TW202130652A - Apoc-ii擬肽 - Google Patents
Apoc-ii擬肽 Download PDFInfo
- Publication number
- TW202130652A TW202130652A TW109138699A TW109138699A TW202130652A TW 202130652 A TW202130652 A TW 202130652A TW 109138699 A TW109138699 A TW 109138699A TW 109138699 A TW109138699 A TW 109138699A TW 202130652 A TW202130652 A TW 202130652A
- Authority
- TW
- Taiwan
- Prior art keywords
- peptide
- apoc
- helix
- amino acid
- fatty acid
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 426
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 68
- 208000006575 hypertriglyceridemia Diseases 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 52
- 102100039998 Apolipoprotein C-II Human genes 0.000 claims abstract description 19
- 108010024284 Apolipoprotein C-II Proteins 0.000 claims abstract description 18
- 235000001014 amino acid Nutrition 0.000 claims description 372
- 150000001413 amino acids Chemical class 0.000 claims description 281
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 205
- 229930195729 fatty acid Natural products 0.000 claims description 205
- 239000000194 fatty acid Substances 0.000 claims description 205
- 150000004665 fatty acids Chemical class 0.000 claims description 205
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 181
- 239000000816 peptidomimetic Substances 0.000 claims description 162
- 108010013563 Lipoprotein Lipase Proteins 0.000 claims description 113
- 102000043296 Lipoprotein lipases Human genes 0.000 claims description 107
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 107
- 238000006467 substitution reaction Methods 0.000 claims description 100
- 210000002966 serum Anatomy 0.000 claims description 89
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 72
- 239000004472 Lysine Substances 0.000 claims description 71
- 230000035772 mutation Effects 0.000 claims description 70
- 238000007385 chemical modification Methods 0.000 claims description 61
- 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 claims description 55
- 102000004895 Lipoproteins Human genes 0.000 claims description 42
- 108090001030 Lipoproteins Proteins 0.000 claims description 42
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 39
- 125000000539 amino acid group Chemical group 0.000 claims description 39
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 38
- 235000003704 aspartic acid Nutrition 0.000 claims description 37
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 37
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 36
- 230000000694 effects Effects 0.000 claims description 34
- 230000004130 lipolysis Effects 0.000 claims description 30
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 29
- 235000004279 alanine Nutrition 0.000 claims description 28
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Chemical group OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 28
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Chemical group OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 27
- 239000004475 Arginine Chemical group 0.000 claims description 26
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 26
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 25
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 25
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 25
- 235000013922 glutamic acid Nutrition 0.000 claims description 25
- 239000004220 glutamic acid Substances 0.000 claims description 25
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 25
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 24
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 24
- 238000001727 in vivo Methods 0.000 claims description 23
- 101000959921 Homo sapiens Apolipoprotein C-II Proteins 0.000 claims description 20
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 20
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical group CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 claims description 19
- 238000012217 deletion Methods 0.000 claims description 19
- 230000037430 deletion Effects 0.000 claims description 19
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 18
- 230000027455 binding Effects 0.000 claims description 17
- 201000011110 familial lipoprotein lipase deficiency Diseases 0.000 claims description 17
- 229930182817 methionine Natural products 0.000 claims description 17
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 15
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 14
