AU2016357720A1 - Biomarker of polycystic kidney disease and uses thereof - Google Patents

Info

Publication number

AU2016357720A1

AU2016357720A1 AU2016357720A AU2016357720A AU2016357720A1 AU 2016357720 A1 AU2016357720 A1 AU 2016357720A1 AU 2016357720 A AU2016357720 A AU 2016357720A AU 2016357720 A AU2016357720 A AU 2016357720A AU 2016357720 A1 AU2016357720 A1 AU 2016357720A1

Authority

AU

Australia

Prior art keywords

leu

glu

gly

ala

lys

Prior art date

2015-11-18

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

• Espacenet
• Global Dossier
• Discuss

• 208000030761 polycystic kidney disease Diseases 0.000 title claims abstract description 369
• 239000000090 biomarker Substances 0.000 title claims description 6
• 238000000034 method Methods 0.000 claims abstract description 176
• 238000011282 treatment Methods 0.000 claims abstract description 91
• 102100032859 Protein AMBP Human genes 0.000 claims abstract description 48
• 101000797623 Homo sapiens Protein AMBP Proteins 0.000 claims abstract description 43
• 238000012544 monitoring process Methods 0.000 claims abstract description 9
• 108090000623 proteins and genes Proteins 0.000 claims description 112
• 102000004169 proteins and genes Human genes 0.000 claims description 109
• 210000002700 urine Anatomy 0.000 claims description 64
• 210000003734 kidney Anatomy 0.000 claims description 63
• 241000282414 Homo sapiens Species 0.000 claims description 39
• 239000013060 biological fluid Substances 0.000 claims description 38
• DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims description 31
• 210000005084 renal tissue Anatomy 0.000 claims description 28
• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 claims description 25
• 229940125921 glucosylceramide synthase inhibitor Drugs 0.000 claims description 24
• 239000004305 biphenyl Substances 0.000 claims description 23
• -1 quinuclidin-3-yl Chemical group 0.000 claims description 23
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 22
• 102000044956 Ceramide glucosyltransferases Human genes 0.000 claims description 21
• 108091000114 ceramide glucosyltransferase Proteins 0.000 claims description 21
• 239000002875 cyclin dependent kinase inhibitor Substances 0.000 claims description 20
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 20
• BTIHMVBBUGXLCJ-OAHLLOKOSA-N seliciclib Chemical group C=12N=CN(C(C)C)C2=NC(N[C@@H](CO)CC)=NC=1NCC1=CC=CC=C1 BTIHMVBBUGXLCJ-OAHLLOKOSA-N 0.000 claims description 17
• 239000003112 inhibitor Substances 0.000 claims description 15
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 13
• 230000003068 static effect Effects 0.000 claims description 13
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims description 13
• 238000003384 imaging method Methods 0.000 claims description 12
• RVNGOAZBZQNZSJ-UHFFFAOYSA-N 4-fluoro-1-[4-[4-(2-methoxyethoxy)phenyl]pyrimidin-2-yl]-n-(3-methyl-1-azabicyclo[2.2.2]octan-3-yl)piperidine-4-carboxamide Chemical compound C1=CC(OCCOC)=CC=C1C1=CC=NC(N2CCC(F)(CC2)C(=O)NC2(C)C3CCN(CC3)C2)=N1 RVNGOAZBZQNZSJ-UHFFFAOYSA-N 0.000 claims description 11
• XQHFDBAIOCBLAT-UHFFFAOYSA-N 4-fluoro-1-[4-[4-(2-methoxyethoxymethyl)phenyl]pyrimidin-2-yl]-N-(3-methyl-1-azabicyclo[2.2.2]octan-3-yl)piperidine-4-carboxamide Chemical compound COCCOCc1ccc(cc1)-c1ccnc(n1)N1CCC(F)(CC1)C(=O)NC1(C)CN2CCC1CC2 XQHFDBAIOCBLAT-UHFFFAOYSA-N 0.000 claims description 11
• BHQKXEPIAXCKKU-UHFFFAOYSA-N 4-fluoro-1-[5-fluoro-4-[4-(2-methoxyethoxymethyl)phenyl]pyrimidin-2-yl]-n-(4-methyl-1-azabicyclo[3.2.2]nonan-4-yl)piperidine-4-carboxamide Chemical compound C1=CC(COCCOC)=CC=C1C1=NC(N2CCC(F)(CC2)C(=O)NC2(C)C3CCN(CC3)CC2)=NC=C1F BHQKXEPIAXCKKU-UHFFFAOYSA-N 0.000 claims description 11
• NMAHPRBPCRWREJ-UHFFFAOYSA-N 4-fluoro-1-[4-[4-(2-methoxyethoxy)phenyl]pyrimidin-2-yl]-N-(4-methyl-1-azabicyclo[3.2.2]nonan-4-yl)piperidine-4-carboxamide Chemical compound FC1(CCN(CC1)C1=NC=CC(=N1)C1=CC=C(C=C1)OCCOC)C(=O)NC1(CCN2CCC1CC2)C NMAHPRBPCRWREJ-UHFFFAOYSA-N 0.000 claims description 10
• KMMSLXMCZJHSJG-UHFFFAOYSA-N 4-fluoro-1-[4-[4-(methoxymethyl)phenyl]pyrimidin-2-yl]-n-(3-methyl-1-azabicyclo[2.2.2]octan-3-yl)piperidine-4-carboxamide Chemical compound C1=CC(COC)=CC=C1C1=CC=NC(N2CCC(F)(CC2)C(=O)NC2(C)C3CCN(CC3)C2)=N1 KMMSLXMCZJHSJG-UHFFFAOYSA-N 0.000 claims description 8
• DXGMIVPGWLGGPE-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-3-yl)-4-fluoro-1-[4-[4-(2-fluoroethoxy)phenyl]pyrimidin-2-yl]piperidine-4-carboxamide Chemical compound C1=CC(OCCF)=CC=C1C1=CC=NC(N2CCC(F)(CC2)C(=O)NC2C3CCN(CC3)C2)=N1 DXGMIVPGWLGGPE-UHFFFAOYSA-N 0.000 claims description 8
• 239000012474 protein marker Substances 0.000 claims description 6
• KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 claims 18
• 108010050848 glycylleucine Proteins 0.000 claims 16
• 108010054155 lysyllysine Proteins 0.000 claims 14
• YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 claims 12
• SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 claims 11
• 108010034529 leucyl-lysine Proteins 0.000 claims 11
• 108010026333 seryl-proline Proteins 0.000 claims 11
• 108010055341 glutamyl-glutamic acid Proteins 0.000 claims 10
• 108010005233 alanylglutamic acid Proteins 0.000 claims 9
• 108010057821 leucylproline Proteins 0.000 claims 9
• 108010009298 lysylglutamic acid Proteins 0.000 claims 9
• 108010029020 prolylglycine Proteins 0.000 claims 9
• 108010056582 methionylglutamic acid Proteins 0.000 claims 8
• AIGROOHQXCACHL-WDSKDSINSA-N Glu-Gly-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(O)=O AIGROOHQXCACHL-WDSKDSINSA-N 0.000 claims 7
• HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 claims 7
• KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 claims 7
• 108010062796 arginyllysine Proteins 0.000 claims 7
• 108010003700 lysyl aspartic acid Proteins 0.000 claims 7
• 108010061238 threonyl-glycine Proteins 0.000 claims 7
• 108010090461 DFG peptide Proteins 0.000 claims 6
• MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 claims 6
• GGEJHJIXRBTJPD-BYPYZUCNSA-N Gly-Asn-Gly Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O GGEJHJIXRBTJPD-BYPYZUCNSA-N 0.000 claims 6
• 241000880493 Leptailurus serval Species 0.000 claims 6
• 108010079005 RDV peptide Proteins 0.000 claims 6
• COYSIHFOCOMGCF-WPRPVWTQSA-N Val-Arg-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-WPRPVWTQSA-N 0.000 claims 6
