cartilage Anatomy 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 238000012216 screening Methods 0.000 abstract description 4
- 230000002159 abnormal effect Effects 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 3
- 210000000944 nerve tissue Anatomy 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- 108010057453 activin receptor type II-B Proteins 0.000 description 424
- 238000006467 substitution reaction Methods 0.000 description 177
- 229940024606 amino acid Drugs 0.000 description 163
- 239000012634 fragment Substances 0.000 description 143
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 103
- 230000000875 corresponding effect Effects 0.000 description 101
- 102100027647 Activin receptor type-2B Human genes 0.000 description 97
- 230000004927 fusion Effects 0.000 description 85
- 239000000488 activin Substances 0.000 description 77
- 108010059616 Activins Proteins 0.000 description 75
- 102100026818 Inhibin beta E chain Human genes 0.000 description 74
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 68
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 68
- 239000004472 Lysine Substances 0.000 description 68
- 230000015572 biosynthetic process Effects 0.000 description 65
- 108010029485 Protein Isoforms Proteins 0.000 description 56
- 102000001708 Protein Isoforms Human genes 0.000 description 56
- 230000027455 binding Effects 0.000 description 55
- 101000799193 Homo sapiens Activin receptor type-1C Proteins 0.000 description 54
- 101000799140 Homo sapiens Activin receptor type-1 Proteins 0.000 description 53
- 108091028043 Nucleic acid sequence Proteins 0.000 description 52
- 239000002243 precursor Substances 0.000 description 47
- 230000003993 interaction Effects 0.000 description 46
- 101000712669 Homo sapiens TGF-beta receptor type-2 Proteins 0.000 description 44
- 239000000833 heterodimer Substances 0.000 description 44
- 108010057429 activin receptor type II-A Proteins 0.000 description 43
- 101000799189 Homo sapiens Activin receptor type-1B Proteins 0.000 description 41
- 101000984546 Homo sapiens Bone morphogenetic protein receptor type-1B Proteins 0.000 description 40
- 108010063130 Type II Bone Morphogenetic Protein Receptors Proteins 0.000 description 40
- 101000934638 Homo sapiens Bone morphogenetic protein receptor type-1A Proteins 0.000 description 38
- 230000035772 mutation Effects 0.000 description 37
- 108010076504 Protein Sorting Signals Proteins 0.000 description 36
- 230000000295 complement effect Effects 0.000 description 36
- 102220578642 Chorion-specific transcription factor GCMb_K74M_mutation Human genes 0.000 description 35
- 235000018417 cysteine Nutrition 0.000 description 32
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 32
- 241000282414 Homo sapiens Species 0.000 description 30
- 102000005962 receptors Human genes 0.000 description 30
- 108020003175 receptors Proteins 0.000 description 30
- 125000000539 amino acid group Chemical group 0.000 description 26
- 102100034111 Activin receptor type-1 Human genes 0.000 description 25
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 25
- 102100021886 Activin receptor type-2A Human genes 0.000 description 24
- 102100033455 TGF-beta receptor type-2 Human genes 0.000 description 24
- 102100027052 Bone morphogenetic protein receptor type-1B Human genes 0.000 description 22
- 102100025422 Bone morphogenetic protein receptor type-2 Human genes 0.000 description 22
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 21
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 21
- 102100025423 Bone morphogenetic protein receptor type-1A Human genes 0.000 description 21
- 102100034135 Activin receptor type-1C Human genes 0.000 description 20
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 20
- 230000001965 increasing effect Effects 0.000 description 20
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 description 19
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 18
- 102100034134 Activin receptor type-1B Human genes 0.000 description 18
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 18
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 18
- 235000003704 aspartic acid Nutrition 0.000 description 18
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 18
- 102220638160 Arylamine N-acetyltransferase 1_R64K_mutation Human genes 0.000 description 17
- 102220525561 Coiled-coil domain-containing protein 200_A24N_mutation Human genes 0.000 description 17
- 230000002378 acidificating effect Effects 0.000 description 17
- 230000006698 induction Effects 0.000 description 17
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 16
- -1 109 Chemical compound 0.000 description 15
- 239000004475 Arginine Substances 0.000 description 15
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 15