- 239000004473 Threonine Substances 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 238000002203 pretreatment Methods 0.000 claims description 13
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 12
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 11
- 239000004471 Glycine Substances 0.000 claims description 11
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 11
- 230000007812 deficiency Effects 0.000 claims description 11
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 11
- 238000000746 purification Methods 0.000 claims description 11
- 238000003786 synthesis reaction Methods 0.000 claims description 11
- 239000004474 valine Substances 0.000 claims description 11
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 10
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 9
- 230000003213 activating effect Effects 0.000 claims description 9
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 9
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 8
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 8
- 238000010254 subcutaneous injection Methods 0.000 claims description 8
- 239000007929 subcutaneous injection Substances 0.000 claims description 8
- 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 claims description 8
- 206010033645 Pancreatitis Diseases 0.000 claims description 7
- 235000012054 meals Nutrition 0.000 claims description 7
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 7
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 6
- 206010033647 Pancreatitis acute Diseases 0.000 claims description 6
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Chemical group C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 6
- 201000003229 acute pancreatitis Diseases 0.000 claims description 6
- 238000011144 upstream manufacturing Methods 0.000 claims description 6
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 claims description 5
- 229920002704 polyhistidine Polymers 0.000 claims description 5
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims description 5
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 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 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 208000001021 Hyperlipoproteinemia Type I Diseases 0.000 claims description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 3
- 238000012300 Sequence Analysis Methods 0.000 claims description 3
- 230000007547 defect Effects 0.000 claims description 3
- 101150062900 lpl gene Proteins 0.000 claims description 3
- 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 claims description 3
- 206010064571 Gene mutation Diseases 0.000 claims description 2
- 238000002651 drug therapy Methods 0.000 claims description 2
- 229940024606 amino acid Drugs 0.000 description 251
- 108090000623 proteins and genes Proteins 0.000 description 58
- 235000018102 proteins Nutrition 0.000 description 57
- 102000004169 proteins and genes Human genes 0.000 description 57
- 238000002347 injection Methods 0.000 description 49
- 239000007924 injection Substances 0.000 description 49
- 241000699670 Mus sp. Species 0.000 description 48
- 239000007928 intraperitoneal injection Substances 0.000 description 35
- 238000000338 in vitro Methods 0.000 description 32
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 32
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 32
- 125000000217 alkyl group Chemical group 0.000 description 31
- 239000000758 substrate Substances 0.000 description 30
- 238000004458 analytical method Methods 0.000 description 29
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 28
- 230000008859 change Effects 0.000 description 28
- 229940028435 intralipid Drugs 0.000 description 26
- 230000004048 modification Effects 0.000 description 25
- 238000012986 modification Methods 0.000 description 25
- 108010027070 Apolipoproteins C Proteins 0.000 description 23
- 102000018655 Apolipoproteins C Human genes 0.000 description 23
- 230000001965 increasing effect Effects 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 150000002632 lipids Chemical class 0.000 description 22
- 239000011780 sodium chloride Substances 0.000 description 22
- 230000007062 hydrolysis Effects 0.000 description 19
- 238000006460 hydrolysis reaction Methods 0.000 description 19
- 230000037396 body weight Effects 0.000 description 18
- 235000021355 Stearic acid Nutrition 0.000 description 17