• COYSIHFOCOMGCF-UHFFFAOYSA-N Val-Arg-Gly Natural products CC(C)C(N)C(=O)NC(C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-UHFFFAOYSA-N 0.000 claims 6
• 108010047495 alanylglycine Proteins 0.000 claims 6
• 108010091092 arginyl-glycyl-proline Proteins 0.000 claims 6
• 108010069205 aspartyl-phenylalanine Proteins 0.000 claims 6
• 108010049041 glutamylalanine Proteins 0.000 claims 6
• 108010027338 isoleucylcysteine Proteins 0.000 claims 6
• 108010064235 lysylglycine Proteins 0.000 claims 6
• 108010004914 prolylarginine Proteins 0.000 claims 6
• 108010090894 prolylleucine Proteins 0.000 claims 6
• 108010073969 valyllysine Proteins 0.000 claims 6
• RZZMZYZXNJRPOJ-BJDJZHNGSA-N Ala-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](C)N RZZMZYZXNJRPOJ-BJDJZHNGSA-N 0.000 claims 5
• RUXQNKVQSKOOBS-JURCDPSOSA-N Ala-Phe-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RUXQNKVQSKOOBS-JURCDPSOSA-N 0.000 claims 5
• CNKAZIGBGQIHLL-GUBZILKMSA-N Asp-Arg-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N CNKAZIGBGQIHLL-GUBZILKMSA-N 0.000 claims 5
• FTIJVMLAGRAYMJ-MNXVOIDGSA-N Gln-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(N)=O FTIJVMLAGRAYMJ-MNXVOIDGSA-N 0.000 claims 5
• XFAUJGNLHIGXET-AVGNSLFASA-N Gln-Leu-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XFAUJGNLHIGXET-AVGNSLFASA-N 0.000 claims 5
• ZHNHJYYFCGUZNQ-KBIXCLLPSA-N Glu-Ile-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(O)=O ZHNHJYYFCGUZNQ-KBIXCLLPSA-N 0.000 claims 5
• JWLWNCVBBSBCEM-NKIYYHGXSA-N His-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CN=CN1)N)O JWLWNCVBBSBCEM-NKIYYHGXSA-N 0.000 claims 5
• FZWVCYCYWCLQDH-NHCYSSNCSA-N Ile-Leu-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)O)N FZWVCYCYWCLQDH-NHCYSSNCSA-N 0.000 claims 5
• UHNQRAFSEBGZFZ-YESZJQIVSA-N Leu-Phe-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N UHNQRAFSEBGZFZ-YESZJQIVSA-N 0.000 claims 5
• PRSBSVAVOQOAMI-BJDJZHNGSA-N Lys-Ile-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN PRSBSVAVOQOAMI-BJDJZHNGSA-N 0.000 claims 5
• JIWJRKNYLSHONY-KKUMJFAQSA-N Pro-Phe-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O JIWJRKNYLSHONY-KKUMJFAQSA-N 0.000 claims 5
• MGJLBZFUXUGMML-VOAKCMCISA-N Thr-Lys-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MGJLBZFUXUGMML-VOAKCMCISA-N 0.000 claims 5
• BSCBBPKDVOZICB-KKUMJFAQSA-N Tyr-Leu-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O BSCBBPKDVOZICB-KKUMJFAQSA-N 0.000 claims 5
• 108010044940 alanylglutamine Proteins 0.000 claims 5
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• 108010003137 tyrosyltyrosine Proteins 0.000 claims 5
• AXFMEGAFCUULFV-BLFANLJRSA-N (2s)-2-[[(2s)-1-[(2s,3r)-2-amino-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]pentanedioic acid Chemical compound CC[C@@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AXFMEGAFCUULFV-BLFANLJRSA-N 0.000 claims 4
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• 108010087924 alanylproline Proteins 0.000 claims 4
• 108010013835 arginine glutamate Proteins 0.000 claims 4
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• 108010077245 asparaginyl-proline Proteins 0.000 claims 4
• 108010078144 glutaminyl-glycine Proteins 0.000 claims 4
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