CN109985228A - 拟钙剂及其使用方法 - Google Patents
拟钙剂及其使用方法 Download PDFInfo
- Publication number
- CN109985228A CN109985228A CN201910103503.4A CN201910103503A CN109985228A CN 109985228 A CN109985228 A CN 109985228A CN 201910103503 A CN201910103503 A CN 201910103503A CN 109985228 A CN109985228 A CN 109985228A
- Authority
- CN
- China
- Prior art keywords
- sensipar
- seq
- pth
- dosage
- compound
- 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.)
- Pending
Links
- VDHAWDNDOKGFTD-MRXNPFEDSA-N cinacalcet Chemical compound N([C@H](C)C=1C2=CC=CC=C2C=CC=1)CCCC1=CC=CC(C(F)(F)F)=C1 VDHAWDNDOKGFTD-MRXNPFEDSA-N 0.000 title claims abstract description 148
- 229940116949 sensipar Drugs 0.000 title claims abstract description 139
- 238000000034 method Methods 0.000 title claims abstract description 84
- 208000020832 chronic kidney disease Diseases 0.000 claims abstract description 62
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 9
- 239000011707 mineral Substances 0.000 claims abstract description 9
- 208000020084 Bone disease Diseases 0.000 claims abstract description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 97
- 238000011282 treatment Methods 0.000 claims description 70
- 230000000694 effects Effects 0.000 claims description 60
- 210000002990 parathyroid gland Anatomy 0.000 claims description 39
- 208000037157 Azotemia Diseases 0.000 claims description 17
- 125000002091 cationic group Chemical group 0.000 claims description 17
- 208000009852 uremia Diseases 0.000 claims description 17
- 206010020718 hyperplasia Diseases 0.000 claims description 14
- 201000006370 kidney failure Diseases 0.000 claims description 13
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 12
- 230000000762 glandular Effects 0.000 claims description 12
- 210000004872 soft tissue Anatomy 0.000 claims description 11
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 9
- 102000003982 Parathyroid hormone Human genes 0.000 abstract description 139
- 108090000445 Parathyroid hormone Proteins 0.000 abstract description 139
- 239000000199 parathyroid hormone Substances 0.000 abstract description 139
- 210000002966 serum Anatomy 0.000 abstract description 94
- 239000011575 calcium Substances 0.000 abstract description 90
- 229910052791 calcium Inorganic materials 0.000 abstract description 85
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 82
- 210000003734 kidney Anatomy 0.000 abstract description 39
- 239000000203 mixture Substances 0.000 abstract description 32
- 238000001631 haemodialysis Methods 0.000 abstract description 30
- 208000005770 Secondary Hyperparathyroidism Diseases 0.000 abstract description 28
- 108010050543 Calcium-Sensing Receptors Proteins 0.000 abstract description 22
- 229960001319 parathyroid hormone Drugs 0.000 abstract description 11
- 230000003907 kidney function Effects 0.000 abstract description 10
- 239000000556 agonist Substances 0.000 abstract description 5
- 206010020707 Hyperparathyroidism primary Diseases 0.000 abstract description 4
- 201000000981 Primary Hyperparathyroidism Diseases 0.000 abstract description 4
- 102000013830 Calcium-Sensing Receptors Human genes 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 description 120
- 238000012545 processing Methods 0.000 description 60
- 241001465754 Metazoa Species 0.000 description 57
- 241000700159 Rattus Species 0.000 description 54
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 48
- 125000000539 amino acid group Chemical group 0.000 description 42
- 239000003153 chemical reaction reagent Substances 0.000 description 42
- 210000004907 gland Anatomy 0.000 description 37
- 229930003316 Vitamin D Natural products 0.000 description 32
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 32
- 235000019166 vitamin D Nutrition 0.000 description 32
- 239000011710 vitamin D Substances 0.000 description 32
- 150000003710 vitamin D derivatives Chemical class 0.000 description 32
- 229940046008 vitamin d Drugs 0.000 description 32
- 239000003814 drug Substances 0.000 description 29
- 102000004196 processed proteins & peptides Human genes 0.000 description 29
- 229920001184 polypeptide Polymers 0.000 description 27
- 210000004369 blood Anatomy 0.000 description 26
- 239000008280 blood Substances 0.000 description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
- 239000002609 medium Substances 0.000 description 26
- 230000009467 reduction Effects 0.000 description 26
- 235000001014 amino acid Nutrition 0.000 description 24
- 239000012071 phase Substances 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 23
- 230000008859 change Effects 0.000 description 22
- 229940109239 creatinine Drugs 0.000 description 22
- 238000001990 intravenous administration Methods 0.000 description 22