- 230000002950 deficient Effects 0.000 description 17
- -1 etc.) Proteins 0.000 description 17
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 17
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 17
- 239000008117 stearic acid Substances 0.000 description 17
- 238000011830 transgenic mouse model Methods 0.000 description 17
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 16
- 241000699660 Mus musculus Species 0.000 description 15
- 238000011813 knockout mouse model Methods 0.000 description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 14
- 229920001184 polypeptide Polymers 0.000 description 14
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 13
- 150000001408 amides Chemical group 0.000 description 13
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 241000282693 Cercopithecidae Species 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 12
- 235000018417 cysteine Nutrition 0.000 description 12
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 12
- 238000003209 gene knockout Methods 0.000 description 12
- 230000002209 hydrophobic effect Effects 0.000 description 12
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 12
- 108010010234 HDL Lipoproteins Proteins 0.000 description 11
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 11
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 150000003626 triacylglycerols Chemical class 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 230000000291 postprandial effect Effects 0.000 description 9
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 108010004103 Chylomicrons Proteins 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- 125000002541 furyl group Chemical group 0.000 description 8
- 125000000623 heterocyclic group Chemical group 0.000 description 8
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- DRCWOKJLSQUJPZ-DZGCQCFKSA-N (4ar,9as)-n-ethyl-1,4,9,9a-tetrahydrofluoren-4a-amine Chemical compound C1C2=CC=CC=C2[C@]2(NCC)[C@H]1CC=CC2 DRCWOKJLSQUJPZ-DZGCQCFKSA-N 0.000 description 7
- 108010056301 Apolipoprotein C-III Proteins 0.000 description 7
- 102000030169 Apolipoprotein C-III Human genes 0.000 description 7
- 101001008429 Homo sapiens Nucleobindin-2 Proteins 0.000 description 7
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 7
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 7
- 102100027441 Nucleobindin-2 Human genes 0.000 description 7
- 235000021314 Palmitic acid Nutrition 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 231100000673 dose–response relationship Toxicity 0.000 description 7
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 7
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 7
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 6
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 6
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 6
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 6
- 239000005642 Oleic acid Substances 0.000 description 6
- 235000009582 asparagine Nutrition 0.000 description 6
- 229960001230 asparagine Drugs 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 125000001165 hydrophobic group Chemical group 0.000 description 6
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 6
- 230000029226 lipidation Effects 0.000 description 6
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 231100000240 steatosis hepatitis Toxicity 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 5
- 238000007126 N-alkylation reaction Methods 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 230000010933 acylation Effects 0.000 description 5
- 238000005917 acylation reaction Methods 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 238000011260 co-administration Methods 0.000 description 5
- 238000005520 cutting process Methods 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- RCFKEIREOSXLET-UHFFFAOYSA-N disulfamide Chemical compound CC1=CC(Cl)=C(S(N)(=O)=O)C=C1S(N)(=O)=O RCFKEIREOSXLET-UHFFFAOYSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 235000021588 free fatty acids Nutrition 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 150000002430 hydrocarbons Chemical class 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000003305 oral gavage Methods 0.000 description 5
- 238000010647 peptide synthesis reaction Methods 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 4
- 235000021319 Palmitoleic acid Nutrition 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 238000000516 activation analysis Methods 0.000 description 4
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 4
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 4
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 4
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 4
- 229940090949 docosahexaenoic acid Drugs 0.000 description 4
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 4
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 4
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000013595 glycosylation Effects 0.000 description 4
- 238000006206 glycosylation reaction Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 125000002632 imidazolidinyl group Chemical group 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 125000001786 isothiazolyl group Chemical group 0.000 description 4
- 125000000842 isoxazolyl group Chemical group 0.000 description 4
- 235000020778 linoleic acid Nutrition 0.000 description 4
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 4
- 229960004488 linolenic acid Drugs 0.000 description 4
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 229920001451 polypropylene glycol Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 125000003373 pyrazinyl group Chemical group 0.000 description 4
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 4
- 125000002755 pyrazolinyl group Chemical group 0.000 description 4
- 125000003226 pyrazolyl group Chemical group 0.000 description 4
- 125000002098 pyridazinyl group Chemical group 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 125000001422 pyrrolinyl group Chemical group 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 4
- 125000005505 thiomorpholino group Chemical group 0.000 description 4
- 125000001425 triazolyl group Chemical group 0.000 description 4
- 235000015112 vegetable and seed oil Nutrition 0.000 description 4
- 239000008158 vegetable oil Substances 0.000 description 4
- OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 3
- 241000701489 Cauliflower mosaic virus Species 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 3
- 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 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- 102000007330 LDL Lipoproteins Human genes 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 101710176384 Peptide 1 Proteins 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 241000723873 Tobacco mosaic virus Species 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- GBFLZEXEOZUWRN-UHFFFAOYSA-N carbocisteine Chemical compound OC(=O)C(N)CSCC(O)=O GBFLZEXEOZUWRN-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- 238000003304 gavage Methods 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 210000002706 plastid Anatomy 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 108010005636 polypeptide C Proteins 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 230000007863 steatosis Effects 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000011191 terminal modification Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229920001664 tyloxapol Polymers 0.000 description 3
- 229960004224 tyloxapol Drugs 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- OYIFNHCXNCRBQI-UHFFFAOYSA-N 2-aminoadipic acid Chemical compound OC(=O)C(N)CCCC(O)=O OYIFNHCXNCRBQI-UHFFFAOYSA-N 0.000 description 2
- RDFMDVXONNIGBC-UHFFFAOYSA-N 2-aminoheptanoic acid Chemical compound CCCCCC(N)C(O)=O RDFMDVXONNIGBC-UHFFFAOYSA-N 0.000 description 2
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
- 101150037123 APOE gene Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000793223 Homo sapiens Apolipoprotein C-III Proteins 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 description 2
- YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 description 2
- 108010065338 N-ethylglycine Proteins 0.000 description 2
- KSPIYJQBLVDRRI-UHFFFAOYSA-N N-methylisoleucine Chemical compound CCC(C)C(NC)C(O)=O KSPIYJQBLVDRRI-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 102220537828 Nebulette_S15E_mutation Human genes 0.000 description 2
- 101800005149 Peptide B Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000004576 lipid-binding Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 108010091748 peptide A Proteins 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- BJBUEDPLEOHJGE-UHFFFAOYSA-N (2R,3S)-3-Hydroxy-2-pyrolidinecarboxylic acid Natural products OC1CCNC1C(O)=O BJBUEDPLEOHJGE-UHFFFAOYSA-N 0.000 description 1
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- RWBOZUARFPJNQG-BYPYZUCNSA-N (2s)-2-amino-n-ethylbutanediamide Chemical compound CCNC(=O)[C@@H](N)CC(N)=O RWBOZUARFPJNQG-BYPYZUCNSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JHTPBGFVWWSHDL-UHFFFAOYSA-N 1,4-dichloro-2-isothiocyanatobenzene Chemical compound ClC1=CC=C(Cl)C(N=C=S)=C1 JHTPBGFVWWSHDL-UHFFFAOYSA-N 0.000 description 1
- RRWZZMHRVSMLCT-UHFFFAOYSA-N 2-(butylazaniumyl)acetate Chemical group CCCCNCC(O)=O RRWZZMHRVSMLCT-UHFFFAOYSA-N 0.000 description 1
- AHLFJIALFLSDAQ-UHFFFAOYSA-N 2-(pentylazaniumyl)acetate Chemical compound CCCCCNCC(O)=O AHLFJIALFLSDAQ-UHFFFAOYSA-N 0.000 description 1
- KCKPRRSVCFWDPX-UHFFFAOYSA-N 2-[methyl(pentyl)amino]acetic acid Chemical compound CCCCCN(C)CC(O)=O KCKPRRSVCFWDPX-UHFFFAOYSA-N 0.000 description 1
- XABCFXXGZPWJQP-UHFFFAOYSA-N 3-aminoadipic acid Chemical compound OC(=O)CC(N)CCC(O)=O XABCFXXGZPWJQP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- 150000000660 7-membered heterocyclic compounds Chemical class 0.000 description 1
- 101150063992 APOC2 gene Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 101800001401 Activation peptide Proteins 0.000 description 1
- 102400000069 Activation peptide Human genes 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 108010061118 Apolipoprotein A-V Proteins 0.000 description 1
- 102100040197 Apolipoprotein A-V Human genes 0.000 description 1
- 108010076807 Apolipoprotein C-I Proteins 0.000 description 1
- 102100036451 Apolipoprotein C-I Human genes 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101000619870 Bos taurus Lipoprotein lipase Proteins 0.000 description 1
- 102220466901 Breakpoint cluster region protein_R11K_mutation Human genes 0.000 description 1
- 101100298998 Caenorhabditis elegans pbs-3 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000016362 Catenins Human genes 0.000 description 1
- 108010067316 Catenins Proteins 0.000 description 1
- 102220548131 Cell division cycle-associated 7-like protein_F17A_mutation Human genes 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010014486 Elevated triglycerides Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101710195101 Flagellar filament outer layer protein Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102100030916 Gamma-soluble NSF attachment protein Human genes 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 102100026256 Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 1
- 101000702693 Homo sapiens Gamma-soluble NSF attachment protein Proteins 0.000 description 1
- 101001003882 Homo sapiens Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 Proteins 0.000 description 1
- 101001043185 Homo sapiens Lipase maturation factor 1 Proteins 0.000 description 1
- 101000619884 Homo sapiens Lipoprotein lipase Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- JUQLUIFNNFIIKC-YFKPBYRVSA-N L-2-aminopimelic acid Chemical compound OC(=O)[C@@H](N)CCCCC(O)=O JUQLUIFNNFIIKC-YFKPBYRVSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- AGPKZVBTJJNPAG-UHNVWZDZSA-N L-allo-Isoleucine Chemical compound CC[C@@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-UHNVWZDZSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
- DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical compound OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- UEQUQVLFIPOEMF-UHFFFAOYSA-N Mianserin Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical compound C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 description 1
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 1
- 108091005461 Nucleic proteins Chemical group 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010003581 Ribulose-bisphosphate carboxylase Proteins 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010043647 Thrombotic Stroke Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 210000000576 arachnoid Anatomy 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 102220356735 c.92A>G Human genes 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 229930002868 chlorophyll a Natural products 0.000 description 1
- 229930002869 chlorophyll b Natural products 0.000 description 1
- NSMUHPMZFPKNMZ-VBYMZDBQSA-M chlorophyll b Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C=O)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 NSMUHPMZFPKNMZ-VBYMZDBQSA-M 0.000 description 1
- BJBUEDPLEOHJGE-IUYQGCFVSA-N cis-3-hydroxy-D-proline zwitterion Chemical compound O[C@H]1CCN[C@H]1C(O)=O BJBUEDPLEOHJGE-IUYQGCFVSA-N 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000045903 human LPA Human genes 0.000 description 1
- 102000045312 human LPL Human genes 0.000 description 1
- 230000005661 hydrophobic surface Effects 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 208000037891 myocardial injury Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 102220004130 rs137854491 Human genes 0.000 description 1
- 238000013515 script Methods 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- YSMODUONRAFBET-WHFBIAKZSA-N threo-5-hydroxy-L-lysine Chemical compound NC[C@@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-WHFBIAKZSA-N 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 229960003732 tyramine Drugs 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- 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
- C07K14/775—Apolipopeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1722—Plasma globulins, lactoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
- C07K2319/41—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation containing a Myc-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
- C07K2319/42—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation containing a HA(hemagglutinin)-tag
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Marine Sciences & Fisheries (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762448358P | 2017-01-19 | 2017-01-19 | |
| US62/448,358 | 2017-01-19 | ||
| US201762476535P | 2017-03-24 | 2017-03-24 | |
| US201762476531P | 2017-03-24 | 2017-03-24 | |
| US62/476,531 | 2017-03-24 | ||
| US62/476,535 | 2017-03-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202130652A true TW202130652A (zh) | 2021-08-16 |
Family
ID=62908746
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW107102123A TWI788323B (zh) | 2017-01-19 | 2018-01-19 | Apoc-ii擬肽 |
| TW109138699A TW202130652A (zh) | 2017-01-19 | 2018-01-19 | Apoc-ii擬肽 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW107102123A TWI788323B (zh) | 2017-01-19 | 2018-01-19 | Apoc-ii擬肽 |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US11136372B2 (enExample) |
| EP (1) | EP3571216A4 (enExample) |
| JP (2) | JP7353973B2 (enExample) |
| KR (1) | KR102700862B1 (enExample) |
| CN (1) | CN110831957B (enExample) |
| AU (1) | AU2018210404B2 (enExample) |
| BR (1) | BR112019014707A2 (enExample) |
| CA (1) | CA3050106A1 (enExample) |
| IL (2) | IL268093B2 (enExample) |
| MX (1) | MX2019008529A (enExample) |
| NZ (1) | NZ755599A (enExample) |
| SG (2) | SG11201906422VA (enExample) |
| TW (2) | TWI788323B (enExample) |
| WO (1) | WO2018136803A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018136803A1 (en) | 2017-01-19 | 2018-07-26 | The United States Of America, As Represented By The Secretary Departmetn Of Health & Human Services | Apoc-ii mimetic peptides |
| CN117580857A (zh) * | 2021-06-23 | 2024-02-20 | 美国政府(由卫生和人类服务部的部长所代表) | Apoc-ii短模拟肽及使用方法 |
| WO2023215838A1 (en) * | 2022-05-05 | 2023-11-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Short apolipoprotein e mimetic peptides and methods of use |
| EP4565251A1 (en) * | 2022-08-07 | 2025-06-11 | Protean Bio, Inc. | Peptides for beta-cell survival and insulin production |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US6156727A (en) * | 1996-09-05 | 2000-12-05 | Uab Research Foundation | Anti-atherosclerotic peptides and a transgenic mouse model of antherosclerosis |
| MXPA04002848A (es) | 2001-09-28 | 2005-06-06 | Esperion Therapeutics Inc | Prevencion y tratamiento de restenosis por administracion local de medicamento. |
| US7220576B2 (en) * | 2002-01-07 | 2007-05-22 | Lifesensors, Inc. | Methods and compositions for protein expression and purification |
| CA2512879A1 (en) * | 2003-01-17 | 2004-08-12 | Soumya P. Sahoo | N-cyclohexylaminocarbonyl benzenesulfonamide derivatives |
| WO2005058938A2 (en) * | 2003-12-15 | 2005-06-30 | The Regents Of The University Of California | Helical synthetic peptides that stimulate cellular cholesterol efflux |
| US7691860B2 (en) * | 2004-02-19 | 2010-04-06 | Banyu Pharmaceutical Co., Ltd. | Sulfonamide derivatives |
| US7569546B2 (en) * | 2004-07-16 | 2009-08-04 | Trustees Of Tufts College | Apolipoprotein A1 mimetics and uses thereof |
| AU2006263332B2 (en) * | 2005-06-29 | 2012-02-23 | Hadasit Medical Research Services & Development Ltd. | Protein kinase C inhibitors for prevention of insulin resistance and type 2 diabetes |
| US20080138284A1 (en) * | 2006-09-26 | 2008-06-12 | Lipid Sciences, Inc. | Novel Peptides That Promote Lipid Efflux |
| WO2009097584A1 (en) * | 2008-01-30 | 2009-08-06 | Proteogenix, Inc. | Maternal serum biomarkers for detection of pre-eclampsia |
| WO2009129263A1 (en) * | 2008-04-15 | 2009-10-22 | The Government Of The Usa As Represented By The Secretary Of The Department Of Health & Human Serv. | Peptides promoting lipid efflux via abca1 and activating a lipoprotein lipase |
| EP2484692A4 (en) | 2009-09-30 | 2013-03-06 | Snu R&Db Foundation | MIMETIC APOLIPOPROTEIN A-1-PEPTIDES AND THERAPEUTICS FOR THE TREATMENT OF HYPERLIPIDEMIA AND DISEASES RELATED TO HYPERLIPIDEMIA THEREWITH |
| BR112015010276A2 (pt) | 2012-11-06 | 2019-10-15 | Hoffmann La Roche | peptídeos miméticos |
| WO2018136803A1 (en) | 2017-01-19 | 2018-07-26 | The United States Of America, As Represented By The Secretary Departmetn Of Health & Human Services | Apoc-ii mimetic peptides |
| EA201991491A1 (ru) | 2017-03-24 | 2019-12-30 | Дзе Юнайтед Стейтс Оф Америка, Эз Репрезентед Бай Дзе Секретари, Департмент Оф Хелс Энд Хьюман Сервисис | Миметические пептиды apoc-ii |
-
2018
- 2018-01-19 WO PCT/US2018/014532 patent/WO2018136803A1/en not_active Ceased
- 2018-01-19 SG SG11201906422VA patent/SG11201906422VA/en unknown
- 2018-01-19 BR BR112019014707A patent/BR112019014707A2/pt unknown
- 2018-01-19 US US16/479,183 patent/US11136372B2/en active Active
- 2018-01-19 JP JP2019539809A patent/JP7353973B2/ja active Active
- 2018-01-19 CN CN201880019604.7A patent/CN110831957B/zh active Active
- 2018-01-19 MX MX2019008529A patent/MX2019008529A/es unknown
- 2018-01-19 AU AU2018210404A patent/AU2018210404B2/en active Active
- 2018-01-19 EP EP18742118.5A patent/EP3571216A4/en active Pending
- 2018-01-19 IL IL268093A patent/IL268093B2/en unknown
- 2018-01-19 SG SG10201911974UA patent/SG10201911974UA/en unknown
- 2018-01-19 NZ NZ755599A patent/NZ755599A/en unknown
- 2018-01-19 TW TW107102123A patent/TWI788323B/zh active
- 2018-01-19 KR KR1020197024024A patent/KR102700862B1/ko active Active
- 2018-01-19 TW TW109138699A patent/TW202130652A/zh unknown
- 2018-01-19 CA CA3050106A patent/CA3050106A1/en active Pending
-
2020
- 2020-12-29 IL IL279831A patent/IL279831A/en unknown
-
2021
- 2021-03-09 US US17/195,766 patent/US11827690B2/en active Active
-
2023
- 2023-06-19 JP JP2023100171A patent/JP2023116739A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| MX2019008529A (es) | 2020-02-07 |
| AU2018210404A1 (en) | 2019-08-08 |
| SG10201911974UA (en) | 2020-02-27 |
| US20200140522A1 (en) | 2020-05-07 |
| NZ755599A (en) | 2022-12-23 |
| WO2018136803A1 (en) | 2018-07-26 |
| IL279831A (en) | 2021-03-01 |
| JP7353973B2 (ja) | 2023-10-02 |
| AU2018210404B2 (en) | 2022-01-27 |
| IL268093B1 (en) | 2024-03-01 |
| TWI788323B (zh) | 2023-01-01 |
| IL268093A (en) | 2019-09-26 |
| TW201835097A (zh) | 2018-10-01 |
| IL268093B2 (en) | 2024-07-01 |
| EP3571216A1 (en) | 2019-11-27 |
| SG11201906422VA (en) | 2019-08-27 |
| BR112019014707A2 (pt) | 2020-04-07 |
| EP3571216A4 (en) | 2020-11-04 |
| KR102700862B1 (ko) | 2024-08-30 |
| US11827690B2 (en) | 2023-11-28 |
| CA3050106A1 (en) | 2018-07-26 |
| US20210324043A1 (en) | 2021-10-21 |
| JP2020511425A (ja) | 2020-04-16 |
| WO2018136803A8 (en) | 2019-08-01 |
| US11136372B2 (en) | 2021-10-05 |
| JP2023116739A (ja) | 2023-08-22 |
| CN110831957B (zh) | 2024-02-09 |
| KR20190121305A (ko) | 2019-10-25 |
| CN110831957A (zh) | 2020-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11827690B2 (en) | ApoC-II mimetic peptides | |
| CN107074923B (zh) | Apoe模拟肽及对清除血浆胆固醇的较高效力 | |
| US9815869B2 (en) | SP-B and SP-C peptides, synthetic lung surfactants, and use thereof | |
| TW201629085A (zh) | 芋螺毒素（ｃｏｎｏｔｏｘｉｎ）肽之修飾及用途 | |
| JP2020523035A (ja) | タウ凝集阻害剤 | |
| JP2019089834A (ja) | アポリポタンパク質模倣体及びその使用 | |
| AU2018318319A1 (en) | Tau aggregation peptide inhibitors | |
| TW202204375A (zh) | 治療冠狀病毒感染之方法 | |
| EA042134B1 (ru) | МИМЕТИЧЕСКИЕ ПЕПТИДЫ apoC-II | |
| CN117580857A (zh) | Apoc-ii短模拟肽及使用方法 | |
| US20170305981A1 (en) | Synthetic peptides | |
| WO2025172720A1 (en) | Fragment of complement factor h related protein 5 which restores complement regulation | |
| HK1242718A1 (en) | Apoe mimetic peptides and higher potency to clear plasma cholesterol | |
| WO2005118630A2 (en) | Peptides for the treatment of diabetes |