- 102220567352 Ornithine decarboxylase antizyme 1_K74F_mutation Human genes 0.000 description 15
- 102220633854 PRKCA-binding protein_D80A_mutation Human genes 0.000 description 15
- 102220577876 Poly(rC)-binding protein 1_W78A_mutation Human genes 0.000 description 15
- 102220469872 Protein argonaute-3_E37A_mutation Human genes 0.000 description 15
- 239000004473 Threonine Substances 0.000 description 15
- 102220479829 Voltage-dependent L-type calcium channel subunit beta-2_R56K_mutation Human genes 0.000 description 15
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 15
- 102220004761 rs33990858 Human genes 0.000 description 15
- 102220005147 rs34173382 Human genes 0.000 description 15
- 102220125519 rs562411087 Human genes 0.000 description 15
- 102200089383 rs57977969 Human genes 0.000 description 15
- 102200151008 rs863225226 Human genes 0.000 description 15
- 241000894007 species Species 0.000 description 15
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 14
- 102220610729 Myogenic factor 5_L79P_mutation Human genes 0.000 description 14
- 102220495689 Putative uncharacterized protein FLJ43944_R40A_mutation Human genes 0.000 description 14
- 102220479051 CD59 glycoprotein_L79D_mutation Human genes 0.000 description 13
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 13
- 102000007474 Multiprotein Complexes Human genes 0.000 description 13
- 108010085220 Multiprotein Complexes Proteins 0.000 description 13
- 102220542870 Presenilins-associated rhomboid-like protein, mitochondrial_L79E_mutation Human genes 0.000 description 13
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 13
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 13
- 102220469729 Voltage-dependent L-type calcium channel subunit beta-2_D54K_mutation Human genes 0.000 description 13
- 230000001086 cytosolic effect Effects 0.000 description 13
- 102220100897 rs201542692 Human genes 0.000 description 13
- 102000035160 transmembrane proteins Human genes 0.000 description 13
- 108091005703 transmembrane proteins Proteins 0.000 description 13
- 102220575187 Egl nine homolog 1_F82A_mutation Human genes 0.000 description 12
- 108091006020 Fc-tagged proteins Proteins 0.000 description 12
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 12
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 12
- 102220496976 Platelet-activating factor acetylhydrolase 2, cytoplasmic_L79A_mutation Human genes 0.000 description 12
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 12
- 235000004279 alanine Nutrition 0.000 description 12
- 102100040896 Growth/differentiation factor 15 Human genes 0.000 description 10
- 101000937269 Homo sapiens Activin receptor type-2B Proteins 0.000 description 10
- 101000893549 Homo sapiens Growth/differentiation factor 15 Proteins 0.000 description 10
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 10
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 10
- 239000000306 component Substances 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 102000045412 human ACVR2B Human genes 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 229960000187 tissue plasminogen activator Drugs 0.000 description 10
- 108060003951 Immunoglobulin Proteins 0.000 description 9
- 241000269370 Xenopus <genus> Species 0.000 description 9
- 102000055895 human ACVR1C Human genes 0.000 description 9
- 102000018358 immunoglobulin Human genes 0.000 description 9
- 102100028726 Bone morphogenetic protein 10 Human genes 0.000 description 8
- 101000695367 Homo sapiens Bone morphogenetic protein 10 Proteins 0.000 description 8
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 8
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 8
- 230000004988 N-glycosylation Effects 0.000 description 8
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 8
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 8
- 108010023079 activin B Proteins 0.000 description 8
- 230000004071 biological effect Effects 0.000 description 8
- 150000001720 carbohydrates Chemical group 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000002131 composite material Substances 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 230000002209 hydrophobic effect Effects 0.000 description 8
- 239000004474 valine Substances 0.000 description 8
- 229960004295 valine Drugs 0.000 description 8
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 description 7
- 102100035364 Growth/differentiation factor 3 Human genes 0.000 description 7
- 102100035363 Growth/differentiation factor 7 Human genes 0.000 description 7
- 101000693801 Homo sapiens Anti-Muellerian hormone type-2 receptor Proteins 0.000 description 7
- 101000899390 Homo sapiens Bone morphogenetic protein 6 Proteins 0.000 description 7
