CA2455985A1 - Inhibiteur therapeutique des cellules vasculaires du muscle lisse - Google Patents
Inhibiteur therapeutique des cellules vasculaires du muscle lisse Download PDFInfo
- Publication number
- CA2455985A1 CA2455985A1 CA002455985A CA2455985A CA2455985A1 CA 2455985 A1 CA2455985 A1 CA 2455985A1 CA 002455985 A CA002455985 A CA 002455985A CA 2455985 A CA2455985 A CA 2455985A CA 2455985 A1 CA2455985 A1 CA 2455985A1
- Authority
- CA
- Canada
- Prior art keywords
- tgf
- beta
- smooth muscle
- cells
- proliferation
- 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.)
- Abandoned
Links
- 210000004509 vascular smooth muscle cell Anatomy 0.000 title claims abstract description 244
- 229940124788 therapeutic inhibitor Drugs 0.000 title description 2
- 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 abstract description 283
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims abstract description 280
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims abstract description 280
- 230000035755 proliferation Effects 0.000 claims abstract description 117
- 239000002552 dosage form Substances 0.000 claims abstract description 63
- 238000013508 migration Methods 0.000 claims abstract description 47
- 239000012730 sustained-release form Substances 0.000 claims abstract description 45
- 230000005012 migration Effects 0.000 claims abstract description 44
- 238000013268 sustained release Methods 0.000 claims abstract description 44
- 238000004519 manufacturing process Methods 0.000 claims abstract description 40
- 238000002399 angioplasty Methods 0.000 claims abstract description 38
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 36
- 208000014674 injury Diseases 0.000 claims abstract description 36
- 239000012190 activator Substances 0.000 claims abstract description 28
- 230000023750 transforming growth factor beta production Effects 0.000 claims abstract description 26
- 230000002792 vascular Effects 0.000 claims abstract description 26
- 230000008733 trauma Effects 0.000 claims abstract description 25
- 208000037803 restenosis Diseases 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 206010020772 Hypertension Diseases 0.000 claims abstract description 7
- 210000000056 organ Anatomy 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims description 300
- 239000003814 drug Substances 0.000 claims description 120
- 238000000034 method Methods 0.000 claims description 52
- 230000005764 inhibitory process Effects 0.000 claims description 41
- 230000002401 inhibitory effect Effects 0.000 claims description 37
- 230000004663 cell proliferation Effects 0.000 claims description 34
- 230000003902 lesion Effects 0.000 claims description 30
- 230000015572 biosynthetic process Effects 0.000 claims description 27
- 230000022131 cell cycle Effects 0.000 claims description 21
- 230000001603 reducing effect Effects 0.000 claims description 17
- 108020004999 messenger RNA Proteins 0.000 claims description 15
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 14
- 230000036262 stenosis Effects 0.000 claims description 14
- 208000037804 stenosis Diseases 0.000 claims description 14
- 230000006372 lipid accumulation Effects 0.000 claims description 11
- 230000001575 pathological effect Effects 0.000 claims description 11
- 230000009467 reduction Effects 0.000 claims description 9
- 230000003143 atherosclerotic effect Effects 0.000 claims description 8
- 238000001356 surgical procedure Methods 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000015590 smooth muscle cell migration Effects 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 239000011859 microparticle Substances 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 239000002105 nanoparticle Substances 0.000 claims description 2
- 230000000472 traumatic effect Effects 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 claims 1
- 230000003144 traumatizing effect Effects 0.000 claims 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 abstract description 94
- 230000002829 reductive effect Effects 0.000 abstract description 20
- 230000000069 prophylactic effect Effects 0.000 abstract description 7
- 230000002159 abnormal effect Effects 0.000 abstract description 4
- 231100000057 systemic toxicity Toxicity 0.000 abstract description 3
- 241000124008 Mammalia Species 0.000 abstract description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 216
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 110
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 109
- 229960001603 tamoxifen Drugs 0.000 description 108
- 229940124597 therapeutic agent Drugs 0.000 description 99
- 230000000694 effects Effects 0.000 description 98
- 229920000669 heparin Polymers 0.000 description 59
- 229960002897 heparin Drugs 0.000 description 59
- 239000003795 chemical substances by application Substances 0.000 description 58
- 239000002609 medium Substances 0.000 description 56
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 55
- 230000006820 DNA synthesis Effects 0.000 description 47
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 46
- 241000699670 Mus sp. Species 0.000 description 45
- 230000004913 activation Effects 0.000 description 45
- 241000700159 Rattus Species 0.000 description 41
- 238000003556 assay Methods 0.000 description 38
- 108010088842 Fibrinolysin Proteins 0.000 description 37
- 210000002966 serum Anatomy 0.000 description 37
- 230000001965 increasing effect Effects 0.000 description 36
- 229940012957 plasmin Drugs 0.000 description 36
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 34
- 239000012894 fetal calf serum Substances 0.000 description 34
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 33
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 33
- 210000001367 artery Anatomy 0.000 description 32
- 230000002062 proliferating effect Effects 0.000 description 32
- 150000002632 lipids Chemical class 0.000 description 31
- 239000003112 inhibitor Substances 0.000 description 30
- 102000014914 Carrier Proteins Human genes 0.000 description 28
- 108091008324 binding proteins Proteins 0.000 description 28
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 28
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 27
- 238000007792 addition Methods 0.000 description 27
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 27
- 230000001225 therapeutic effect Effects 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 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 26
- 239000002953 phosphate buffered saline Substances 0.000 description 26
- 210000001519 tissue Anatomy 0.000 description 26
- JVHIPYJQMFNCEK-UHFFFAOYSA-N cytochalasin Natural products N1C(=O)C2(C(C=CC(C)CC(C)CC=C3)OC(C)=O)C3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 JVHIPYJQMFNCEK-UHFFFAOYSA-N 0.000 description 25
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 24
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 24
- 102000013566 Plasminogen Human genes 0.000 description 24
- 108010051456 Plasminogen Proteins 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 24
- 239000011159 matrix material Substances 0.000 description 22
- 238000011282 treatment Methods 0.000 description 22
- 210000002460 smooth muscle Anatomy 0.000 description 21
- 102000004264 Osteopontin Human genes 0.000 description 20
- 108010081689 Osteopontin Proteins 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 20
- 230000008602 contraction Effects 0.000 description 19
- 210000002744 extracellular matrix Anatomy 0.000 description 19
- 239000002245 particle Substances 0.000 description 19
- 108090000765 processed proteins & peptides Proteins 0.000 description 19
- 230000001028 anti-proliverative effect Effects 0.000 description 18
- 230000027455 binding Effects 0.000 description 18
- 210000002464 muscle smooth vascular Anatomy 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 17
- 210000000709 aorta Anatomy 0.000 description 17
- 238000010790 dilution Methods 0.000 description 17
- 239000012895 dilution Substances 0.000 description 17
- 230000000638 stimulation Effects 0.000 description 17
- 102000007469 Actins Human genes 0.000 description 16
- 108010085238 Actins Proteins 0.000 description 16
- 239000000824 cytostatic agent Substances 0.000 description 16
- 239000002254 cytotoxic agent Substances 0.000 description 16
- 229940127089 cytotoxic agent Drugs 0.000 description 16
- 231100000599 cytotoxic agent Toxicity 0.000 description 16
- 230000014509 gene expression Effects 0.000 description 16
- 239000003102 growth factor Substances 0.000 description 16
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 16
- 229930012538 Paclitaxel Natural products 0.000 description 15
- 230000003247 decreasing effect Effects 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 229960001592 paclitaxel Drugs 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 239000003656 tris buffered saline Substances 0.000 description 15
- 108010007622 LDL Lipoproteins Proteins 0.000 description 14
- 102000007330 LDL Lipoproteins Human genes 0.000 description 14
- 230000035508 accumulation Effects 0.000 description 13
- 238000009825 accumulation Methods 0.000 description 13
- 230000007423 decrease Effects 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 210000002950 fibroblast Anatomy 0.000 description 13
- 230000012010 growth Effects 0.000 description 13
- 238000002372 labelling Methods 0.000 description 13
- 210000003668 pericyte Anatomy 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 230000003305 autocrine Effects 0.000 description 12
- 230000001413 cellular effect Effects 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 239000000562 conjugate Substances 0.000 description 12
- SDZRWUKZFQQKKV-JHADDHBZSA-N cytochalasin D Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@H]\3[C@]2([C@@H](/C=C/[C@@](C)(O)C(=O)[C@@H](C)C/C=C/3)OC(C)=O)C(=O)N1)=C)C)C1=CC=CC=C1 SDZRWUKZFQQKKV-JHADDHBZSA-N 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 238000007828 protein synthesis assay Methods 0.000 description 12
- 230000014616 translation Effects 0.000 description 12
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 11
- 208000027418 Wounds and injury Diseases 0.000 description 11
- 230000009471 action Effects 0.000 description 11
- 229940098773 bovine serum albumin Drugs 0.000 description 11
- ZMAODHOXRBLOQO-UHFFFAOYSA-N cytochalasin-A Natural products N1C(=O)C23OC(=O)C=CC(=O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 ZMAODHOXRBLOQO-UHFFFAOYSA-N 0.000 description 11
- 230000006378 damage Effects 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- 230000007246 mechanism Effects 0.000 description 11
- 230000002265 prevention Effects 0.000 description 11
- 238000001243 protein synthesis Methods 0.000 description 11
- 108010059480 Chondroitin Sulfate Proteoglycans Proteins 0.000 description 10
- 102000005598 Chondroitin Sulfate Proteoglycans Human genes 0.000 description 10
- 241000699660 Mus musculus Species 0.000 description 10
- 230000003472 neutralizing effect Effects 0.000 description 10
- 235000021590 normal diet Nutrition 0.000 description 10
- 230000037361 pathway Effects 0.000 description 10
- 238000011830 transgenic mouse model Methods 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 239000003636 conditioned culture medium Substances 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 206010020718 hyperplasia Diseases 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 230000028327 secretion Effects 0.000 description 9
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 8
- 229950004398 broxuridine Drugs 0.000 description 8
- 230000001684 chronic effect Effects 0.000 description 8
- 231100000409 cytocidal Toxicity 0.000 description 8
- 230000000445 cytocidal effect Effects 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 238000010348 incorporation Methods 0.000 description 8
- 239000003226 mitogen Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 208000010125 myocardial infarction Diseases 0.000 description 8
- 229940063683 taxotere Drugs 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 7
- 108010029485 Protein Isoforms Proteins 0.000 description 7
- 102000001708 Protein Isoforms Human genes 0.000 description 7
- 241000282887 Suidae Species 0.000 description 7
- 206010057469 Vascular stenosis Diseases 0.000 description 7
- 230000002095 anti-migrative effect Effects 0.000 description 7
- 230000001143 conditioned effect Effects 0.000 description 7
- 210000004351 coronary vessel Anatomy 0.000 description 7
- 230000001085 cytostatic effect Effects 0.000 description 7
- 230000001472 cytotoxic effect Effects 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 238000011068 loading method Methods 0.000 description 7
- 230000007170 pathology Effects 0.000 description 7
- 239000004033 plastic Substances 0.000 description 7
- 229920003023 plastic Polymers 0.000 description 7
- 230000004936 stimulating effect Effects 0.000 description 7
- 229930013292 trichothecene Natural products 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 108020004635 Complementary DNA Proteins 0.000 description 6
- NAIODHJWOHMDJX-UHFFFAOYSA-N Cytochalasin C Natural products N1C(=O)C23C(OC(C)=O)C=CC(C)(O)C(=O)C(C)CC=CC2C(O)C(C)=C(C)C3C1CC1=CC=CC=C1 NAIODHJWOHMDJX-UHFFFAOYSA-N 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 6
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 6
- 230000018199 S phase Effects 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 102000004060 Transforming Growth Factor-beta Type II Receptor Human genes 0.000 description 6
- 108010082684 Transforming Growth Factor-beta Type II Receptor Proteins 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 230000032823 cell division Effects 0.000 description 6
- NAIODHJWOHMDJX-NGFXLRBHSA-N cytochalasin c Chemical compound C1([C@@H]2C(C)=C(C)[C@@H](O)[C@@H]3\C=C/C[C@@H](C([C@](C)(O)\C=C/[C@@H](OC(C)=O)[C@]32C(=O)N1)=O)C)CC1=CC=CC=C1 NAIODHJWOHMDJX-NGFXLRBHSA-N 0.000 description 6
- 231100000433 cytotoxic Toxicity 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 210000001105 femoral artery Anatomy 0.000 description 6
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 6
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000002147 killing effect Effects 0.000 description 6
- 239000004816 latex Substances 0.000 description 6
- 229920000126 latex Polymers 0.000 description 6
- 230000002503 metabolic effect Effects 0.000 description 6
- 210000003632 microfilament Anatomy 0.000 description 6
- 230000002297 mitogenic effect Effects 0.000 description 6
- 230000000877 morphologic effect Effects 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 210000004231 tunica media Anatomy 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108010039627 Aprotinin Proteins 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 5
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 5
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 229960004405 aprotinin Drugs 0.000 description 5
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000004087 circulation Effects 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 208000029078 coronary artery disease Diseases 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 239000007850 fluorescent dye Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 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 5
- 201000010260 leiomyoma Diseases 0.000 description 5
- 230000033885 plasminogen activation Effects 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 229930183944 roridin Natural products 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 5
- 229960005314 suramin Drugs 0.000 description 5
- 230000002459 sustained effect Effects 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 231100000216 vascular lesion Toxicity 0.000 description 5
- 230000006442 vascular tone Effects 0.000 description 5
- 229930190906 verrucarin Natural products 0.000 description 5
- 229920000936 Agarose Polymers 0.000 description 4
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 4
- 108010081589 Becaplermin Proteins 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 108060005980 Collagenase Proteins 0.000 description 4
- 102000029816 Collagenase Human genes 0.000 description 4
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 4
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 4
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 241000233866 Fungi Species 0.000 description 4
- 230000005526 G1 to G0 transition Effects 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 102000004895 Lipoproteins Human genes 0.000 description 4
- 108090001030 Lipoproteins Proteins 0.000 description 4
- 102100039809 Matrix Gla protein Human genes 0.000 description 4
- 108091022875 Microtubule Proteins 0.000 description 4
- 102000029749 Microtubule Human genes 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 102000001938 Plasminogen Activators Human genes 0.000 description 4
- 108010001014 Plasminogen Activators Proteins 0.000 description 4
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 208000024248 Vascular System injury Diseases 0.000 description 4
- 208000012339 Vascular injury Diseases 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 230000012292 cell migration Effects 0.000 description 4
- 229960002424 collagenase Drugs 0.000 description 4
- 230000002860 competitive effect Effects 0.000 description 4
- 238000007887 coronary angioplasty Methods 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 208000030533 eye disease Diseases 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 208000013403 hyperactivity Diseases 0.000 description 4
- 238000010191 image analysis Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 230000033001 locomotion Effects 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000004688 microtubule Anatomy 0.000 description 4
- 230000008520 organization Effects 0.000 description 4
- 102000013415 peroxidase activity proteins Human genes 0.000 description 4
- 108040007629 peroxidase activity proteins Proteins 0.000 description 4
- 229940127126 plasminogen activator Drugs 0.000 description 4
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 239000003909 protein kinase inhibitor Substances 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 210000003705 ribosome Anatomy 0.000 description 4
- 210000001082 somatic cell Anatomy 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 230000002966 stenotic effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- LZAJKCZTKKKZNT-PMNGPLLRSA-N trichothecene Chemical compound C12([C@@]3(CC[C@H]2OC2C=C(CCC23C)C)C)CO1 LZAJKCZTKKKZNT-PMNGPLLRSA-N 0.000 description 4
- GOTYCQXAAKQUOD-VINXHBPISA-N (1R,3R,8R,12S,13R,18E,20E,24R,25S,26S)-12-hydroxy-5,13,25-trimethylspiro[2,10,16,23-tetraoxatetracyclo[22.2.1.03,8.08,25]heptacosa-4,18,20-triene-26,2'-oxirane]-6,11,17,22-tetrone Chemical compound C[C@@H]1CCOC(=O)/C=C/C=C/C(=O)O[C@@H]2C[C@@H]3[C@]4([C@]2([C@]5(CC(=O)C(=C[C@H]5O3)C)COC(=O)[C@H]1O)C)CO4 GOTYCQXAAKQUOD-VINXHBPISA-N 0.000 description 3
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 3
- 102000002585 Contractile Proteins Human genes 0.000 description 3
- 108010068426 Contractile Proteins Proteins 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 3
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- 102000005720 Glutathione transferase Human genes 0.000 description 3
- 108010070675 Glutathione transferase Proteins 0.000 description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
- 206010020880 Hypertrophy Diseases 0.000 description 3
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 3
- 102000000853 LDL receptors Human genes 0.000 description 3
- 108010001831 LDL receptors Proteins 0.000 description 3
- 102000057248 Lipoprotein(a) Human genes 0.000 description 3
- 108010033266 Lipoprotein(a) Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102000002151 Microfilament Proteins Human genes 0.000 description 3
- 108010040897 Microfilament Proteins Proteins 0.000 description 3
- 231100000678 Mycotoxin Toxicity 0.000 description 3
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 3
- 239000000006 Nitroglycerin Substances 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 108010067372 Pancreatic elastase Proteins 0.000 description 3
- 102000016387 Pancreatic elastase Human genes 0.000 description 3
- 241001504519 Papio ursinus Species 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 3
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 3
- 102400000716 Transforming growth factor beta-1 Human genes 0.000 description 3
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000036523 atherogenesis Effects 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 210000001715 carotid artery Anatomy 0.000 description 3
- 229960001338 colchicine Drugs 0.000 description 3
- 210000002808 connective tissue Anatomy 0.000 description 3
- 230000003436 cytoskeletal effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 229940126864 fibroblast growth factor Drugs 0.000 description 3
- 238000000799 fluorescence microscopy Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 229960003711 glyceryl trinitrate Drugs 0.000 description 3
- 230000002706 hydrostatic effect Effects 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 238000012744 immunostaining Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000011278 mitosis Effects 0.000 description 3
- 230000003387 muscular Effects 0.000 description 3
- 239000002636 mycotoxin Substances 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000014508 negative regulation of coagulation Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- -1 nitroglycerin Chemical class 0.000 description 3
- 230000036963 noncompetitive effect Effects 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000002806 plasmin inhibitor Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000007115 recruitment Effects 0.000 description 3
- 238000003118 sandwich ELISA Methods 0.000 description 3
- 239000002689 soil Substances 0.000 description 3
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 3
- 229960000187 tissue plasminogen activator Drugs 0.000 description 3
- 150000003327 trichothecene derivatives Chemical class 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- LZAJKCZTKKKZNT-QMIVOQANSA-N 12,13-epoxytrichothec-9-ene Chemical compound C([C@@]12[C@@]3(CC[C@H]1O[C@@H]1C=C(CC[C@@]13C)C)C)O2 LZAJKCZTKKKZNT-QMIVOQANSA-N 0.000 description 2
- NAEWXXDGBKTIMN-OWTACEMYSA-N 53760-19-3 Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@H]\3[C@]2([C@@H](/C=C/[C@](C)(O)C[C@@H](C)C/C=C/3)OC(C)=O)C(=O)N1)=C)C)C1=CC=CC=C1 NAEWXXDGBKTIMN-OWTACEMYSA-N 0.000 description 2
- 241001103808 Albifimbria verrucaria Species 0.000 description 2
- 102400000345 Angiotensin-2 Human genes 0.000 description 2
- 101800000733 Angiotensin-2 Proteins 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- 108010012927 Apoprotein(a) Proteins 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- KPQRGEZMOJERCR-UHFFFAOYSA-N Cytochalasin Qpho Natural products N1C(=O)C2(C(C=CC(C)(O)CC(C)CC=C3)O)C3C(O)C(O)(C)C(C)C2C1CC1=CC=CC=C1 KPQRGEZMOJERCR-UHFFFAOYSA-N 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 108010014258 Elastin Proteins 0.000 description 2
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- 208000018142 Leiomyosarcoma Diseases 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 2
- 108010084498 Myosin Heavy Chains Proteins 0.000 description 2
- 241000223251 Myrothecium Species 0.000 description 2
- BNQSTAOJRULKNX-UHFFFAOYSA-N N-(6-acetamidohexyl)acetamide Chemical compound CC(=O)NCCCCCCNC(C)=O BNQSTAOJRULKNX-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 241000772415 Neovison vison Species 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 2
- 208000012868 Overgrowth Diseases 0.000 description 2
- 229940122791 Plasmin inhibitor Drugs 0.000 description 2
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 2
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 241000589516 Pseudomonas Species 0.000 description 2
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 2
- NSFWWJIQIKBZMJ-YKNYLIOZSA-N Roridin A Chemical compound C([C@]12[C@]3(C)[C@H]4C[C@H]1O[C@@H]1C=C(C)CC[C@@]13COC(=O)[C@@H](O)[C@H](C)CCO[C@H](\C=C\C=C/C(=O)O4)[C@H](O)C)O2 NSFWWJIQIKBZMJ-YKNYLIOZSA-N 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 206010046798 Uterine leiomyoma Diseases 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 229950006323 angiotensin ii Drugs 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- GCIKKGSNXSCKCP-UHFFFAOYSA-N aspochalasin C or D Natural products C1=C(C)CCC(O)C(O)C=CC(=O)C23C1C=C(C)C(C)C2C(CC(C)C)NC3=O GCIKKGSNXSCKCP-UHFFFAOYSA-N 0.000 description 2
- GCIKKGSNXSCKCP-PJWJRCBPSA-N aspochalasin c Chemical compound C(/[C@H](O)[C@@H](O)CC/C(C)=C/1)=C\C(=O)[C@]23[C@@H]\1C=C(C)[C@@H](C)[C@H]2[C@H](CC(C)C)NC3=O GCIKKGSNXSCKCP-PJWJRCBPSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 238000006065 biodegradation reaction Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 102000006783 calponin Human genes 0.000 description 2
- 108010086826 calponin Proteins 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 230000011748 cell maturation Effects 0.000 description 2
- 238000002737 cell proliferation kit Methods 0.000 description 2
- 230000019522 cellular metabolic process Effects 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- OUMWCYMRLMEZJH-VOXRAUTJSA-N chaetoglobosin A Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)[C@@H]1[C@@H]([C@]2(O[C@H]22)C)C)C(=O)[C@@]11[C@H]2\C=C\C[C@H](C)\C=C(C)\[C@@H](O)C(=O)\C=C\C1=O OUMWCYMRLMEZJH-VOXRAUTJSA-N 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 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 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 230000006957 competitive inhibition Effects 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- OCZJGPJVAQGKFA-UHFFFAOYSA-N cytochalasin H Natural products N1C(=O)C2(C(C=CC(C)(O)CC(C)CC=C3)OC(C)=O)C3C=C(CO)C(C)C2C1CC1=CC=CC=C1 OCZJGPJVAQGKFA-UHFFFAOYSA-N 0.000 description 2
- HMZOTJQYCSCDHG-UHFFFAOYSA-N cytochalasin U Natural products N1C(=O)C23OOC(=O)CC4OC4=C(C=O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 HMZOTJQYCSCDHG-UHFFFAOYSA-N 0.000 description 2
- 108091092330 cytoplasmic RNA Proteins 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 230000010339 dilation Effects 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 230000001909 effect on DNA Effects 0.000 description 2
- 230000000431 effect on proliferation Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000001215 fluorescent labelling Methods 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000000394 mitotic effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000007491 morphometric analysis Methods 0.000 description 2
- 210000003365 myofibril Anatomy 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000000863 peptide conjugate Substances 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- IMUQLZLGWJSVMV-UOBFQKKOSA-N roridin A Natural products CC(O)C1OCCC(C)C(O)C(=O)OCC2CC(=CC3OC4CC(OC(=O)C=C/C=C/1)C(C)(C23)C45CO5)C IMUQLZLGWJSVMV-UOBFQKKOSA-N 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 208000010485 smooth muscle tumor Diseases 0.000 description 2
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 230000002885 thrombogenetic effect Effects 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000008736 traumatic injury Effects 0.000 description 2
- 208000010579 uterine corpus leiomyoma Diseases 0.000 description 2
- 201000007954 uterine fibroid Diseases 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000003260 vortexing Methods 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- OUMWCYMRLMEZJH-UHFFFAOYSA-N (13E,17E,21E)-6,7beta-epoxy-19beta-hydroxy-10-indol-3-yl-16alpha,18-dimethyl-[13]cytochalasa-13,17,21-triene-1,20,23-trione Natural products C12OC2(C)C(C)C2C(CC=3C4=CC=CC=C4NC=3)NC(=O)C22C1C=CCC(C)C=C(C)C(O)C(=O)C=CC2=O OUMWCYMRLMEZJH-UHFFFAOYSA-N 0.000 description 1
- KXUADWPFUZOYLZ-PDFJPCBASA-N (1S,6S,8E,10S,12E,14S,15S,17R,18S,19S,20S)-20-benzyl-6-hydroxy-8,10,17,18-tetramethyl-2,16-dioxa-21-azatetracyclo[12.8.0.01,19.015,17]docosa-8,12-diene-3,7,22-trione Chemical compound C[C@H]1[C@H]2[C@H](Cc3ccccc3)NC(=O)[C@]22OC(=O)CC[C@H](O)C(=O)\C(C)=C\[C@@H](C)C\C=C\[C@H]2[C@@H]2O[C@]12C KXUADWPFUZOYLZ-PDFJPCBASA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- 101710175516 14 kDa zinc-binding protein Proteins 0.000 description 1
- ODSNARDHJFFSRH-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical group C1CCCC2CNCC21 ODSNARDHJFFSRH-UHFFFAOYSA-N 0.000 description 1
- WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 1
- ZUYKJZQOPXDNOK-UHFFFAOYSA-N 2-(ethylamino)-2-thiophen-2-ylcyclohexan-1-one;hydrochloride Chemical compound Cl.C=1C=CSC=1C1(NCC)CCCCC1=O ZUYKJZQOPXDNOK-UHFFFAOYSA-N 0.000 description 1
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- VUEFRYQBOMQOMV-CGCQETNGSA-N 7,19-dihydroxy-10-(1h-indol-3-yl)-16,18-dimethyl-(7s,13e,16s,17e,19r,21e)-(13)cytochalasa-5,13,17,21-tetraene-1,20,23-trione Chemical compound O=C1\C=C\C(=O)[C@H](O)\C(C)=C/[C@@H](C)C\C=C\[C@H]2[C@H](O)C(C)=C(C)[C@@H]3[C@@]21C(=O)N[C@H]3CC1=CNC2=CC=CC=C12 VUEFRYQBOMQOMV-CGCQETNGSA-N 0.000 description 1
- PBCZSGKMGDDXIJ-HQCWYSJUSA-N 7-hydroxystaurosporine Chemical compound N([C@H](O)C1=C2C3=CC=CC=C3N3C2=C24)C(=O)C1=C2C1=CC=CC=C1N4[C@H]1C[C@@H](NC)[C@@H](OC)[C@]3(C)O1 PBCZSGKMGDDXIJ-HQCWYSJUSA-N 0.000 description 1
- YGKUXRWMCOUTAL-LGUVXVKNSA-N 70852-29-8 Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)[C@@H]1[C@@H]([C@]2(O[C@H]22)C)C)C(=O)[C@@]11[C@H]2\C=C\C[C@H](C)CC(=O)CCC1=O YGKUXRWMCOUTAL-LGUVXVKNSA-N 0.000 description 1
- BVKOTAZOMFVYMH-YBCLPTENSA-N 72363-47-4 Chemical compound O=C([C@@H](O)CC\C(C)=C/1)\C=C/C(=O)[C@]23[C@@H]\1C=C(C)[C@@H](C)[C@H]2[C@H](CC(C)C)NC3=O BVKOTAZOMFVYMH-YBCLPTENSA-N 0.000 description 1
- AZWOSJCABFILKS-XZRSCLCVSA-N 79648-72-9 Chemical compound C([C@H]1[C@@H]2[C@@H]([C@]3(O[C@H]3[C@H]\3[C@]2(C(/C=C/C(=O)[C@H](OC(C)=O)\C(C)=C/[C@@H](C)C/C=C/3)=O)C(=O)N1)C)C)C1=CC=CC=C1 AZWOSJCABFILKS-XZRSCLCVSA-N 0.000 description 1
- PBCZSGKMGDDXIJ-UHFFFAOYSA-N 7beta-hydroxystaurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3C(O)NC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 PBCZSGKMGDDXIJ-UHFFFAOYSA-N 0.000 description 1
- 101710092934 Actin, cytoskeletal Proteins 0.000 description 1
- 102000004888 Aquaporin 1 Human genes 0.000 description 1
- 108090001004 Aquaporin 1 Proteins 0.000 description 1
- 241000408939 Atalopedes campestris Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 238000007809 Boyden Chamber assay Methods 0.000 description 1
- YOSIWRQXBHJIKL-ZRLLFBEYSA-N C[C@H]1[C@H]2[C@H](Cc3ccccc3)NC(=O)[C@@]22[C@@H](\C=C/C[C@H](C)C(=O)[C@@H](C)\C=C/[C@H]2OC(C)=O)[C@H](O)C1=C Chemical compound C[C@H]1[C@H]2[C@H](Cc3ccccc3)NC(=O)[C@@]22[C@@H](\C=C/C[C@H](C)C(=O)[C@@H](C)\C=C/[C@H]2OC(C)=O)[C@H](O)C1=C YOSIWRQXBHJIKL-ZRLLFBEYSA-N 0.000 description 1
- VFEKKHXLJKMKBO-RSTZQMKSSA-N C[C@H]1[C@H]2[C@H](Cc3ccccc3)NC(=O)[C@@]22[C@H](C=C1C)\C=C/C[C@H](C)C(=O)[C@](C)(O)\C=C/[C@H]2OC(C)=O Chemical compound C[C@H]1[C@H]2[C@H](Cc3ccccc3)NC(=O)[C@@]22[C@H](C=C1C)\C=C/C[C@H](C)C(=O)[C@](C)(O)\C=C/[C@H]2OC(C)=O VFEKKHXLJKMKBO-RSTZQMKSSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- VUEFRYQBOMQOMV-UHFFFAOYSA-N Chaetoglobosin B Natural products O=C1C=CC(=O)C(O)C(C)=CC(C)CC=CC2C(O)C(C)=C(C)C3C21C(=O)NC3CC1=CNC2=CC=CC=C12 VUEFRYQBOMQOMV-UHFFFAOYSA-N 0.000 description 1
- FTBNYQWFSWKCKW-UHFFFAOYSA-N Chaetoglobosin D Natural products OC1C(=C)C(C)C2C(CC=3C4=CC=CC=C4NC=3)NC(=O)C22C1C=CCC(C)C=C(C)C(O)C(=O)C=CC2=O FTBNYQWFSWKCKW-UHFFFAOYSA-N 0.000 description 1
- XSYISNGSIFFBMR-UHFFFAOYSA-N Chaetoglobosin J Natural products N1C(=O)C2(C(C=CC(=O)C(O)C(C)=CC(C)CC=C3)=O)C3C=C(C)C(C)C2C1CC1=CNC2=CC=CC=C12 XSYISNGSIFFBMR-UHFFFAOYSA-N 0.000 description 1
- RSYKJHLWNMXRKZ-UHFFFAOYSA-N Chaetoglobosin K Natural products C12OC2(C)C(CC)C2C(C(C)C=3C4=CC=CC=C4NC=3)NC(=O)C22C1C=CCC(C)C=C(C)C(O)C(=O)C=CC2=O RSYKJHLWNMXRKZ-UHFFFAOYSA-N 0.000 description 1
- 102100028757 Chondroitin sulfate proteoglycan 4 Human genes 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000501458 Cultus Species 0.000 description 1
- ZMAODHOXRBLOQO-TZVKRXPSSA-N Cytochalasin A Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCCC(=O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 ZMAODHOXRBLOQO-TZVKRXPSSA-N 0.000 description 1
- LAJXCUNOQSHRJO-ZYGJITOWSA-N Cytochalasin E Chemical compound C([C@H]1[C@@H]2[C@@H]([C@]3(O[C@H]3[C@@H]3/C=C/C[C@H](C)C(=O)[C@](C)(O)/C=C/OC(=O)O[C@@]23C(=O)N1)C)C)C1=CC=CC=C1 LAJXCUNOQSHRJO-ZYGJITOWSA-N 0.000 description 1
- XJJSRPWDIFDUMY-UHFFFAOYSA-N Cytochalasin F Natural products CC1CCCC(O)C=CC(=O)OC23C(C=CC1)C4(O)OC4(C)C(C)C2C(Cc5ccccc5)NC3=O XJJSRPWDIFDUMY-UHFFFAOYSA-N 0.000 description 1
- YGKUXRWMCOUTAL-UHFFFAOYSA-N Cytochalasin G Natural products C12OC2(C)C(C)C2C(CC=3C4=CC=CC=C4NC=3)NC(=O)C22C1C=CCC(C)CC(=O)CCC2=O YGKUXRWMCOUTAL-UHFFFAOYSA-N 0.000 description 1
- UKQNIEMKORIOQM-UHFFFAOYSA-N Cytochalasin J Natural products N1C(=O)C2(C(C=CC(C)(O)CC(C)CC=C3)O)C3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 UKQNIEMKORIOQM-UHFFFAOYSA-N 0.000 description 1
- GGWOXIDGSYROGX-UHFFFAOYSA-N Cytochalasin L Natural products N1C(=O)C23OC(=O)C=CC(=O)C(OC(C)=O)C(C)=CC(C)CC=CC3C3OC3(C)C(C)C2C1CC1=CC=CC=C1 GGWOXIDGSYROGX-UHFFFAOYSA-N 0.000 description 1
- KXUADWPFUZOYLZ-UHFFFAOYSA-N Cytochalasin M Natural products N1C(=O)C23OC(=O)CCC(O)C(=O)C(C)=CC(C)CC=CC3C3OC3(C)C(C)C2C1CC1=CC=CC=C1 KXUADWPFUZOYLZ-UHFFFAOYSA-N 0.000 description 1
- WFSYATBEJTUDQA-UHFFFAOYSA-N Cytochalasin Npho Natural products N1C(=O)C23C(OC(C)=O)C=CC(C)(O)CC(C)CC=CC2C(O)C(C)=C(C)C3C1CC1=CC=CC=C1 WFSYATBEJTUDQA-UHFFFAOYSA-N 0.000 description 1
- UMHVFKLUODBPSC-UHFFFAOYSA-N Cytochalasin Opho Natural products N1C(=O)C23C(O)C=CC(C)(O)CC(C)CC=CC2C(O)C(C)=C(C)C3C1CC1=CC=CC=C1 UMHVFKLUODBPSC-UHFFFAOYSA-N 0.000 description 1
- AVASIWUXPVFFGK-UHFFFAOYSA-N Cytochalasin Ppho Natural products N1C(=O)C2(C(C=CC(C)(O)CC(C)CC=C3)OC(C)=O)C3C(O)C(O)(C)C(C)C2C1CC1=CC=CC=C1 AVASIWUXPVFFGK-UHFFFAOYSA-N 0.000 description 1
- AVASIWUXPVFFGK-WRERFMELSA-N Cytochalasin Ppho Chemical compound C([C@H]1[C@@H]2[C@@H]([C@]([C@@H](O)[C@H]\3[C@]2([C@@H](/C=C/[C@](C)(O)C[C@@H](C)C/C=C/3)OC(C)=O)C(=O)N1)(C)O)C)C1=CC=CC=C1 AVASIWUXPVFFGK-WRERFMELSA-N 0.000 description 1
- XHEQULXTQLICFN-UHFFFAOYSA-N Cytochalasin Q Natural products N1C(=O)C2(C(C=CC(C)(O)C(=O)C(C)CC=C3)OC(C)=O)C3C3OC3(C)C(C)C2C1CC1=CC=CC=C1 XHEQULXTQLICFN-UHFFFAOYSA-N 0.000 description 1
- IWNYMETYLRNJJP-UHFFFAOYSA-N Cytochalasin S Natural products CC1(O)C(C)C(O)C2C=CCC(C)CC(C)(O)C=CC(O)C2(C(N2)=O)C1C2CC1=CC=CC=C1 IWNYMETYLRNJJP-UHFFFAOYSA-N 0.000 description 1
- 102000008142 Cytochrome P-450 CYP1A1 Human genes 0.000 description 1
- 108010074918 Cytochrome P-450 CYP1A1 Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000010831 Cytoskeletal Proteins Human genes 0.000 description 1
- 108010037414 Cytoskeletal Proteins Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- GPCJCBIEJCXNKC-UHFFFAOYSA-N Desoxaphomin Natural products N1C(=O)C2(C(C=CC(O)CCCC(C)CC=C3)=O)C3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GPCJCBIEJCXNKC-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 102100033167 Elastin Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 description 1
- 101000817629 Homo sapiens Dymeclin Proteins 0.000 description 1
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 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 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 101000605401 Mus musculus Plasminogen Proteins 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- ZSRVBNXAPSQDFY-UHFFFAOYSA-N Mycobactin P Natural products OCC12CCC(C)=CC1OC1CC(O)C2(C)C11CO1 ZSRVBNXAPSQDFY-UHFFFAOYSA-N 0.000 description 1
- 108091005975 Myofilaments Proteins 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 241001111421 Pannus Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 208000020584 Polyploidy Diseases 0.000 description 1
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
- NNDRVGKCDJPTHD-UHFFFAOYSA-N Protophomin Natural products CC1=C(C)C(=O)C2C=CCC(C)CCCCC=CC(=O)C2(C(N2)=O)C1C2CC1=CC=CC=C1 NNDRVGKCDJPTHD-UHFFFAOYSA-N 0.000 description 1
- ILSZZTCTDIUCOJ-UHFFFAOYSA-N Proxiphomin Natural products N1C(=O)C2(C(C=CCCCCC(C)CC=C3)=O)C3C=C(C)C(C)C2C1CC1=CC=CC=C1 ILSZZTCTDIUCOJ-UHFFFAOYSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- BXFOFFBJRFZBQZ-QYWOHJEZSA-N T-2 toxin Chemical compound C([C@@]12[C@]3(C)[C@H](OC(C)=O)[C@@H](O)[C@H]1O[C@H]1[C@]3(COC(C)=O)C[C@@H](C(=C1)C)OC(=O)CC(C)C)O2 BXFOFFBJRFZBQZ-QYWOHJEZSA-N 0.000 description 1
- XZPCNXORIOQSOG-UHFFFAOYSA-N TAN-1030A Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(=NO)C(OC)C4(C)O1 XZPCNXORIOQSOG-UHFFFAOYSA-N 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- GSNOZLZNQMLSKJ-UHFFFAOYSA-N Trapidil Chemical compound CCN(CC)C1=CC(C)=NC2=NC=NN12 GSNOZLZNQMLSKJ-UHFFFAOYSA-N 0.000 description 1
- HNEGCRMUYSKRRR-UHFFFAOYSA-N Trichodermin Natural products CC(=O)OC1CC2OC3C=C(C)CCC3(C)C1(C)C21CO1 HNEGCRMUYSKRRR-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102000005937 Tropomyosin Human genes 0.000 description 1
- 108010030743 Tropomyosin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 206010072810 Vascular wall hypertrophy Diseases 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- 102000003970 Vinculin Human genes 0.000 description 1
- 108090000384 Vinculin Proteins 0.000 description 1
- YOSIWRQXBHJIKL-UHFFFAOYSA-N Zygosporin E Natural products N1C(=O)C2(C(C=CC(C)C(=O)C(C)CC=C3)OC(C)=O)C3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 YOSIWRQXBHJIKL-UHFFFAOYSA-N 0.000 description 1
- APXVRVLJIANRPI-UHFFFAOYSA-N Zygosporin F Natural products N1C(=O)C2(C(C=CC(C)(O)C(=O)C(C)CC=C3)OC(C)=O)C3C(OC(C)=O)C(=C)C(C)C2C1CC1=CC=CC=C1 APXVRVLJIANRPI-UHFFFAOYSA-N 0.000 description 1
- VFEKKHXLJKMKBO-UHFFFAOYSA-N Zygosporin G Natural products CC1CC=C/C2C=C(C)C(C)C3C(Cc4ccccc4)NC(=O)C23C(OC(=O)C)C=CC(C)(O)C1=O VFEKKHXLJKMKBO-UHFFFAOYSA-N 0.000 description 1
- GGWOXIDGSYROGX-XZRSCLCVSA-N [(1S,4E,7R,8Z,10S,12E,14S,15S,17R,18S,19S,20S)-20-benzyl-8,10,17,18-tetramethyl-3,6,22-trioxo-2,16-dioxa-21-azatetracyclo[12.8.0.01,19.015,17]docosa-4,8,12-trien-7-yl] acetate Chemical compound C[C@H]1[C@H]2[C@H](Cc3ccccc3)NC(=O)[C@]22OC(=O)\C=C\C(=O)[C@H](OC(C)=O)\C(C)=C/[C@@H](C)C\C=C\[C@H]2[C@@H]2O[C@]12C GGWOXIDGSYROGX-XZRSCLCVSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- DGOBMKYRQHEFGQ-UHFFFAOYSA-L acid green 5 Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 DGOBMKYRQHEFGQ-UHFFFAOYSA-L 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 description 1
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229930194440 aspochalasin Natural products 0.000 description 1
- BVKOTAZOMFVYMH-UHFFFAOYSA-N aspochalasin B Natural products C1=C(C)CCC(O)C(=O)C=CC(=O)C23C1C=C(C)C(C)C2C(CC(C)C)NC3=O BVKOTAZOMFVYMH-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 108091000084 calmodulin binding Proteins 0.000 description 1
- 102000028861 calmodulin binding Human genes 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229930191237 chaetoglobosin Natural products 0.000 description 1
- FPNAKNFLJIQADW-UHFFFAOYSA-N chaetoglobosin E Natural products O=C1CCC(O)C(=O)C(C)=CC(C)CC=CC2C(O)C(C)=C(C)C3C21C(=O)NC3CC1=CNC2=CC=CC=C12 FPNAKNFLJIQADW-UHFFFAOYSA-N 0.000 description 1
- FPNAKNFLJIQADW-CNYNBRRPSA-N chaetoglobosin E Chemical compound O=C1CC[C@H](O)C(=O)\C(C)=C\[C@@H](C)C\C=C\[C@H]2[C@H](O)C(C)=C(C)[C@@H]3[C@@]21C(=O)N[C@H]3CC1=CNC2=CC=CC=C12 FPNAKNFLJIQADW-CNYNBRRPSA-N 0.000 description 1
- KTFGDHPTDQFFRL-USMZZGTESA-N chaetoglobosin F Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)[C@@H]1[C@@H]([C@]2(O[C@H]22)C)C)C(=O)[C@@]11[C@H]2\C=C\C[C@H](C)\C=C(C)\C(=O)[C@@H](O)CCC1=O KTFGDHPTDQFFRL-USMZZGTESA-N 0.000 description 1
- XSYISNGSIFFBMR-YGCMOINNSA-N chaetoglobosin J Chemical compound N1C(=O)[C@@]2(C(/C=C/C(=O)[C@H](O)/C(C)=C/[C@@H](C)C/C=C/3)=O)[C@@H]\3C=C(C)[C@@H](C)[C@H]2[C@@H]1CC1=CNC2=CC=CC=C12 XSYISNGSIFFBMR-YGCMOINNSA-N 0.000 description 1
- LXPGDDICGFGPQK-UHFFFAOYSA-N chaetoglobosin O Natural products O=C1CCC(=O)C(O)C(C)=CC(C)CC=CC2C(O)C(C)=C(C)C3C21C(=O)NC3CC1=CNC2=CC=CC=C12 LXPGDDICGFGPQK-UHFFFAOYSA-N 0.000 description 1
- RIZAHVBYKWUPHQ-GNNSKLCBSA-N chaetoglobosin c Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)[C@@H]1[C@@H]([C@]2(O[C@H]22)C)C)C(=O)[C@@]11[C@H]2\C=C\C[C@H](C)\C=C(C)\C(=O)C(=O)CCC1=O RIZAHVBYKWUPHQ-GNNSKLCBSA-N 0.000 description 1
- FTBNYQWFSWKCKW-MRSLDMDQSA-N chaetoglobosin d Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)[C@@H]1[C@@H](C([C@H]2O)=C)C)C(=O)[C@@]11[C@H]2\C=C\C[C@H](C)\C=C(C)/[C@@H](O)C(=O)\C=C\C1=O FTBNYQWFSWKCKW-MRSLDMDQSA-N 0.000 description 1
- COZBDBUQXIMMKP-ZEUDSHDYSA-N chaetoglobosin g Chemical compound O=C1CCC(=O)C(=O)\C(C)=C/[C@@H](C)C\C=C\[C@H]2[C@H](O)C(C)=C(C)[C@@H]3[C@@]21C(=O)N[C@H]3CC1=CNC2=CC=CC=C12 COZBDBUQXIMMKP-ZEUDSHDYSA-N 0.000 description 1
- RSYKJHLWNMXRKZ-RVUXUPINSA-N chaetoglobosin k Chemical compound N([C@H]([C@@H]1[C@@H]([C@]2(O[C@H]22)C)CC)[C@@H](C)C=3C4=CC=CC=C4NC=3)C(=O)[C@@]11[C@H]2\C=C\C[C@H](C)\C=C(C)/[C@@H](O)C(=O)\C=C\C1=O RSYKJHLWNMXRKZ-RVUXUPINSA-N 0.000 description 1
- OUMWCYMRLMEZJH-ZZDWKPFVSA-N chaetoglobosin-A Natural products C[C@@H]1CC=C[C@H]2[C@@H]3O[C@]3(C)[C@H](C)[C@@H]4[C@@H](Cc5c[nH]c6ccccc56)NC(=O)[C@]24C(=O)C=CC(=O)[C@H](O)C(=C1)C OUMWCYMRLMEZJH-ZZDWKPFVSA-N 0.000 description 1
- DBZXOXDMOFFTPG-UHFFFAOYSA-N chaetoglobosin-F Natural products CC1CC=CC2C3OC3(C)C(C)C4C(Cc5c[nH]c6ccccc56)NC(=O)C24CCCC(O)C(=O)C(=C1)C DBZXOXDMOFFTPG-UHFFFAOYSA-N 0.000 description 1
- 229930187278 chaetoglobosins Natural products 0.000 description 1
- RIZAHVBYKWUPHQ-UHFFFAOYSA-N chaetoglobosins C Natural products C12OC2(C)C(C)C2C(CC=3C4=CC=CC=C4NC=3)NC(=O)C22C1C=CCC(C)C=C(C)C(=O)C(=O)CCC2=O RIZAHVBYKWUPHQ-UHFFFAOYSA-N 0.000 description 1
- COZBDBUQXIMMKP-UHFFFAOYSA-N chaetoglobosins G Natural products O=C1CCC(=O)C(=O)C(C)=CC(C)CC=CC2C(O)C(C)=C(C)C3C21C(=O)NC3CC1=CNC2=CC=CC=C12 COZBDBUQXIMMKP-UHFFFAOYSA-N 0.000 description 1
- CXWYFIYZAZBQGQ-IDLUQWPUSA-N chembl452486 Chemical compound C([C@H]1[C@@H]2[C@@H]([C@]3(O[C@H]3[C@@H]3/C=C/C[C@H](C)CCC[C@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)C)C)C1=CC=CC=C1 CXWYFIYZAZBQGQ-IDLUQWPUSA-N 0.000 description 1
- DMUBZPWTFAPROZ-CEAYGSLDSA-N chembl481643 Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@H]\3[C@]2([C@@H](/C=C/[C@@](C)(O)C(=O)[C@@H](C)C/C=C/3)O)C(=O)N1)=C)C)C1=CC=CC=C1 DMUBZPWTFAPROZ-CEAYGSLDSA-N 0.000 description 1
- ZSRVBNXAPSQDFY-OJVARPOJSA-N chembl504718 Chemical compound C([C@@]12[C@@]3([C@H](O)C[C@H]1O[C@@H]1C=C(CC[C@@]13CO)C)C)O2 ZSRVBNXAPSQDFY-OJVARPOJSA-N 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 239000002820 chemotaxin Substances 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 230000008576 chronic process Effects 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000011382 collagen catabolic process Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 210000003683 corneal stroma Anatomy 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000012297 crystallization seed Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- AZWOSJCABFILKS-UHFFFAOYSA-N cytochalasin K Natural products N1C(=O)C2(C(C=CC(=O)C(OC(C)=O)C(C)=CC(C)CC=C3)=O)C3C3OC3(C)C(C)C2C1CC1=CC=CC=C1 AZWOSJCABFILKS-UHFFFAOYSA-N 0.000 description 1
- KPIFCQLJNVZJNN-UHFFFAOYSA-N cytochalasin O Natural products N1C(=O)C2(C(C=CC(C)(O)C(=O)C(C)CC=C3)OC(C)=O)C3C(O)C(O)(C)C(C)C2C1CC1=CC=CC=C1 KPIFCQLJNVZJNN-UHFFFAOYSA-N 0.000 description 1
- KHJAUVJHBOZECO-LHTVRZEWSA-N cytochalasin R Natural products C[C@H]1C[C@H]2O[C@@H]2[C@H]3[C@@H]4O[C@]4(C)[C@@H](C)[C@H]5[C@H](Cc6ccccc6)NC(=O)[C@@]35[C@H](OC(=O)C)C=C[C@@](C)(O)C1=O KHJAUVJHBOZECO-LHTVRZEWSA-N 0.000 description 1
- UKQNIEMKORIOQM-GRIAELCMSA-N cytochalasin j Chemical compound C([C@H]1[C@@H]2[C@@H](C(C(O)[C@H]\3C2([C@@H](/C=C/C(C)(O)CC(C)C/C=C/3)O)C(=O)N1)=C)C)C1=CC=CC=C1 UKQNIEMKORIOQM-GRIAELCMSA-N 0.000 description 1
- WFSYATBEJTUDQA-WQNUPBJZSA-N cytochalasin n Chemical compound C([C@H]1[C@@H]2C(C)=C(C)[C@@H](O)[C@@H]3/C=C/C[C@@H](C[C@@](C)(O)/C=C/[C@@H](OC(C)=O)[C@]32C(=O)N1)C)C1=CC=CC=C1 WFSYATBEJTUDQA-WQNUPBJZSA-N 0.000 description 1
- XHEQULXTQLICFN-QDNKZWAGSA-N cytochalasin q Chemical compound C([C@H]1[C@@H]2[C@@H]([C@]3(O[C@H]3[C@H]\3[C@]2([C@@H](/C=C/[C@@](C)(O)C(=O)[C@@H](C)C/C=C/3)OC(C)=O)C(=O)N1)C)C)C1=CC=CC=C1 XHEQULXTQLICFN-QDNKZWAGSA-N 0.000 description 1
- IWNYMETYLRNJJP-RCKNNXTOSA-N cytochalasin s Chemical compound C([C@H]1[C@H]2[C@]3(C(N1)=O)[C@H](O)/C=C/[C@](C)(O)C[C@@H](C)C/C=C/[C@H]3[C@H](O)[C@@H]([C@@]2(C)O)C)C1=CC=CC=C1 IWNYMETYLRNJJP-RCKNNXTOSA-N 0.000 description 1
- DZPQCIIHBSGJDD-QZPZKAQASA-N cytochalasin-E Natural products C[C@@H]1CC=C[C@@H]2[C@H](O)[C@@H](C)C(=C3[C@H](Cc4ccccc4)NC(=O)[C@@]23OC(=O)OC=C[C@](C)(O)C1=O)C DZPQCIIHBSGJDD-QZPZKAQASA-N 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000001516 effect on protein Effects 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 108010036236 extracellular matrix receptor Proteins 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 125000006302 indol-3-yl methyl group Chemical group [H]N1C([H])=C(C2=C([H])C([H])=C([H])C([H])=C12)C([H])([H])* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000008069 intimal proliferation Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- CVRCKYSJULOPFH-UHFFFAOYSA-N isocytochalasin N Natural products N1C(=O)C23C(OC(C)=O)C=CC(C)(O)C(=O)C(C)CC=CC2C(O)C2(C)OC2(C)C3C1CC1=CC=CC=C1 CVRCKYSJULOPFH-UHFFFAOYSA-N 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229940051132 light green sf yellowish Drugs 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 210000003975 mesenteric artery Anatomy 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- SBVVUEPVKSOHHY-UHFFFAOYSA-N n,n-dimethyl-1-phenoxyethanamine Chemical compound CN(C)C(C)OC1=CC=CC=C1 SBVVUEPVKSOHHY-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
- 229960005366 nilvadipine Drugs 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000009543 pathological alteration Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 108010059929 phospholamban Proteins 0.000 description 1
- 102000005681 phospholamban Human genes 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000013310 pig model Methods 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920002959 polymer blend Polymers 0.000 description 1
- 210000001850 polyploid cell Anatomy 0.000 description 1
- 230000004978 positive regulation of smooth muscle cell proliferation Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
- 238000012342 propidium iodide staining Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000003881 protein kinase C inhibitor Substances 0.000 description 1
- NNDRVGKCDJPTHD-NMYAVHRMSA-N protophomin Chemical compound CC1=C(C)C(=O)C2\C=C\CC(C)CCCC\C=C/C(=O)C2(C(N2)=O)C1C2CC1=CC=CC=C1 NNDRVGKCDJPTHD-NMYAVHRMSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- OSJFVOAURBIGTC-SFDUFSHASA-N rk-286c Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@@H]1C[C@H](O)[C@H](OC)[C@@]4(C)O1 OSJFVOAURBIGTC-SFDUFSHASA-N 0.000 description 1
- 210000003935 rough endoplasmic reticulum Anatomy 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 230000024053 secondary metabolic process Effects 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960002385 streptomycin sulfate Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- ZXQPCJUWQQAWKY-UHFFFAOYSA-N tan 999 Chemical compound C12=C3N4C5=CC(OC)=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(=NC)C(OC)C4(C)O1 ZXQPCJUWQQAWKY-UHFFFAOYSA-N 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229960001594 tiletamine hydrochloride Drugs 0.000 description 1
- 238000002287 time-lapse microscopy Methods 0.000 description 1
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical class OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229960000363 trapidil Drugs 0.000 description 1
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical compound BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 1
- HNEGCRMUYSKRRR-IKIFYQGPSA-N trichodermin Chemical compound C([C@@]12[C@@]3(C)[C@@]4(C)CCC(C)=C[C@H]4O[C@@H]1C[C@H]3OC(=O)C)O2 HNEGCRMUYSKRRR-IKIFYQGPSA-N 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 230000007995 vascular wound healing Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- FAWYVFPVBYQAHD-UHFFFAOYSA-N zygosporin D Natural products N1C(=O)C2(C(C=CC(C)(O)C(=O)C(C)CC=C3)O)C3C(=O)C(C)C(C)C2C1CC1=CC=CC=C1 FAWYVFPVBYQAHD-UHFFFAOYSA-N 0.000 description 1
- APXVRVLJIANRPI-VUOSUOSOSA-N zygosporin f Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](OC(C)=O)[C@H]\3[C@]2([C@@H](/C=C/[C@@](C)(O)C(=O)[C@@H](C)C/C=C/3)OC(C)=O)C(=O)N1)=C)C)C1=CC=CC=C1 APXVRVLJIANRPI-VUOSUOSOSA-N 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US6245193A | 1993-05-13 | 1993-05-13 | |
US08/062,451 | 1993-05-13 | ||
CA002162587A CA2162587C (fr) | 1993-05-13 | 1994-05-12 | Inhibiteur therapeutique des cellules vasculaires du muscle lisse |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002162587A Division CA2162587C (fr) | 1993-05-13 | 1994-05-12 | Inhibiteur therapeutique des cellules vasculaires du muscle lisse |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2455985A1 true CA2455985A1 (fr) | 1994-11-24 |
Family
ID=32094343
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002455985A Abandoned CA2455985A1 (fr) | 1993-05-13 | 1994-05-12 | Inhibiteur therapeutique des cellules vasculaires du muscle lisse |
Country Status (1)
Country | Link |
---|---|
CA (1) | CA2455985A1 (fr) |
-
1994
- 1994-05-12 CA CA002455985A patent/CA2455985A1/fr not_active Abandoned
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2162587C (fr) | Inhibiteur therapeutique des cellules vasculaires du muscle lisse | |
US5545569A (en) | Prevention and treatment of pathologies associated with abnormally proliferative smooth muscle cells | |
US6268390B1 (en) | Therapeutic inhibitor of vascular smooth muscle cells | |
US5770609A (en) | Prevention and treatment of cardiovascular pathologies | |
US5595722A (en) | Method for identifying an agent which increases TGF-beta levels | |
US6171609B1 (en) | Therapeutic inhibitor of vascular smooth muscle cells | |
US6197789B1 (en) | Prevention and treatment of cardiovascular pathologies with tamoxifen analogues | |
US6262079B1 (en) | Prevention and treatment of cardiovascular pathologies | |
US6720350B2 (en) | Therapeutic inhibitor of vascular smooth muscle cells | |
US20060029986A1 (en) | Prevention and treatment of cardiovascular pathologies | |
EP0681475B1 (fr) | Inhibiteur therapeutique de cellules de muscles vasculaires lisses | |
US20040219223A1 (en) | Therapeutic inhibitor of vascular smooth muscle cells | |
CA2455985A1 (fr) | Inhibiteur therapeutique des cellules vasculaires du muscle lisse |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
FZDE | Dead |