- 239000008194 pharmaceutical composition Substances 0.000 description 22
- 201000010099 disease Diseases 0.000 description 21
- 229930024421 Adenine Natural products 0.000 description 20
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 20
- 102100035650 Extracellular calcium-sensing receptor Human genes 0.000 description 20
- 229960000643 adenine Drugs 0.000 description 20
- 229910052698 phosphorus Inorganic materials 0.000 description 20
- -1 3- Mercapto propyl Chemical group 0.000 description 19
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 19
- 239000011574 phosphorus Substances 0.000 description 19
- 208000004434 Calcinosis Diseases 0.000 description 18
- 230000002308 calcification Effects 0.000 description 18
- 230000001965 increasing effect Effects 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- 201000002980 Hyperparathyroidism Diseases 0.000 description 16
- 238000000502 dialysis Methods 0.000 description 16
- 229920001223 polyethylene glycol Polymers 0.000 description 16
- 239000002202 Polyethylene glycol Substances 0.000 description 15
- 150000001413 amino acids Chemical class 0.000 description 15
- 210000000988 bone and bone Anatomy 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 238000005259 measurement Methods 0.000 description 15
- 210000002381 plasma Anatomy 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 230000001225 therapeutic effect Effects 0.000 description 14
- 238000011160 research Methods 0.000 description 13
- 210000003491 skin Anatomy 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 208000006386 Bone Resorption Diseases 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- 230000024279 bone resorption Effects 0.000 description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 11
- 239000000902 placebo Substances 0.000 description 11
- 229940068196 placebo Drugs 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 238000012384 transportation and delivery Methods 0.000 description 11
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 10
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 10
- 229910019142 PO4 Inorganic materials 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 238000012937 correction Methods 0.000 description 10
- 230000006378 damage Effects 0.000 description 10
- 239000010452 phosphate Substances 0.000 description 10
- 229920000642 polymer Polymers 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 9
- 210000004899 c-terminal region Anatomy 0.000 description 9
- 229960003315 cinacalcet Drugs 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- HKXBNHCUPKIYDM-CGMHZMFXSA-N doxercalciferol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C HKXBNHCUPKIYDM-CGMHZMFXSA-N 0.000 description 8
- 230000002500 effect on skin Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 7
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 7
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 7
- 102000014128 RANK Ligand Human genes 0.000 description 7
- 108010025832 RANK Ligand Proteins 0.000 description 7
- 229910001424 calcium ion Inorganic materials 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 235000018417 cysteine Nutrition 0.000 description 7
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 238000000151 deposition Methods 0.000 description 7
- 229960000413 doxercalciferol Drugs 0.000 description 7
- 201000000523 end stage renal failure Diseases 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000011552 rat model Methods 0.000 description 7
- 150000003573 thiols Chemical group 0.000 description 7
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
- 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 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004204 blood vessel Anatomy 0.000 description 6
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 6
- 239000011612 calcitriol Substances 0.000 description 6
- 229960005084 calcitriol Drugs 0.000 description 6
- 235000020964 calcitriol Nutrition 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 230000008021 deposition Effects 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 230000000322 hemodialysis Effects 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- 230000000849 parathyroid Effects 0.000 description 6
- 238000007911 parenteral administration Methods 0.000 description 6
- 229960000987 paricalcitol Drugs 0.000 description 6
- BPKAHTKRCLCHEA-UBFJEZKGSA-N paricalcitol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](\C=C\[C@H](C)C(C)(C)O)C)=C\C=C1C[C@@H](O)C[C@H](O)C1 BPKAHTKRCLCHEA-UBFJEZKGSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000003127 radioimmunoassay Methods 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 6
- 235000002374 tyrosine Nutrition 0.000 description 6
- 210000002700 urine Anatomy 0.000 description 6
- 239000004474 valine Substances 0.000 description 6
- 102000009310 vitamin D receptors Human genes 0.000 description 6
- 108050000156 vitamin D receptors Proteins 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000003442 weekly effect Effects 0.000 description 6
- 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 5
- 102000012422 Collagen Type I Human genes 0.000 description 5
- 108010022452 Collagen Type I Proteins 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 5
- 210000000709 aorta Anatomy 0.000 description 5
- 230000002092 calcimimetic effect Effects 0.000 description 5
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 238000004043 dyeing Methods 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 208000028208 end stage renal disease Diseases 0.000 description 5
- 230000029142 excretion Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 229960001340 histamine Drugs 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 229960000310 isoleucine Drugs 0.000 description 5
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 235000008521 threonine Nutrition 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 4
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 102000004067 Osteocalcin Human genes 0.000 description 4
- 108090000573 Osteocalcin Proteins 0.000 description 4
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 4
- 108010050808 Procollagen Proteins 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 102100032236 Tumor necrosis factor receptor superfamily member 11B Human genes 0.000 description 4
- 238000002679 ablation Methods 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 229960003121 arginine Drugs 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 235000003704 aspartic acid Nutrition 0.000 description 4
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 235000013922 glutamic acid Nutrition 0.000 description 4
- 239000004220 glutamic acid Substances 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 235000004554 glutamine Nutrition 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 210000000963 osteoblast Anatomy 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000006320 pegylation Effects 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 230000035479 physiological effects, processes and functions Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 3
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 3
- 108010051457 Acid Phosphatase Proteins 0.000 description 3
- 102000013563 Acid Phosphatase Human genes 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 102000055006 Calcitonin Human genes 0.000 description 3
- 108060001064 Calcitonin Proteins 0.000 description 3
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical group Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 108090000569 Fibroblast Growth Factor-23 Proteins 0.000 description 3
- 102100024802 Fibroblast growth factor 23 Human genes 0.000 description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
- 208000037147 Hypercalcaemia Diseases 0.000 description 3
- 208000013038 Hypocalcemia Diseases 0.000 description 3
- 108010035042 Osteoprotegerin Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 238000011892 Von Kossa's method Methods 0.000 description 3
- ZQBZAOZWBKABNC-UHFFFAOYSA-N [P].[Ca] Chemical compound [P].[Ca] ZQBZAOZWBKABNC-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 3
- 229960002535 alfacalcidol Drugs 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 3
- 229960004015 calcitonin Drugs 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 229960000478 cinacalcet hydrochloride Drugs 0.000 description 3
- QANQWUQOEJZMLL-PKLMIRHRSA-N cinacalcet hydrochloride Chemical compound Cl.N([C@H](C)C=1C2=CC=CC=C2C=CC=1)CCCC1=CC=CC(C(F)(F)F)=C1 QANQWUQOEJZMLL-PKLMIRHRSA-N 0.000 description 3
- 238000011284 combination treatment Methods 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000001177 diphosphate Substances 0.000 description 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 3
- 235000011180 diphosphates Nutrition 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 238000002657 hormone replacement therapy Methods 0.000 description 3
- 208000030915 hypercalcemia disease Diseases 0.000 description 3
- 230000000705 hypocalcaemia Effects 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 230000016507 interphase Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 3
- 231100000572 poisoning Toxicity 0.000 description 3
- 230000000607 poisoning effect Effects 0.000 description 3
- 229920000747 poly(lactic acid) Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000004043 responsiveness Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 3
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 3
- 235000004400 serine Nutrition 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 210000000434 stratum corneum Anatomy 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- BPKAHTKRCLCHEA-FOPGHSPUSA-N 19-Nor-1-α,25-dihydroxyvitamin D2 Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](C=C[C@H](C)C(C)(C)O)C)=CC=C1C[C@@H](O)C[C@H](O)C1 BPKAHTKRCLCHEA-FOPGHSPUSA-N 0.000 description 2
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 102000006996 Aryldialkylphosphatase Human genes 0.000 description 2
- 108010008184 Aryldialkylphosphatase Proteins 0.000 description 2
- 238000010152 Bonferroni least significant difference Methods 0.000 description 2
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 description 2
- FFFHZYDWPBMWHY-GSVOUGTGSA-N D-Homocysteine Chemical compound OC(=O)[C@H](N)CCS FFFHZYDWPBMWHY-GSVOUGTGSA-N 0.000 description 2
- ZAHDXEIQWWLQQL-IHRRRGAJSA-N Deoxypyridinoline Chemical compound OC(=O)[C@@H](N)CCCC[N+]1=CC(O)=C(C[C@H](N)C([O-])=O)C(CC[C@H](N)C(O)=O)=C1 ZAHDXEIQWWLQQL-IHRRRGAJSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010053070 Glutathione Disulfide Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 101000589873 Homo sapiens Parathyroid hormone/parathyroid hormone-related peptide receptor Proteins 0.000 description 2
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 2
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 102100032256 Parathyroid hormone/parathyroid hormone-related peptide receptor Human genes 0.000 description 2
- 206010033964 Parathyroid tumour benign Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- LCYXYLLJXMAEMT-SAXRGWBVSA-N Pyridinoline Chemical compound OC(=O)[C@@H](N)CCC1=C[N+](C[C@H](O)CC[C@H](N)C([O-])=O)=CC(O)=C1C[C@H](N)C(O)=O LCYXYLLJXMAEMT-SAXRGWBVSA-N 0.000 description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N Pyridoxal Chemical compound CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000010513 Stupor Diseases 0.000 description 2
- 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 2
- 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 2
- NYTOUQBROMCLBJ-UHFFFAOYSA-N Tetranitromethane Chemical compound [O-][N+](=O)C([N+]([O-])=O)([N+]([O-])=O)[N+]([O-])=O NYTOUQBROMCLBJ-UHFFFAOYSA-N 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- RGCKGOZRHPZPFP-UHFFFAOYSA-N alizarin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 239000000022 bacteriostatic agent Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000004094 calcium homeostasis Effects 0.000 description 2
- 230000003185 calcium uptake Effects 0.000 description 2
- 230000021523 carboxylation Effects 0.000 description 2
- 238000006473 carboxylation reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000024924 glomerular filtration Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000003694 hair properties Effects 0.000 description 2
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 230000000148 hypercalcaemia Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 230000002584 immunomodulator Effects 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003978 infusion fluid Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000000608 laser ablation Methods 0.000 description 2
- GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 description 2
- 229960002367 lasofoxifene Drugs 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 150000002634 lipophilic molecules Chemical class 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000013059 nephrectomy Methods 0.000 description 2
- 230000002232 neuromuscular Effects 0.000 description 2
- 125000001741 organic sulfur group Chemical group 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 201000003686 parathyroid adenoma Diseases 0.000 description 2
- 201000003913 parathyroid carcinoma Diseases 0.000 description 2
- 208000014643 parathyroid gland adenoma Diseases 0.000 description 2
- 208000017954 parathyroid gland carcinoma Diseases 0.000 description 2
- 230000000505 pernicious effect Effects 0.000 description 2
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 229940126409 proton pump inhibitor Drugs 0.000 description 2
- 239000000612 proton pump inhibitor Substances 0.000 description 2
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 2
- 229960001327 pyridoxal phosphate Drugs 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 229940052212 zemplar Drugs 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 1
- HGFOOLONGOBCMP-IBGZPJMESA-N (3s)-3-(6-methoxypyridin-3-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]imidazolidin-1-yl]propanoic acid Chemical compound C1=NC(OC)=CC=C1[C@H](CC(O)=O)N1C(=O)N(CCCC=2N=C3NCCCC3=CC=2)CC1 HGFOOLONGOBCMP-IBGZPJMESA-N 0.000 description 1
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 1
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical group CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 1
- JQPFYXFVUKHERX-UHFFFAOYSA-N 2-hydroxy-2-cyclohexen-1-one Natural products OC1=CCCCC1=O JQPFYXFVUKHERX-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WRLFSJXJGJBFJQ-WPUCQFJDSA-N Calcifediol monohydrate Chemical compound O.C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)CCC1=C WRLFSJXJGJBFJQ-WPUCQFJDSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 229940122156 Cathepsin K inhibitor Drugs 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 208000026372 Congenital cystic kidney disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 108020003264 Cotransporters Proteins 0.000 description 1
- 102000034534 Cotransporters Human genes 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- SNDPXSYFESPGGJ-SCSAIBSYSA-N D-2-aminopentanoic acid Chemical compound CCC[C@@H](N)C(O)=O SNDPXSYFESPGGJ-SCSAIBSYSA-N 0.000 description 1
- DCXYFEDJOCDNAF-UWTATZPHSA-N D-Asparagine Chemical compound OC(=O)[C@H](N)CC(N)=O DCXYFEDJOCDNAF-UWTATZPHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-RFZPGFLSSA-N D-Isoleucine Chemical compound CC[C@@H](C)[C@@H](N)C(O)=O AGPKZVBTJJNPAG-RFZPGFLSSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-GSVOUGTGSA-N D-glutamine Chemical compound OC(=O)[C@H](N)CCC(N)=O ZDXPYRJPNDTMRX-GSVOUGTGSA-N 0.000 description 1
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 description 1
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 125000000296 D-methionine group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C([H])([H])C([H])([H])SC([H])([H])[H] 0.000 description 1
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical compound C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 description 1
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 description 1
- OUYCCCASQSFEME-MRVPVSSYSA-N D-tyrosine Chemical compound OC(=O)[C@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-MRVPVSSYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-SCSAIBSYSA-N D-valine Chemical compound CC(C)[C@@H](N)C(O)=O KZSNJWFQEVHDMF-SCSAIBSYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 240000001879 Digitalis lutea Species 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- RCPOVANIIKXVTB-YPPRVYOWSA-N Galactosylhydroxylysine Chemical compound NCCCC[C@@H](C(O)=O)N(O)C1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O RCPOVANIIKXVTB-YPPRVYOWSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 101001055531 Homo sapiens Matrix extracellular phosphoglycoprotein Proteins 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 206010020590 Hypercalciuria Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 208000000913 Kidney Calculi Diseases 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- RFQHCLMGLJGZNV-UXXOMSPDSA-N Lunacalcipol Chemical compound C1(/[C@@H]2CC=C([C@]2(CCC1)C)[C@@H](C\C=C\S(=O)(=O)C(C)(C)C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C RFQHCLMGLJGZNV-UXXOMSPDSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100026142 Matrix extracellular phosphoglycoprotein Human genes 0.000 description 1
- 206010027635 Milk-alkali syndrome Diseases 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010029148 Nephrolithiasis Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 206010031149 Osteitis Diseases 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000027067 Paget disease of bone Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 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
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropyl alcohol Natural products CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- 102100037170 Phosphate carrier protein, mitochondrial Human genes 0.000 description 1
- 101710128683 Phosphate carrier protein, mitochondrial Proteins 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000135309 Processus Species 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- 206010037601 Pyelonephritis chronic Diseases 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 206010039020 Rhabdomyolysis Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
- 108091006182 SLC34 Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 206010049418 Sudden Cardiac Death Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 1
- OBNDGIHQAIXEAO-UHFFFAOYSA-N [O].[Si] Chemical compound [O].[Si] OBNDGIHQAIXEAO-UHFFFAOYSA-N 0.000 description 1
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- BVCZEBOGSOYJJT-UHFFFAOYSA-N ammonium carbamate Chemical compound [NH4+].NC([O-])=O BVCZEBOGSOYJJT-UHFFFAOYSA-N 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000001636 atomic emission spectroscopy Methods 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- XABJJJZIQNZSIM-UHFFFAOYSA-N azane;phenol Chemical compound [NH4+].[O-]C1=CC=CC=C1 XABJJJZIQNZSIM-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 238000011953 bioanalysis Methods 0.000 description 1
- 239000003150 biochemical marker Substances 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 208000016738 bone Paget disease Diseases 0.000 description 1
- 208000018339 bone inflammation disease Diseases 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 229910010277 boron hydride Inorganic materials 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001668 calcitriol derivatives Chemical class 0.000 description 1
- 208000025616 calcium-alkali syndrome Diseases 0.000 description 1
- 229940121399 calcium-sensing receptor agonists Drugs 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000004651 carbonic acid esters Chemical class 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 201000006368 chronic pyelonephritis Diseases 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 238000009535 clinical urine test Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940035811 conjugated estrogen Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 210000004351 coronary vessel Anatomy 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
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical compound O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 1
- 229920006237 degradable polymer Polymers 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 239000008355 dextrose injection Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000011984 electrochemiluminescence immunoassay Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000004993 emission spectroscopy Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- QTTMOCOWZLSYSV-QWAPEVOJSA-M equilin sodium sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4C3=CCC2=C1 QTTMOCOWZLSYSV-QWAPEVOJSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 201000000080 familial hypocalciuric hypercalcemia Diseases 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940062743 hectorol Drugs 0.000 description 1
- 210000005096 hematological system Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229940124280 l-arginine Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910001092 metal group alloy Inorganic materials 0.000 description 1
- NEGQCMNHXHSFGU-UHFFFAOYSA-N methyl pyridine-2-carboximidate Chemical compound COC(=N)C1=CC=CC=N1 NEGQCMNHXHSFGU-UHFFFAOYSA-N 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000005404 monopole Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 201000000173 nephrocalcinosis Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000001599 osteoclastic effect Effects 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 208000025061 parathyroid hyperplasia Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- IBIRZFNPWYRWOG-UHFFFAOYSA-N phosphane;phosphoric acid Chemical compound P.OP(O)(O)=O IBIRZFNPWYRWOG-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000111 poly(butyric acid) Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920001306 poly(lactide-co-caprolactone) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 229920006149 polyester-amide block copolymer Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 229960003581 pyridoxal Drugs 0.000 description 1
- 235000008164 pyridoxal Nutrition 0.000 description 1
- 239000011674 pyridoxal Substances 0.000 description 1
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 1
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 1
- 238000007674 radiofrequency ablation Methods 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 108700015048 receptor decoy activity proteins Proteins 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229940089617 risedronate Drugs 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 208000014221 sudden cardiac arrest Diseases 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000004035 thiopropyl group Chemical group [H]SC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000036228 toxication Effects 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/20—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of PTH
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161558389P | 2011-11-10 | 2011-11-10 | |
| US61/558389 | 2011-11-10 | ||
| CN201280066707.1A CN104168955A (zh) | 2011-11-10 | 2012-11-12 | 拟钙剂及其使用方法 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280066707.1A Division CN104168955A (zh) | 2011-11-10 | 2012-11-12 | 拟钙剂及其使用方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109985228A true CN109985228A (zh) | 2019-07-09 |
Family
ID=47258113
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910103503.4A Pending CN109985228A (zh) | 2011-11-10 | 2012-11-12 | 拟钙剂及其使用方法 |
| CN201280066707.1A Pending CN104168955A (zh) | 2011-11-10 | 2012-11-12 | 拟钙剂及其使用方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280066707.1A Pending CN104168955A (zh) | 2011-11-10 | 2012-11-12 | 拟钙剂及其使用方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US20140315809A1 (https=) |
| EP (1) | EP2776129B2 (https=) |
| JP (2) | JP6204369B2 (https=) |
| CN (2) | CN109985228A (https=) |
| AU (1) | AU2012335009B2 (https=) |
| CA (1) | CA2854911C (https=) |
| HK (1) | HK1202086A1 (https=) |
| MX (1) | MX355063B (https=) |
| WO (1) | WO2013071262A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022257940A1 (zh) * | 2021-06-08 | 2022-12-15 | 北京拓界生物医药科技有限公司 | 钙敏感受体激动剂化合物的盐酸盐及药物组合物和其应用 |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2559228C (en) | 2004-04-21 | 2016-06-21 | Enobia Pharma Inc. | Bone delivery conjugates and method of using same to target proteins to bone |
| US8999932B2 (en) | 2009-07-29 | 2015-04-07 | Kai Pharmaceuticals, Inc. | Therapeutic agents for reducing parathyroid hormone levels |
| MA38724B1 (fr) | 2013-06-28 | 2017-11-30 | Amgen Inc | Formulation liquide stable d'amg 416 (velcalcétide) |
| WO2016007873A1 (en) | 2014-07-11 | 2016-01-14 | The Regents Of The University Of Michigan | Compositions and methods for treating craniosynostosis |
| US20170304286A1 (en) * | 2014-10-24 | 2017-10-26 | Launx Biomedical Co., Ltd. | New indication of paroxetine pharmaceutical composition for treating cancer |
| MX389350B (es) | 2014-12-05 | 2025-03-19 | Alexion Pharma Inc | Fosfatasas alcalinas recombinantes y usos de las mismas para el tratamiento de convulsiones. |
| US9539264B2 (en) | 2014-12-30 | 2017-01-10 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-nor-(20S)-1-alpha,25-dihydroxyvitamin D3 to treat secondary hyperparathyroidism in patients previously treated with calcimimetics |
| JP6868561B2 (ja) | 2015-01-28 | 2021-05-12 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | アルカリホスファターゼ欠損を有する被験者を治療する方法 |
| CN108350440A (zh) | 2015-08-17 | 2018-07-31 | 阿雷克森制药公司 | 碱性磷酸酯的制造 |
| JP6868617B2 (ja) | 2015-09-28 | 2021-05-12 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 低ホスファターゼ血症の組織非特異的アルカリホスファターゼ（ｔｎｓａｌｐ）酵素補充療法に有効な投薬計画の特定 |
| JP2018533571A (ja) | 2015-10-30 | 2018-11-15 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 患者の頭蓋縫合早期癒合症を治療するための方法 |
| CN106928320B (zh) * | 2015-12-31 | 2021-01-15 | 深圳翰宇药业股份有限公司 | 一种合成Etelcalcetide的方法 |
| WO2017155569A1 (en) | 2016-03-08 | 2017-09-14 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in children |
| US10898549B2 (en) | 2016-04-01 | 2021-01-26 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in adolescents and adults |
| JP7613826B2 (ja) | 2016-04-01 | 2025-01-15 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | アルカリホスファターゼによって筋力低下を治療すること |
| US10988744B2 (en) | 2016-06-06 | 2021-04-27 | Alexion Pharmaceuticals, Inc. | Method of producing alkaline phosphatase |
| EP3500289B1 (en) | 2016-08-18 | 2024-10-09 | Alexion Pharmaceuticals, Inc. | Asfotase alfa for use in treating tracheobronchomalacia |
| EP3600383A4 (en) | 2017-03-31 | 2020-10-28 | Alexion Pharmaceuticals, Inc. | METHODS OF TREATMENT OF HYPOPHOSPHATASIA (HPP) IN ADULTS AND ADOLESCENTS |
| US11913039B2 (en) | 2018-03-30 | 2024-02-27 | Alexion Pharmaceuticals, Inc. | Method for producing recombinant alkaline phosphatase |
| US12268733B2 (en) | 2018-08-10 | 2025-04-08 | Alexion Pharmaceuticals, Inc. | Methods of treating neurofibromatosis type 1 and related conditions with alkaline phosphatase |
| US11450405B2 (en) * | 2018-10-18 | 2022-09-20 | Fresenius Medical Care Holdings, Inc. | Techniques for modeling parathyroid gland functionality and calcimimetic drug activity |
| CA3161266A1 (en) | 2019-12-09 | 2021-06-17 | Alexion Pharmaceuticals, Inc. | Alkaline phosphatase polypeptides and methods of use thereof |
| WO2021115272A1 (zh) * | 2019-12-09 | 2021-06-17 | 北京拓界生物医药科技有限公司 | 钙敏感受体激动剂化合物及其应用 |
| AU2021337652B2 (en) | 2020-09-04 | 2025-01-30 | Alexion Pharmaceuticals, Inc. | Methods for treating bone mineralization disorders |
| EP4212542A4 (en) * | 2020-09-10 | 2024-08-28 | Shaanxi Micot Technology Co., Ltd. | BISPECIFIC FUSION POLYPEPTIDE COMPOUND |
| BR112023016048A2 (pt) | 2021-02-12 | 2023-11-14 | Alexion Pharma Inc | Polipeptídeos de fosfatase alcalina e métodos de uso dos mesmos |
| EP4353248A4 (en) * | 2021-06-08 | 2024-10-23 | Beijing Tuo Jie Biopharmaceutical Co. Ltd. | CALCIUM-SENSITIVE RECEPTOR AGONIST COMPOSITION AND APPLICATION THEREOF |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101184508A (zh) * | 2005-03-17 | 2008-05-21 | 安姆根有限公司 | 减少钙化的方法 |
| US20080261926A1 (en) * | 2007-04-02 | 2008-10-23 | Liu Julie F | Pharmaceutical Calcimimetics |
| US20110028394A1 (en) * | 2009-07-29 | 2011-02-03 | Kai Pharmaceuticals, Inc. | Therapeutic agents for reducing parathyroid hormone levels |
| WO2011015859A1 (en) * | 2009-08-03 | 2011-02-10 | Ineos Healthcare Limited | Method |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5602116A (en) | 1988-08-02 | 1997-02-11 | Bone Care International, Inc. | Method for treating and preventing secondary hyperparathyroidism |
| US5869473A (en) | 1988-08-02 | 1999-02-09 | Bone Care International, Inc. | Method for treating and preventing hyperparathyroidism |
| US5246925A (en) | 1989-03-09 | 1993-09-21 | Wisconsin Alumni Research Foundation | 19-nor-vitamin D compounds for use in treating hyperparathyroidism |
| CA1333616C (en) | 1989-03-09 | 1994-12-20 | Hector F. Deluca | 19-nor-vitamin d compounds |
| US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| US6011068A (en) | 1991-08-23 | 2000-01-04 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US6031003A (en) | 1991-08-23 | 2000-02-29 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US5886026A (en) | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| JP4142743B2 (ja) * | 1996-07-31 | 2008-09-03 | ザ・ジェネラル・ホスピタル・コーポレイション | 副甲状腺ホルモンに関連する新規ペプチド類似体 |
| US6274169B1 (en) | 1999-08-02 | 2001-08-14 | Abbott Laboratories | Low oxygen content compostions of 1α, 25-dihydroxycholecalciferol |
| US6051567A (en) | 1999-08-02 | 2000-04-18 | Abbott Laboratories | Low oxygen content compositions of 1α, 25-dihydroxycholecalciferol |
| AU7895601A (en) | 2000-07-18 | 2002-01-30 | Bone Care Int Inc | Stabilized 1alpha-hydroxy vitamin d |
| WO2003013543A1 (en) * | 2001-08-08 | 2003-02-20 | Genomed, Llc | Treatment or prevention of acute renal failure |
| JP5645408B2 (ja) | 2006-11-16 | 2014-12-24 | カイ ファーマシューティカルズ インコーポレーティッド | 副甲状腺機能亢進症および高カルシウム血症性障害の治療のためのポリカチオン性カルシウムモジュレーターペプチド |
-
2012
- 2012-11-12 CN CN201910103503.4A patent/CN109985228A/zh active Pending
- 2012-11-12 CA CA2854911A patent/CA2854911C/en active Active
- 2012-11-12 MX MX2014005662A patent/MX355063B/es active IP Right Grant
- 2012-11-12 AU AU2012335009A patent/AU2012335009B2/en active Active
- 2012-11-12 CN CN201280066707.1A patent/CN104168955A/zh active Pending
- 2012-11-12 WO PCT/US2012/064717 patent/WO2013071262A1/en not_active Ceased
- 2012-11-12 JP JP2014541386A patent/JP6204369B2/ja active Active
- 2012-11-12 HK HK15102648.5A patent/HK1202086A1/xx unknown
- 2012-11-12 EP EP12791926.4A patent/EP2776129B2/en active Active
- 2012-11-12 US US14/357,702 patent/US20140315809A1/en not_active Abandoned
-
2016
- 2016-03-01 US US15/057,742 patent/US20160175383A1/en not_active Abandoned
-
2017
- 2017-05-23 US US15/603,279 patent/US20170252397A1/en not_active Abandoned
- 2017-06-23 JP JP2017123032A patent/JP2017160269A/ja not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101184508A (zh) * | 2005-03-17 | 2008-05-21 | 安姆根有限公司 | 减少钙化的方法 |
| US20080261926A1 (en) * | 2007-04-02 | 2008-10-23 | Liu Julie F | Pharmaceutical Calcimimetics |
| US20110028394A1 (en) * | 2009-07-29 | 2011-02-03 | Kai Pharmaceuticals, Inc. | Therapeutic agents for reducing parathyroid hormone levels |
| WO2011015859A1 (en) * | 2009-08-03 | 2011-02-10 | Ineos Healthcare Limited | Method |
Non-Patent Citations (3)
| Title |
|---|
| MUHAMMAD等: ""Survey of Attitudes of Physicians toward the Current Evaluation and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)"", 《SAUDI J KIDNEY DIS TRANSPL》 * |
| 张建荣等: "《慢性肾脏病继发性甲旁亢》", 31 January 2010 * |
| 杨义生: "继发性甲状旁腺功能亢进治疗新药cinacalcet", 《世界临床药物》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022257940A1 (zh) * | 2021-06-08 | 2022-12-15 | 北京拓界生物医药科技有限公司 | 钙敏感受体激动剂化合物的盐酸盐及药物组合物和其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20140315809A1 (en) | 2014-10-23 |
| MX2014005662A (es) | 2014-11-10 |
| CN104168955A (zh) | 2014-11-26 |
| CA2854911C (en) | 2019-09-24 |
| EP2776129A1 (en) | 2014-09-17 |
| AU2012335009B2 (en) | 2017-08-31 |
| JP2015502346A (ja) | 2015-01-22 |
| JP2017160269A (ja) | 2017-09-14 |
| HK1202086A1 (en) | 2015-09-18 |
| AU2012335009A1 (en) | 2014-05-29 |
| JP6204369B2 (ja) | 2017-09-27 |
| EP2776129B2 (en) | 2020-06-17 |
| US20170252397A1 (en) | 2017-09-07 |
| EP2776129B1 (en) | 2017-03-29 |
| MX355063B (es) | 2018-04-04 |
| CA2854911A1 (en) | 2013-05-16 |
| US20160175383A1 (en) | 2016-06-23 |
| WO2013071262A1 (en) | 2013-05-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109985228A (zh) | 拟钙剂及其使用方法 | |
| US20240116983A1 (en) | Therapeutic agents for reducing parathyroid hormone levels | |
| HK1241270A1 (en) | Therapeutic agents for reducing parathyroid hormone levels | |
| HK1241270B (en) | Therapeutic agents for reducing parathyroid hormone levels | |
| HK1167108B (en) | Therapeutic agents for reducing parathyroid hormone levels |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |