CA2915250A1 - Cell stabilization - Google Patents
Cell stabilization Download PDFInfo
- Publication number
- CA2915250A1 CA2915250A1 CA2915250A CA2915250A CA2915250A1 CA 2915250 A1 CA2915250 A1 CA 2915250A1 CA 2915250 A CA2915250 A CA 2915250A CA 2915250 A CA2915250 A CA 2915250A CA 2915250 A1 CA2915250 A1 CA 2915250A1
- Authority
- CA
- Canada
- Prior art keywords
- inhibitor
- composition
- cell
- formulation
- apoptosis
- 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
- 230000006641 stabilisation Effects 0.000 title abstract description 9
- 238000011105 stabilization Methods 0.000 title abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 326
- 238000009472 formulation Methods 0.000 claims abstract description 221
- 230000018044 dehydration Effects 0.000 claims abstract description 89
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 89
- 238000003860 storage Methods 0.000 claims abstract description 83
- 238000000034 method Methods 0.000 claims abstract description 71
- 210000004027 cell Anatomy 0.000 claims description 257
- 229940088872 Apoptosis inhibitor Drugs 0.000 claims description 187
- 239000000158 apoptosis inhibitor Substances 0.000 claims description 187
- 239000003112 inhibitor Substances 0.000 claims description 121
- 108090000623 proteins and genes Proteins 0.000 claims description 54
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims description 42
- 102100030013 Endoribonuclease Human genes 0.000 claims description 40
- LCOIAYJMPKXARU-VAWYXSNFSA-N salubrinal Chemical compound C=1C=CC2=CC=CN=C2C=1NC(=S)NC(C(Cl)(Cl)Cl)NC(=O)\C=C\C1=CC=CC=C1 LCOIAYJMPKXARU-VAWYXSNFSA-N 0.000 claims description 39
- 108010079785 calpain inhibitors Proteins 0.000 claims description 38
- 239000000411 inducer Substances 0.000 claims description 37
- 102000004169 proteins and genes Human genes 0.000 claims description 37
- 229940121926 Calpain inhibitor Drugs 0.000 claims description 34
- 102100035037 Calpastatin Human genes 0.000 claims description 34
- 108010044208 calpastatin Proteins 0.000 claims description 34
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 34
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 34
- 239000012825 JNK inhibitor Substances 0.000 claims description 31
- 229940118135 JNK inhibitor Drugs 0.000 claims description 27
- 229940124647 MEK inhibitor Drugs 0.000 claims description 27
- 230000004083 survival effect Effects 0.000 claims description 24
- 108010006519 Molecular Chaperones Proteins 0.000 claims description 21
- 150000001413 amino acids Chemical class 0.000 claims description 21
- 230000004900 autophagic degradation Effects 0.000 claims description 21
- 108010027775 interleukin-1beta-converting enzyme inhibitor Proteins 0.000 claims description 21
- 229940122696 MAP kinase inhibitor Drugs 0.000 claims description 20
- 230000037361 pathway Effects 0.000 claims description 19
- -1 2-(2-chloro-iodophenylamino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 239000003381 stabilizer Substances 0.000 claims description 16
- 229940127254 ASK1 inhibitor Drugs 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 230000002441 reversible effect Effects 0.000 claims description 13
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 claims description 13
- 229940102566 valproate Drugs 0.000 claims description 13
- 108010076667 Caspases Proteins 0.000 claims description 12
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- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims description 11
- 229920003169 water-soluble polymer Polymers 0.000 claims description 11
- SVFLBLCWKKQKDW-UHFFFAOYSA-N 2-(3,4-dihydroxyphenyl)-2-oxoethyl thiocyanate Chemical group OC1=CC=C(C(=O)CSC#N)C=C1O SVFLBLCWKKQKDW-UHFFFAOYSA-N 0.000 claims description 10
- 101100452784 Caenorhabditis elegans ire-1 gene Proteins 0.000 claims description 10
- TUVCWJQQGGETHL-UHFFFAOYSA-N PI-103 Chemical compound OC1=CC=CC(C=2N=C3C4=CC=CN=C4OC3=C(N3CCOCC3)N=2)=C1 TUVCWJQQGGETHL-UHFFFAOYSA-N 0.000 claims description 10
- JCRSHQCFRMCMOC-GSDHBNRESA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-4-fluoro-1-(4-hydroxyphenyl)-3-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)CF)C(=O)OCC1=CC=CC=C1 JCRSHQCFRMCMOC-GSDHBNRESA-N 0.000 claims description 10
- QRYRORQUOLYVBU-VBKZILBWSA-N carnosic acid Chemical group CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 claims description 10
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- MDZCSIDIPDZWKL-UHFFFAOYSA-N CHIR-98014 Chemical group C1=C([N+]([O-])=O)C(N)=NC(NCCNC=2N=C(C(=CN=2)N2C=NC=C2)C=2C(=CC(Cl)=CC=2)Cl)=C1 MDZCSIDIPDZWKL-UHFFFAOYSA-N 0.000 claims description 8
- CZQHHVNHHHRRDU-UHFFFAOYSA-N LY294002 Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1C1=CC=CC=C1 CZQHHVNHHHRRDU-UHFFFAOYSA-N 0.000 claims description 8
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 8
- 229910052744 lithium Inorganic materials 0.000 claims description 8
- 239000006174 pH buffer Substances 0.000 claims description 8
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- SJVQHLPISAIATJ-ZDUSSCGKSA-N 8-chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]-1-isoquinolinone Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=CC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1 SJVQHLPISAIATJ-ZDUSSCGKSA-N 0.000 claims description 7
- ACPOUJIDANTYHO-UHFFFAOYSA-N anthra[1,9-cd]pyrazol-6(2H)-one Chemical group C1=CC(C(=O)C=2C3=CC=CC=2)=C2C3=NNC2=C1 ACPOUJIDANTYHO-UHFFFAOYSA-N 0.000 claims description 7
- 239000002738 chelating agent Substances 0.000 claims description 7
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 7
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- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 7
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- QFWCYNPOPKQOKV-UHFFFAOYSA-N 2-(2-amino-3-methoxyphenyl)chromen-4-one Chemical compound COC1=CC=CC(C=2OC3=CC=CC=C3C(=O)C=2)=C1N QFWCYNPOPKQOKV-UHFFFAOYSA-N 0.000 claims description 6
- HJGMCDHQPXTGAV-UHFFFAOYSA-N 2-(4-chlorophenoxy)-n-[4-[[2-(4-chlorophenoxy)acetyl]amino]cyclohexyl]acetamide Chemical compound C1=CC(Cl)=CC=C1OCC(=O)NC1CCC(NC(=O)COC=2C=CC(Cl)=CC=2)CC1 HJGMCDHQPXTGAV-UHFFFAOYSA-N 0.000 claims description 6
- XTKLTGBKIDQGQL-UHFFFAOYSA-N 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid Chemical compound CC1=NC2=C(C(O)=O)C=C(N3CCOCC3)C=C2N1CC1=CC=CC(C(F)(F)F)=C1C XTKLTGBKIDQGQL-UHFFFAOYSA-N 0.000 claims description 6
- BGIYKDUASORTBB-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-2-(4-nitrophenyl)-1H-imidazol-5-yl]pyridine Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NC(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N1 BGIYKDUASORTBB-UHFFFAOYSA-N 0.000 claims description 6
- NARMJPIBAXVUIE-UHFFFAOYSA-N 5-[2-tert-butyl-4-(4-fluorophenyl)-1h-imidazol-5-yl]-3-(2,2-dimethylpropyl)imidazo[4,5-b]pyridin-2-amine;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.N1=C2N(CC(C)(C)C)C(N)=NC2=CC=C1C=1N=C(C(C)(C)C)NC=1C1=CC=C(F)C=C1 NARMJPIBAXVUIE-UHFFFAOYSA-N 0.000 claims description 6
- FYSRKRZDBHOFAY-UHFFFAOYSA-N 6-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)-3-pyridinecarboxamide Chemical compound FC=1C=CC=C(F)C=1N(C(=O)N)C(N=1)=CC=C(C(N)=O)C=1C1=CC=C(F)C=C1F FYSRKRZDBHOFAY-UHFFFAOYSA-N 0.000 claims description 6
- JAMULYFATHSZJM-UHFFFAOYSA-N 8-(4-dibenzothiophenyl)-2-(4-morpholinyl)-1-benzopyran-4-one Chemical compound O1C2=C(C=3C=4SC5=CC=CC=C5C=4C=CC=3)C=CC=C2C(=O)C=C1N1CCOCC1 JAMULYFATHSZJM-UHFFFAOYSA-N 0.000 claims description 6
- CPRAGQJXBLMUEL-UHFFFAOYSA-N 9-(1-anilinoethyl)-7-methyl-2-(4-morpholinyl)-4-pyrido[1,2-a]pyrimidinone Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=C1 CPRAGQJXBLMUEL-UHFFFAOYSA-N 0.000 claims description 6
- SJDDOCKBXFJEJB-MOKWFATOSA-N Belnacasan Chemical compound CCO[C@@H]1OC(=O)C[C@@H]1NC(=O)[C@H]1N(C(=O)[C@@H](NC(=O)C=2C=C(Cl)C(N)=CC=2)C(C)(C)C)CCC1 SJDDOCKBXFJEJB-MOKWFATOSA-N 0.000 claims description 6
- PRWSIEBRGXYXAJ-UHFFFAOYSA-N GSK2656157 Chemical compound CC1=CC=CC(CC(=O)N2C3=C(C(=C(C=4C5=C(N)N=CN=C5N(C)C=4)C=C3)F)CC2)=N1 PRWSIEBRGXYXAJ-UHFFFAOYSA-N 0.000 claims description 6
- FCKJZIRDZMVDEM-UHFFFAOYSA-N N-(7,8-dimethoxy-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene)pyridine-3-carboxamide Chemical compound COC1=C(C2=NC(=NC(=O)C3=CN=CC=C3)N4CCNC4=C2C=C1)OC FCKJZIRDZMVDEM-UHFFFAOYSA-N 0.000 claims description 6
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- HEKAIDKUDLCBRU-UHFFFAOYSA-N N-[4-[2-ethyl-4-(3-methylphenyl)-5-thiazolyl]-2-pyridinyl]benzamide Chemical compound S1C(CC)=NC(C=2C=C(C)C=CC=2)=C1C(C=1)=CC=NC=1NC(=O)C1=CC=CC=C1 HEKAIDKUDLCBRU-UHFFFAOYSA-N 0.000 claims description 6
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
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| CN106687580A (zh) * | 2014-06-10 | 2017-05-17 | 生物马特里卡公司 | 在环境温度下稳定血液样品中的代谢活性细胞 |
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| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| US9376709B2 (en) | 2010-07-26 | 2016-06-28 | Biomatrica, Inc. | Compositions for stabilizing DNA and RNA in blood and other biological samples during shipping and storage at ambient temperatures |
| WO2012018639A2 (en) | 2010-07-26 | 2012-02-09 | Biomatrica, Inc. | Compositions for stabilizing dna, rna and proteins in saliva and other biological samples during shipping and storage at ambient temperatures |
| AR084824A1 (es) | 2011-01-10 | 2013-06-26 | Intellikine Inc | Procesos para preparar isoquinolinonas y formas solidas de isoquinolinonas |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| HRP20181367T4 (hr) | 2012-11-01 | 2021-11-26 | Infinity Pharmaceuticals, Inc. | Liječenje raka korištenjem modulatora izoforme pi3 kinaze |
| WO2014100755A2 (en) | 2012-12-20 | 2014-06-26 | Biomatrica, Inc. | Formulations and methods for stabilizing pcr reagents |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| EP3154338B1 (en) | 2014-06-10 | 2020-01-29 | Biomatrica, INC. | Stabilization of thrombocytes at ambient temperatures |
| EP3347448B1 (en) | 2015-09-09 | 2020-07-08 | Drawbridge Health, Inc. | Methods for sample collection, stabilization and preservation |
| KR102787387B1 (ko) | 2015-12-08 | 2025-03-26 | 바이오매트리카 인코포레이티드 | 적혈구 침강 속도의 감소 |
| JPWO2017130756A1 (ja) * | 2016-01-25 | 2018-11-29 | 学校法人慶應義塾 | 小胞体ストレスを標的とする椎間板変性症に対する治療薬 |
| KR101662975B1 (ko) * | 2016-02-15 | 2016-10-06 | 서울대학교산학협력단 | 간암 치료 또는 예방용 조성물 |
| CN109311930B (zh) * | 2016-03-31 | 2023-02-24 | 伯克利之光生命科技公司 | 核酸稳定试剂、试剂盒及其使用方法 |
| CA3028718A1 (en) | 2016-06-24 | 2017-12-28 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| US20190388426A1 (en) | 2017-01-30 | 2019-12-26 | Université de Liège | Perk and ire-1a inhibitors against neurodevelopmental disorders |
| CN106963769B (zh) * | 2017-03-03 | 2019-10-25 | 深圳大学 | 含pi3k抑制剂和perk抑制剂的药物组合物及其应用 |
| GB201804227D0 (en) * | 2018-03-16 | 2018-05-02 | Univ Warwick | Cryopreserving compositions |
| WO2021041399A1 (en) * | 2019-08-29 | 2021-03-04 | Board Of Regents, The University Of Texas System | Cell cryopreservation medium |
| CN111418579B (zh) * | 2020-04-13 | 2021-05-18 | 广东华夏健康生命科学有限公司 | 一种脂肪组织的保存方法、脂肪组织的保存液及其制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106687580A (zh) * | 2014-06-10 | 2017-05-17 | 生物马特里卡公司 | 在环境温度下稳定血液样品中的代谢活性细胞 |
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| JP2016522221A (ja) | 2016-07-28 |
| US20160135446A1 (en) | 2016-05-19 |
| CN105491883B (zh) | 2018-11-02 |
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| JP6604942B2 (ja) | 2019-11-13 |
| CN105491883A (zh) | 2016-04-13 |
| EP3007556A4 (en) | 2017-03-08 |
| WO2015002729A3 (en) | 2015-05-07 |
| EP3007556A2 (en) | 2016-04-20 |
| US20180184644A1 (en) | 2018-07-05 |
| EP3632208A1 (en) | 2020-04-08 |
| EP3007556B1 (en) | 2020-05-20 |
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