- 101001023986 Homo sapiens Growth/differentiation factor 3 Proteins 0.000 description 7
- 101001023968 Homo sapiens Growth/differentiation factor 7 Proteins 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- CJLHTKGWEUGORV-UHFFFAOYSA-N Artemin Chemical compound C1CC2(C)C(O)CCC(=C)C2(O)C2C1C(C)C(=O)O2 CJLHTKGWEUGORV-UHFFFAOYSA-N 0.000 description 6
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 6
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 6
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 6
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 102100035368 Growth/differentiation factor 6 Human genes 0.000 description 6
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 6
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 6
- 101001023964 Homo sapiens Growth/differentiation factor 6 Proteins 0.000 description 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 229960000310 isoleucine Drugs 0.000 description 6
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 231100000350 mutagenesis Toxicity 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- VYXXMAGSIYIYGD-NWAYQTQBSA-N propan-2-yl 2-[[[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-(pyrimidine-4-carbonylamino)phosphoryl]amino]-2-methylpropanoate Chemical compound CC(C)OC(=O)C(C)(C)NP(=O)(CO[C@H](C)Cn1cnc2c(N)ncnc12)NC(=O)c1ccncn1 VYXXMAGSIYIYGD-NWAYQTQBSA-N 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 101000970954 Homo sapiens Activin receptor type-2A Proteins 0.000 description 5
- 101000712674 Homo sapiens TGF-beta receptor type-1 Proteins 0.000 description 5
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 206010028289 Muscle atrophy Diseases 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 102000049307 human ACVR1B Human genes 0.000 description 5
- 102000052842 human TGFBR1 Human genes 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 238000002703 mutagenesis Methods 0.000 description 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 5
- 230000017854 proteolysis Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 210000002027 skeletal muscle Anatomy 0.000 description 5
- 102220556625 Acyl-coenzyme A thioesterase 11_K55A_mutation Human genes 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 4
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 4
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 4
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 4
- 101710194452 Growth/differentiation factor 11 Proteins 0.000 description 4
- 230000004989 O-glycosylation Effects 0.000 description 4
- 102000043168 TGF-beta family Human genes 0.000 description 4
- 108091085018 TGF-beta family Proteins 0.000 description 4
- 125000003368 amide group Chemical group 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 229940028334 follicle stimulating hormone Drugs 0.000 description 4
- 102000054953 human ACVR1 Human genes 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
- 210000003716 mesoderm Anatomy 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 102220058620 rs869025194 Human genes 0.000 description 4
- 230000000087 stabilizing effect Effects 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
- UBWXUGDQUBIEIZ-UHFFFAOYSA-N (13-methyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl) 3-phenylpropanoate Chemical compound CC12CCC(C3CCC(=O)C=C3CC3)C3C1CCC2OC(=O)CCC1=CC=CC=C1 UBWXUGDQUBIEIZ-UHFFFAOYSA-N 0.000 description 3
- 102000005606 Activins Human genes 0.000 description 3
- 102100026376 Artemin Human genes 0.000 description 3
- 101710205806 Artemin Proteins 0.000 description 3
- 102100028727 Bone morphogenetic protein 15 Human genes 0.000 description 3
- 102100024504 Bone morphogenetic protein 3 Human genes 0.000 description 3
- 102100022526 Bone morphogenetic protein 5 Human genes 0.000 description 3
- 101100179813 Drosophila melanogaster Actbeta gene Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000016970 Follistatin Human genes 0.000 description 3
- 108010014612 Follistatin Proteins 0.000 description 3
- 108010070675 Glutathione transferase Proteins 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 102100035379 Growth/differentiation factor 5 Human genes 0.000 description 3
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- 101000695360 Homo sapiens Bone morphogenetic protein 15 Proteins 0.000 description 3
- 101000762375 Homo sapiens Bone morphogenetic protein 3 Proteins 0.000 description 3
- 101000899388 Homo sapiens Bone morphogenetic protein 5 Proteins 0.000 description 3
- 101001023988 Homo sapiens Growth/differentiation factor 5 Proteins 0.000 description 3
- 101000692878 Homo sapiens Regulator of MON1-CCZ1 complex Proteins 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 3
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 3
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 3
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 3
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 3
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 3
- 210000000577 adipose tissue Anatomy 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000022159 cartilage development Effects 0.000 description 3
- 230000022811 deglycosylation Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000013020 embryo development Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000037257 muscle growth Effects 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000022379 skeletal muscle tissue development Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010006895 Cachexia Diseases 0.000 description 2
- 102220578645 Chorion-specific transcription factor GCMb_N65A_mutation Human genes 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- 102100029379 Follistatin-related protein 3 Human genes 0.000 description 2
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101001062529 Homo sapiens Follistatin-related protein 3 Proteins 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 2
- 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000029578 Muscle disease Diseases 0.000 description 2
- 108010056852 Myostatin Proteins 0.000 description 2
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 102100021584 Neurturin Human genes 0.000 description 2
- 108010015406 Neurturin Proteins 0.000 description 2
- 102000044547 Nodal Human genes 0.000 description 2
- 108700024442 Nodal Proteins 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102220558380 Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16_F82K_mutation Human genes 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 102000007374 Smad Proteins Human genes 0.000 description 2
- 108010007945 Smad Proteins Proteins 0.000 description 2
- 108010051765 Type I Bone Morphogenetic Protein Receptors Proteins 0.000 description 2
- 102000000523 Type II Activin Receptors Human genes 0.000 description 2
- 108010041546 Type II Activin Receptors Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 230000003466 anti-cipated effect Effects 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000000254 damaging effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- 230000007783 downstream signaling Effects 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 150000002338 glycosides Chemical class 0.000 description 2
- 239000000185 hemagglutinin Substances 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000000893 inhibin Substances 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 150000002632 lipids Chemical group 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 238000002887 multiple sequence alignment Methods 0.000 description 2
- 230000020763 muscle atrophy Effects 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 230000004766 neurogenesis Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 210000000963 osteoblast Anatomy 0.000 description 2
- 230000002188 osteogenic effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 238000000059 patterning Methods 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000009290 primary effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 102220157866 rs147372618 Human genes 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000011100 viral filtration Methods 0.000 description 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 208000037415 AIDS wasting syndrome Diseases 0.000 description 1
- 102000018918 Activin Receptors Human genes 0.000 description 1
- 108010052946 Activin Receptors Proteins 0.000 description 1
- 101710173011 Activin receptor type-1B Proteins 0.000 description 1
- 101710173005 Activin receptor type-1C Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- 244000186140 Asperula odorata Species 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 102100028728 Bone morphogenetic protein 1 Human genes 0.000 description 1
- 108090000654 Bone morphogenetic protein 1 Proteins 0.000 description 1
- 101000937267 Bos taurus Activin receptor type-2B Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000202252 Cerberus Species 0.000 description 1
- 102220601920 Cerebral dopamine neurotrophic factor_S169N_mutation Human genes 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102100037241 Endoglin Human genes 0.000 description 1
- 108010036395 Endoglin Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010074864 Factor XI Proteins 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 102220568165 Fatty acid-binding protein, adipocyte_P76L_mutation Human genes 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 101150050927 Fcgrt gene Proteins 0.000 description 1
- 108010012820 Follistatin-Related Proteins Proteins 0.000 description 1
- 102000019203 Follistatin-Related Proteins Human genes 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 208000036119 Frailty Diseases 0.000 description 1
- 235000008526 Galium odoratum Nutrition 0.000 description 1
- KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000003577 HIV wasting syndrome Diseases 0.000 description 1
- 101000961145 Homo sapiens Immunoglobulin heavy constant gamma 3 Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102100039348 Immunoglobulin heavy constant gamma 3 Human genes 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 206010024305 Leukaemia monocytic Diseases 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 208000029725 Metabolic bone disease Diseases 0.000 description 1
- 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 1
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100369076 Mus musculus Tdgf1 gene Proteins 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100037224 Noncompact myelin-associated protein Human genes 0.000 description 1
- 101710184695 Noncompact myelin-associated protein Proteins 0.000 description 1
- 208000011623 Obstructive Lung disease Diseases 0.000 description 1
- 239000004235 Orange GGN Substances 0.000 description 1
- 206010049088 Osteopenia Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010030544 Peptidyl-Lys metalloendopeptidase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100490435 Rattus norvegicus Acvr1c gene Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000005770 Secondary Hyperparathyroidism Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 102100033456 TGF-beta receptor type-1 Human genes 0.000 description 1
- 102000002933 Thioredoxin Human genes 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000026062 Tissue disease Diseases 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 108010011702 Transforming Growth Factor-beta Type I Receptor Proteins 0.000 description 1
- 102000019044 Type I Bone Morphogenetic Protein Receptors Human genes 0.000 description 1
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000011759 adipose tissue development Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 102220370152 c.131G>C Human genes 0.000 description 1
- 102220384347 c.298A>G Human genes 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004422 calculation algorithm Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 230000009786 epithelial differentiation Effects 0.000 description 1
- 230000010437 erythropoiesis Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 208000020694 gallbladder disease Diseases 0.000 description 1
- 101150004578 gdf-8 gene Proteins 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 201000003617 glucocorticoid-induced osteoporosis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000017687 left/right axis specification Effects 0.000 description 1
- 150000002614 leucines Chemical class 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 210000000982 limb bud Anatomy 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000004777 loss-of-function mutation Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 201000006894 monocytic leukemia Diseases 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 238000012433 multimodal chromatography Methods 0.000 description 1
- 230000009753 muscle formation Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 208000013315 neuromuscular junction disease Diseases 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 208000030212 nutrition disease Diseases 0.000 description 1
- 210000001706 olfactory mucosa Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000007261 regionalization Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 102220220520 rs1060503090 Human genes 0.000 description 1
- 102220278863 rs1395998044 Human genes 0.000 description 1
- 102220125997 rs141863326 Human genes 0.000 description 1
- 102220288227 rs141863326 Human genes 0.000 description 1
- 102220039284 rs199473359 Human genes 0.000 description 1
- 102220036189 rs273585616 Human genes 0.000 description 1
- 102220058274 rs45617634 Human genes 0.000 description 1
- 102200108223 rs869312782 Human genes 0.000 description 1
- 208000001076 sarcopenia Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Epidemiology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662404718P | 2016-10-05 | 2016-10-05 | |
| US62/404,718 | 2016-10-05 | ||
| KR1020197012902A KR102595559B1 (ko) | 2016-10-05 | 2017-10-05 | 변이체 actriib 단백질 및 이의 용도 |
| PCT/US2017/055421 WO2018067874A1 (en) | 2016-10-05 | 2017-10-05 | Variant actriib proteins and uses thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197012902A Division KR102595559B1 (ko) | 2016-10-05 | 2017-10-05 | 변이체 actriib 단백질 및 이의 용도 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20230152811A KR20230152811A (ko) | 2023-11-03 |
| KR102761094B1 true KR102761094B1 (ko) | 2025-02-03 |
Family
ID=61831930
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020237036672A Active KR102761094B1 (ko) | 2016-10-05 | 2017-10-05 | 변이체 actriib 단백질 및 이의 용도 |
| KR1020197012902A Active KR102595559B1 (ko) | 2016-10-05 | 2017-10-05 | 변이체 actriib 단백질 및 이의 용도 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197012902A Active KR102595559B1 (ko) | 2016-10-05 | 2017-10-05 | 변이체 actriib 단백질 및 이의 용도 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US11267865B2 (enExample) |
| EP (1) | EP3523328A4 (enExample) |
| JP (2) | JP7280182B2 (enExample) |
| KR (2) | KR102761094B1 (enExample) |
| CN (1) | CN110036025B (enExample) |
| AU (3) | AU2017338916B2 (enExample) |
| BR (1) | BR112019006918A2 (enExample) |
| CA (1) | CA3039525A1 (enExample) |
| MA (1) | MA46471A (enExample) |
| WO (1) | WO2018067874A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| JP2018501307A (ja) | 2014-12-03 | 2018-01-18 | セルジーン コーポレイション | アクチビン−ＡｃｔＲＩＩアンタゴニスト及び貧血を治療するための使用 |
| PT3286206T (pt) | 2015-04-22 | 2021-04-01 | Biogen Ma Inc | Novas proteínas híbridas bloqueadoras de ligando actriib para tratar doenças de desgaste muscular |
| WO2017177013A1 (en) | 2016-04-06 | 2017-10-12 | Acceleron Pharma Inc. | Alk7 antagonists and uses thereof |
| EP3523328A4 (en) | 2016-10-05 | 2020-04-01 | Acceleron Pharma Inc. | VARIANT ACTRIIB PROTEINS AND USES THEREOF |
| JOP20190085A1 (ar) * | 2016-10-20 | 2019-04-17 | Biogen Ma Inc | طرق علاج الضمور العضلي ومرض العظام باستخدام بروتينات احتجاز مركب ترابطي actriib هجين حديثة |
| WO2018089706A2 (en) | 2016-11-10 | 2018-05-17 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| WO2019094751A1 (en) | 2017-11-09 | 2019-05-16 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| KR20200109330A (ko) | 2018-01-12 | 2020-09-22 | 케로스 테라퓨틱스, 인크. | 액티빈 수용체 유형 iib 변이체 및 그의 사용 방법 |
| CA3099527A1 (en) | 2018-05-03 | 2019-11-07 | Acceleron Pharma Inc. | Multispecific binders of tgf.beta.-superfamily ligands and uses thereof |
| US12168683B2 (en) | 2018-05-03 | 2024-12-17 | Acceleron Pharma Inc. | Binders of TGFβ-superfamily ligands and uses thereof |
| AU2019266314B2 (en) * | 2018-05-09 | 2025-05-15 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| AU2019285299A1 (en) * | 2018-06-15 | 2020-12-03 | Acceleron Pharma Inc. | Bi-and tri-functional fusion proteins and uses thereof |
| CN109293763B (zh) * | 2018-10-26 | 2021-10-26 | 中国农业科学院特产研究所 | 水貂激活素b蛋白及其制备与应用 |
| CN114761013A (zh) | 2019-09-27 | 2022-07-15 | 迪斯克医药公司 | 治疗骨髓纤维化和相关病症的方法 |
| BR112022015387A2 (pt) * | 2020-02-03 | 2022-10-11 | Acceleron Pharma Inc | Proteínas actriib variantes e usos das mesmas |
| WO2021189010A1 (en) * | 2020-03-20 | 2021-09-23 | Keros Therapeutics, Inc. | Methods of using activin receptor type iib variants |
| WO2021189006A1 (en) * | 2020-03-20 | 2021-09-23 | Keros Therapeutics, Inc. | Methods of using activin receptor type iia variants |
| KR20230012539A (ko) | 2020-05-13 | 2023-01-26 | 디스크 메디슨, 인크. | 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체 |
| WO2021263128A1 (en) * | 2020-06-25 | 2021-12-30 | Gliknik Inc. | Ace2-fc fusion proteins and methods of use |
| US12186370B1 (en) | 2020-11-05 | 2025-01-07 | Celgene Corporation | ACTRIIB ligand trap compositions and uses thereof |
| EP4274600A4 (en) * | 2021-01-08 | 2024-11-20 | Acceleron Pharma Inc. | COMPOSITIONS AND METHODS FOR THE TREATMENT OF PULMONARY HYPERTENSION |
| KR20240150761A (ko) | 2022-01-28 | 2024-10-16 | 35파마 인크. | 액티빈 수용체 유형 iib 변이체 및 이의 용도 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100016558A1 (en) | 1991-05-10 | 2010-01-21 | The Salk Institute For Biological Studies | Cloning and recombinant production of receptor(s) of the activin/tgf-beta superfamily |
| US20100286374A1 (en) | 2008-01-07 | 2010-11-11 | Gunasekaran Kannan | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
| KR101669278B1 (ko) | 2007-02-02 | 2016-10-25 | 악셀레론 파마 인코포레이티드 | ＡｃｔＲⅡＢ로부터 유도된 변이체 및 이의 용도 |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0105014B1 (en) | 1982-09-24 | 1992-05-20 | THE UNITED STATES OF AMERICA as represented by the Secretary United States Department of Commerce | Repair of tissue in animals |
| NZ210699A (en) | 1984-01-04 | 1989-06-28 | Int Genetic Eng | Isolation of an osteogenic protein of the p3 immunologically related family |
| DE3588058T3 (de) | 1984-07-16 | 2005-04-07 | Celtrix Pharmaceuticals, Inc., Palo Alto | Knorpel-induzierende Polypeptid-Faktoren aus Knochen |
| WO1987005330A1 (en) | 1986-03-07 | 1987-09-11 | Michel Louis Eugene Bergh | Method for enhancing glycoprotein stability |
| US5080891A (en) | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| US5932448A (en) | 1991-11-29 | 1999-08-03 | Protein Design Labs., Inc. | Bispecific antibody heterodimers |
| US5677196A (en) | 1993-05-18 | 1997-10-14 | University Of Utah Research Foundation | Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays |
| US5525490A (en) | 1994-03-29 | 1996-06-11 | Onyx Pharmaceuticals, Inc. | Reverse two-hybrid method |
| US5814565A (en) | 1995-02-23 | 1998-09-29 | University Of Utah Research Foundation | Integrated optic waveguide immunosensor |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| NZ306767A (en) | 1995-04-11 | 2000-03-27 | Univ Johns Hopkins | Method of identifying molecular interactions employing counterselection and at least two hybrid molecules or two hybrid systems |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| WO1999006563A1 (en) | 1997-07-30 | 1999-02-11 | Emory University | Novel bone mineralization proteins, dna, vectors, expression systems |
| ATE322681T1 (de) | 1999-01-21 | 2006-04-15 | Metamorphix Inc | Inhibitoren für wachstumdifferenzierungsfaktor und ihre anwendungen |
| US7456149B2 (en) | 2004-03-02 | 2008-11-25 | Acceleron Pharma, Inc. | ALK7 and myostatin inhibitors and uses thereof |
| ES2426005T3 (es) | 2004-07-23 | 2013-10-18 | Acceleron Pharma Inc. | Polipéptidos del receptor ACTRII, procedimientos y composiciones |
| US20090182127A1 (en) | 2006-06-22 | 2009-07-16 | Novo Nordisk A/S | Production of Bispecific Antibodies |
| UA116871C2 (uk) | 2006-12-18 | 2018-05-25 | Акселерон Фарма Інк. | СПОСІБ ЛІКУВАННЯ МІЄЛОДИСПЛАСТИЧНОГО СИНДРОМУ, ТАЛАСЕМІЇ ТА СЕРПОПОДІБНО-КЛІТИННОЇ АНЕМІЇ ЗА ДОПОМОГОЮ ЗАСТОСУВАННЯ АНТАГОНІСТА АКТИВІНУ ПОЛІПЕПТИДУ ActRII |
| US20100028332A1 (en) | 2006-12-18 | 2010-02-04 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| KR20110031908A (ko) | 2008-05-02 | 2011-03-29 | 악셀레론 파마 인코포레이티드 | 혈관신생 및 혈관주위세포 적용범위의 조정을 위한 ａｌｋ１ 길항제 기재의 방법 및 조성물 |
| EP2318028B1 (en) | 2008-06-26 | 2020-02-19 | Acceleron Pharma Inc. | Antagonists of soluble activin-actriia and uses for increasing red blood cell levels |
| US8216997B2 (en) | 2008-08-14 | 2012-07-10 | Acceleron Pharma, Inc. | Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators |
| HUE051137T2 (hu) | 2008-08-14 | 2021-03-01 | Acceleron Pharma Inc | GDF-csapdák |
| WO2010083034A1 (en) | 2009-01-13 | 2010-07-22 | Acceleron Pharma Inc. | Methods for increasing adiponectin |
| KR101805201B1 (ko) | 2009-03-30 | 2017-12-05 | 악셀레론 파마 인코포레이티드 | Ｂｍｐ-ａｌｋ3 길항제 및 골 성장을 촉진시키는 사용되는 이의 용도 |
| EP2440577A4 (en) * | 2009-06-12 | 2013-01-23 | Acceleron Pharma Inc | SHORTEN ACTRIIB FC FUSION PROTEINS |
| ES2844123T3 (es) * | 2009-08-13 | 2021-07-21 | Acceleron Pharma Inc | Uso combinado de trampas de GDF y activadores del receptor de la eritropoyetina para aumentar los niveles de glóbulos rojos |
| MX340451B (es) * | 2009-09-09 | 2016-07-08 | Acceleron Pharma Inc | Antagonistas de actriib y dosificacion y usos de los mismos. |
| JP6091894B2 (ja) | 2009-09-16 | 2017-03-15 | ジェネンテック， インコーポレイテッド | コイルドコイルおよび／またはテザー含有タンパク質複合体およびその使用 |
| WO2012027065A2 (en) | 2010-08-27 | 2012-03-01 | Celgene Corporation | Combination therapy for treatment of disease |
| CN102850458B (zh) | 2011-06-28 | 2014-10-01 | 华博生物医药技术（上海）有限公司 | 新型重组双功能融合蛋白及其制法和用途 |
| CN107837390A (zh) | 2011-10-17 | 2018-03-27 | 阿塞勒隆制药公司 | 用于治疗无效性红细胞生成的方法和组合物 |
| WO2013063536A1 (en) | 2011-10-27 | 2013-05-02 | Acceleron Pharma, Inc. | Actriib binding agents and uses thereof |
| HK1225740A1 (zh) | 2013-08-22 | 2017-09-15 | Acceleron Pharma Inc. | TGF-β受体II型变体及其用途 |
| KR102520970B1 (ko) * | 2014-03-21 | 2023-04-12 | 악셀레론 파마 인코포레이티드 | 액티빈 b 및/또는 gdf11을 억제함으로써 적혈 혈액 세포 수준을 증가시키고 비효율적인 적혈구 생성을 치료하는 방법 |
| EP3808778A1 (en) * | 2014-04-18 | 2021-04-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating sickle-cell disease |
| CN107135646B (zh) * | 2014-06-13 | 2022-03-15 | 阿塞勒隆制药公司 | 用于治疗溃疡的方法和组合物 |
| JP2018501307A (ja) | 2014-12-03 | 2018-01-18 | セルジーン コーポレイション | アクチビン−ＡｃｔＲＩＩアンタゴニスト及び貧血を治療するための使用 |
| MA53400A (fr) | 2015-04-06 | 2021-08-04 | Acceleron Pharma Inc | Hétéromultimères alk7: actriib et leurs utilisations |
| CN113683708A (zh) | 2015-04-06 | 2021-11-23 | 阿塞勒隆制药公司 | 单臂i型和ii型受体融合蛋白和其用途 |
| MA41919A (fr) | 2015-04-06 | 2018-02-13 | Acceleron Pharma Inc | Hétéromultimères alk4:actriib et leurs utilisations |
| PT3286206T (pt) | 2015-04-22 | 2021-04-01 | Biogen Ma Inc | Novas proteínas híbridas bloqueadoras de ligando actriib para tratar doenças de desgaste muscular |
| WO2016205370A1 (en) | 2015-06-15 | 2016-12-22 | Santa Maria Biotherapeutics, Inc. | Methods of using activin receptor iib-based proteins |
| EP3344660B1 (en) | 2015-08-31 | 2025-03-05 | National Research Council of Canada | Tgf-beta-receptor ectodomain fusion molecules and uses thereof |
| WO2017177013A1 (en) | 2016-04-06 | 2017-10-12 | Acceleron Pharma Inc. | Alk7 antagonists and uses thereof |
| CA3029890A1 (en) | 2016-07-07 | 2018-01-11 | Acceleron Pharma Inc. | Tgf-beta superfamily heteromultimers and uses thereof |
| EP3523328A4 (en) | 2016-10-05 | 2020-04-01 | Acceleron Pharma Inc. | VARIANT ACTRIIB PROTEINS AND USES THEREOF |
| AU2017338921A1 (en) | 2016-10-05 | 2019-04-18 | Acceleron Pharma Inc. | ALK4:ActRIIB heteromultimers and uses thereof |
| JP7097354B2 (ja) | 2016-10-05 | 2022-07-07 | アクセルロン ファーマ インコーポレイテッド | Ｔｇｆ－ベータスーパーファミリーｉ型およびｉｉ型受容体ヘテロ多量体ならびにその使用 |
| JOP20190085A1 (ar) | 2016-10-20 | 2019-04-17 | Biogen Ma Inc | طرق علاج الضمور العضلي ومرض العظام باستخدام بروتينات احتجاز مركب ترابطي actriib هجين حديثة |
| WO2018089706A2 (en) | 2016-11-10 | 2018-05-17 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
-
2017
- 2017-10-05 EP EP17859219.2A patent/EP3523328A4/en active Pending
- 2017-10-05 JP JP2019518302A patent/JP7280182B2/ja active Active
- 2017-10-05 CA CA3039525A patent/CA3039525A1/en active Pending
- 2017-10-05 MA MA046471A patent/MA46471A/fr unknown
- 2017-10-05 KR KR1020237036672A patent/KR102761094B1/ko active Active
- 2017-10-05 BR BR112019006918A patent/BR112019006918A2/pt unknown
- 2017-10-05 AU AU2017338916A patent/AU2017338916B2/en active Active
- 2017-10-05 US US16/340,048 patent/US11267865B2/en active Active
- 2017-10-05 WO PCT/US2017/055421 patent/WO2018067874A1/en not_active Ceased
- 2017-10-05 CN CN201780074935.6A patent/CN110036025B/zh active Active
- 2017-10-05 KR KR1020197012902A patent/KR102595559B1/ko active Active
-
2022
- 2022-03-07 US US17/687,934 patent/US12240887B2/en active Active
- 2022-03-11 AU AU2022201698A patent/AU2022201698A1/en not_active Abandoned
-
2023
- 2023-01-19 JP JP2023006458A patent/JP7617962B2/ja active Active
-
2024
- 2024-02-05 AU AU2024200684A patent/AU2024200684A1/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100016558A1 (en) | 1991-05-10 | 2010-01-21 | The Salk Institute For Biological Studies | Cloning and recombinant production of receptor(s) of the activin/tgf-beta superfamily |
| KR101669278B1 (ko) | 2007-02-02 | 2016-10-25 | 악셀레론 파마 인코포레이티드 | ＡｃｔＲⅡＢ로부터 유도된 변이체 및 이의 용도 |
| KR101801506B1 (ko) | 2007-02-02 | 2017-11-24 | 악셀레론 파마 인코포레이티드 | ＡｃｔＲⅡＢ로부터 유도된 변이체 및 이의 용도 |
| KR102072897B1 (ko) | 2007-02-02 | 2020-02-03 | 악셀레론 파마 인코포레이티드 | ＡｃｔＲⅡＢ로부터 유도된 변이체 및 이의 용도 |
| KR102317987B1 (ko) | 2007-02-02 | 2021-10-28 | 악셀레론 파마 인코포레이티드 | ＡｃｔＲⅡＢ로부터 유도된 변이체 및 이의 용도 |
| KR102382781B1 (ko) | 2007-02-02 | 2022-04-04 | 악셀레론 파마 인코포레이티드 | ＡｃｔＲⅡＢ로부터 유도된 변이체 및 이의 용도 |
| US20100286374A1 (en) | 2008-01-07 | 2010-11-11 | Gunasekaran Kannan | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3523328A1 (en) | 2019-08-14 |
| WO2018067874A1 (en) | 2018-04-12 |
| US20200055919A1 (en) | 2020-02-20 |
| AU2022201698A1 (en) | 2022-04-07 |
| JP2023033573A (ja) | 2023-03-10 |
| KR102595559B1 (ko) | 2023-10-30 |
| JP7617962B2 (ja) | 2025-01-20 |
| AU2017338916A1 (en) | 2019-04-18 |
| KR20230152811A (ko) | 2023-11-03 |
| AU2024200684A1 (en) | 2024-02-22 |
| KR20190073414A (ko) | 2019-06-26 |
| CA3039525A1 (en) | 2018-04-12 |
| BR112019006918A2 (pt) | 2019-06-25 |
| MA46471A (fr) | 2021-05-19 |
| AU2017338916B2 (en) | 2022-03-24 |
| US20220306724A1 (en) | 2022-09-29 |
| CN110036025A (zh) | 2019-07-19 |
| JP2019536440A (ja) | 2019-12-19 |
| JP7280182B2 (ja) | 2023-05-23 |
| US12240887B2 (en) | 2025-03-04 |
| US11267865B2 (en) | 2022-03-08 |
| CN110036025B (zh) | 2024-03-22 |
| EP3523328A4 (en) | 2020-04-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12240887B2 (en) | Variant ActRIIB proteins and uses thereof | |
| US12338273B2 (en) | Single-arm type I and type II receptor fusion proteins and uses thereof | |
| US20240158468A1 (en) | Tgf-beta superfamily type i and type ii receptor heteromultimers and uses thereof | |
| US12421295B2 (en) | TGF-beta superfamily type I and type II receptor heteromultimers and uses thereof | |
| HK40064908A (en) | Single-arm type i and type ii receptor fusion proteins and uses thereof | |
| HK40061777A (en) | Single-arm type i and type ii receptor fusion proteins and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A107 | Divisional application of patent | ||
| PA0104 | Divisional application for international application |
Comment text: Divisional Application for International Patent Patent event code: PA01041R01D Patent event date: 20231025 Application number text: 1020197012902 Filing date: 20190503 |
|
| PG1501 | Laying open of application | ||
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20241015 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20250111 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20250123 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20250123 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration |