CA2911205A1 - Bone-selective osteogenic oxysterol-bone targeting agents - Google Patents
Bone-selective osteogenic oxysterol-bone targeting agents Download PDFInfo
- Publication number
- CA2911205A1 CA2911205A1 CA2911205A CA2911205A CA2911205A1 CA 2911205 A1 CA2911205 A1 CA 2911205A1 CA 2911205 A CA2911205 A CA 2911205A CA 2911205 A CA2911205 A CA 2911205A CA 2911205 A1 CA2911205 A1 CA 2911205A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- bone
- hydrogen
- subject
- osteogenic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000002188 osteogenic effect Effects 0.000 title abstract description 36
- 210000000988 bone and bone Anatomy 0.000 title description 47
- 230000008685 targeting Effects 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 130
- 208000020084 Bone disease Diseases 0.000 claims abstract description 16
- 230000008410 smoothened signaling pathway Effects 0.000 claims abstract description 8
- 210000004027 cell Anatomy 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 30
- 238000000338 in vitro Methods 0.000 claims description 29
- 230000000694 effects Effects 0.000 claims description 26
- 210000001519 tissue Anatomy 0.000 claims description 25
- 208000001132 Osteoporosis Diseases 0.000 claims description 24
- 241001465754 Metazoa Species 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 238000001727 in vivo Methods 0.000 claims description 15
- 210000000963 osteoblast Anatomy 0.000 claims description 14
- 208000010392 Bone Fractures Diseases 0.000 claims description 12
- 210000000056 organ Anatomy 0.000 claims description 12
- 230000004913 activation Effects 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 210000000130 stem cell Anatomy 0.000 claims description 8
- 208000029725 Metabolic bone disease Diseases 0.000 claims description 7
- 230000008901 benefit Effects 0.000 claims description 7
- 206010049088 Osteopenia Diseases 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 238000012384 transportation and delivery Methods 0.000 claims description 5
- 238000012385 systemic delivery Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 14
- 239000000203 mixture Substances 0.000 abstract description 57
- 238000011282 treatment Methods 0.000 abstract description 28
- 239000004098 Tetracycline Substances 0.000 abstract description 13
- 229960002180 tetracycline Drugs 0.000 abstract description 13
- 229930101283 tetracycline Natural products 0.000 abstract description 12
- 235000019364 tetracycline Nutrition 0.000 abstract description 12
- 150000003522 tetracyclines Chemical group 0.000 abstract description 12
- 108090000371 Esterases Proteins 0.000 abstract description 5
- 239000012634 fragment Substances 0.000 abstract description 5
- GTPMKIMWTOQDDD-FLVCZDKCSA-N (3s,5s,6s,8r,9s,10r,13s,14s,17s)-17-[(2s)-2-hydroxyoctan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthrene-3,6-diol Chemical class C([C@@H]1[C@@H](O)C2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@](C)(O)CCCCCC)[C@@]2(C)CC1 GTPMKIMWTOQDDD-FLVCZDKCSA-N 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 description 38
- 239000003814 drug Substances 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 230000004927 fusion Effects 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 229940079593 drug Drugs 0.000 description 21
- 230000011164 ossification Effects 0.000 description 21
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 17
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 17
- -1 set forth herein Chemical class 0.000 description 17
- 238000009472 formulation Methods 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 230000014509 gene expression Effects 0.000 description 14
- 239000007788 liquid Substances 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000002552 dosage form Substances 0.000 description 12
- 230000011664 signaling Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 12
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 11
- 230000000975 bioactive effect Effects 0.000 description 11
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 230000009818 osteogenic differentiation Effects 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 10
- 229940122361 Bisphosphonate Drugs 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 150000004663 bisphosphonates Chemical class 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 244000060234 Gmelina philippensis Species 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 229940124597 therapeutic agent Drugs 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 239000012491 analyte Substances 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- 230000004069 differentiation Effects 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 206010017076 Fracture Diseases 0.000 description 7
- 239000002202 Polyethylene glycol Substances 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 239000007943 implant Substances 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 231100000252 nontoxic Toxicity 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 229960005309 estradiol Drugs 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000003000 nontoxic effect Effects 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 208000006386 Bone Resorption Diseases 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 5
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 5
- 102000003982 Parathyroid hormone Human genes 0.000 description 5
- 108090000445 Parathyroid hormone Proteins 0.000 description 5
- 102000002624 Sp7 Transcription Factor Human genes 0.000 description 5
- 108010043267 Sp7 Transcription Factor Proteins 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 235000003704 aspartic acid Nutrition 0.000 description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Chemical group OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000012377 drug delivery Methods 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 210000004663 osteoprogenitor cell Anatomy 0.000 description 5
- 229960001319 parathyroid hormone Drugs 0.000 description 5
- 239000000199 parathyroid hormone Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical group OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 4
- QASFUMOKHFSJGL-LAFRSMQTSA-N Cyclopamine Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H](CC2=C3C)[C@@H]1[C@@H]2CC[C@@]13O[C@@H]2C[C@H](C)CN[C@H]2[C@H]1C QASFUMOKHFSJGL-LAFRSMQTSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 4
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 4
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 4
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 4
- 240000007472 Leucaena leucocephala Species 0.000 description 4
- 241000906034 Orthops Species 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 229940124325 anabolic agent Drugs 0.000 description 4
- 239000003263 anabolic agent Substances 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000008468 bone growth Effects 0.000 description 4
- 230000024279 bone resorption Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000001582 osteoblastic effect Effects 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 108010023714 recombinant human bone morphogenetic protein-2 Proteins 0.000 description 4
- 230000008439 repair process Effects 0.000 description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 3
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 3
- 230000001594 aberrant effect Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 230000001195 anabolic effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- QASFUMOKHFSJGL-UHFFFAOYSA-N cyclopamine Natural products C1C=C2CC(O)CCC2(C)C(CC2=C3C)C1C2CCC13OC2CC(C)CNC2C1C QASFUMOKHFSJGL-UHFFFAOYSA-N 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- 229930182833 estradiol Natural products 0.000 description 3
- 235000020937 fasting conditions Nutrition 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- 230000000399 orthopedic effect Effects 0.000 description 3
- 230000001009 osteoporotic effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 3
- 239000001384 succinic acid Substances 0.000 description 3
- 229940014800 succinic anhydride Drugs 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000007910 systemic administration Methods 0.000 description 3
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 3
- MCKLJFJEQRYRQT-APGJSSKUSA-N 20-hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@](C)(O)CCCC(C)C)[C@@]1(C)CC2 MCKLJFJEQRYRQT-APGJSSKUSA-N 0.000 description 2
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101150061927 BMP2 gene Proteins 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- 208000003311 Cytochrome P-450 Enzyme Inhibitors Diseases 0.000 description 2
- 229940122280 Cytochrome P450 inhibitor Drugs 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010061246 Intervertebral disc degeneration Diseases 0.000 description 2
- 101000844802 Lacticaseibacillus rhamnosus Teichoic acid D-alanyltransferase Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 101100165560 Mus musculus Bmp7 gene Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000020307 Spinal disease Diseases 0.000 description 2
- 108010049264 Teriparatide Proteins 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 102000013814 Wnt Human genes 0.000 description 2
- 108050003627 Wnt Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 230000009815 adipogenic differentiation Effects 0.000 description 2
- 230000011759 adipose tissue development Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229960004343 alendronic acid Drugs 0.000 description 2
- 230000000390 anti-adipogenic effect Effects 0.000 description 2
- 230000000123 anti-resoprtive effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 101150067309 bmp4 gene Proteins 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 208000018180 degenerative disc disease Diseases 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 229940053641 forteo Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 230000009459 hedgehog signaling Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 208000021600 intervertebral disc degenerative disease Diseases 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 210000001847 jaw Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- LZFCBBSYZJPPIV-UHFFFAOYSA-M magnesium;hexane;bromide Chemical compound [Mg+2].[Br-].CCCCC[CH2-] LZFCBBSYZJPPIV-UHFFFAOYSA-M 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 230000004072 osteoblast differentiation Effects 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- OZZAYJQNMKMUSD-DMISRAGPSA-N pregnenolone succinate Chemical compound C1C=C2C[C@@H](OC(=O)CCC(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 OZZAYJQNMKMUSD-DMISRAGPSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229940127293 prostanoid Drugs 0.000 description 2
- 150000003814 prostanoids Chemical class 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001172 regenerating effect Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011775 sodium fluoride Substances 0.000 description 2
- 235000013024 sodium fluoride Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)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](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- RZPAXNJLEKLXNO-UHFFFAOYSA-N (20R,22R)-3beta,22-Dihydroxylcholest-5-en Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C(O)CCC(C)C)C1(C)CC2 RZPAXNJLEKLXNO-UHFFFAOYSA-N 0.000 description 1
- RZPAXNJLEKLXNO-GFKLAVDKSA-N (22R)-22-hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)[C@H](O)CCC(C)C)[C@@]1(C)CC2 RZPAXNJLEKLXNO-GFKLAVDKSA-N 0.000 description 1
- RZPAXNJLEKLXNO-QUOSNDFLSA-N (22S)-22-hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)[C@@H](O)CCC(C)C)[C@@]1(C)CC2 RZPAXNJLEKLXNO-QUOSNDFLSA-N 0.000 description 1
- FWIVDMJALNEADT-SFTDATJTSA-N (2s)-n-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1s)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]pentanamide Chemical compound C1=CC([C@H](N[C@@H](CC(C)(F)C)C(=O)NC2(CC2)C#N)C(F)(F)F)=CC=C1C1=CC=C(S(C)(=O)=O)C=C1 FWIVDMJALNEADT-SFTDATJTSA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
- QWYTUBPAXJYCTH-UHFFFAOYSA-N 2-trimethylsilylethyl carbamate Chemical compound C[Si](C)(C)CCOC(N)=O QWYTUBPAXJYCTH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 101150080498 ALP gene Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 101100448213 Caenorhabditis elegans odr-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- 206010009269 Cleft palate Diseases 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 229940124602 FDA-approved drug Drugs 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000030136 Marchiafava-Bignami Disease Diseases 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- 241000238367 Mya arenaria Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 101100062121 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cyc-1 gene Proteins 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 102000014736 Notch Human genes 0.000 description 1
- 108010070047 Notch Receptors Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 208000002565 Open Fractures Diseases 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- ORNBQBCIOKFOEO-YQUGOWONSA-N Pregnenolone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC3)C[C@@H](O)CC4)CC2)CC1 ORNBQBCIOKFOEO-YQUGOWONSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000002607 Pseudarthrosis Diseases 0.000 description 1
- 206010070774 Respiratory tract oedema Diseases 0.000 description 1
- 206010038967 Retrograde ejaculation Diseases 0.000 description 1
- 206010040102 Seroma Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 206010043903 Tobacco abuse Diseases 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating 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
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000011444 antiresorptive therapy Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- OISFUZRUIGGTSD-LJTMIZJLSA-N azane;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound N.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO OISFUZRUIGGTSD-LJTMIZJLSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000037180 bone health Effects 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 230000010478 bone regeneration Effects 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 230000001126 calcilytic effect Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 206010009259 cleft lip Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000000515 collagen sponge Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 239000007819 coupling partner Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 229960001251 denosumab Drugs 0.000 description 1
- 239000004053 dental implant Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- OGBMKVWORPGQRR-UHFFFAOYSA-N forteo Chemical compound C=1NC=NC=1CC(C(=O)NC(CC(C)C)C(=O)NC(CC(N)=O)C(=O)NC(CO)C(=O)NC(CCSC)C(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NC(C(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC=1C2=CC=CC=C2NC=1)C(=O)NC(CC(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CC(C)C)C(=O)NC(CCC(N)=O)C(=O)NC(CC(O)=O)C(=O)NC(C(C)C)C(=O)NC(CC=1N=CNC=1)C(=O)NC(CC(N)=O)C(=O)NC(CC=1C=CC=CC=1)C(O)=O)NC(=O)C(CCCCN)NC(=O)CNC(=O)C(CC(C)C)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CCSC)NC(=O)C(CC(C)C)NC(=O)C(CCC(N)=O)NC(=O)C(NC(=O)C(CCC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(N)CO)C(C)C)C(C)CC)CC1=CNC=N1 OGBMKVWORPGQRR-UHFFFAOYSA-N 0.000 description 1
- 229940001490 fosamax Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 125000005908 glyceryl ester group Chemical group 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 101150110819 hip gene Proteins 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 1
- 229950009755 odanacatib Drugs 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002138 osteoinductive effect Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229940070020 other anabolic agent in atc Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960000249 pregnenolone Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940092597 prolia Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 229940107023 reclast Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- OUKYUETWWIPKQR-UHFFFAOYSA-N saracatinib Chemical compound C1CN(C)CCN1CCOC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C3OCOC3=2)Cl)=NC=N2)C2=C1 OUKYUETWWIPKQR-UHFFFAOYSA-N 0.000 description 1
- 229950009919 saracatinib Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical class CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000009495 transient activation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Zoology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361818825P | 2013-05-02 | 2013-05-02 | |
| US61/818,825 | 2013-05-02 | ||
| PCT/US2014/036680 WO2014179756A1 (en) | 2013-05-02 | 2014-05-02 | Bone-selective osteogenic oxysterol-bone targeting agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2911205A1 true CA2911205A1 (en) | 2014-11-06 |
Family
ID=51844004
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2911205A Abandoned CA2911205A1 (en) | 2013-05-02 | 2014-05-02 | Bone-selective osteogenic oxysterol-bone targeting agents |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9683009B2 (enExample) |
| EP (1) | EP2991652A4 (enExample) |
| JP (1) | JP2016517888A (enExample) |
| CN (1) | CN105263500A (enExample) |
| AU (1) | AU2014259672A1 (enExample) |
| CA (1) | CA2911205A1 (enExample) |
| WO (1) | WO2014179756A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1993558B1 (en) | 2006-02-27 | 2014-07-30 | The Regents of The University of California | Oxysterol compounds and the hedgehog pathway |
| AU2013260059B2 (en) * | 2012-05-07 | 2017-05-18 | The Regents Of The University Of California | Oxysterol analogue Oxy133 induces osteogenesis and hedgehog signaling and inhibits adipogenesis |
| CN105263500A (zh) | 2013-05-02 | 2016-01-20 | 加利福尼亚大学董事会 | 骨选择性成骨性氧固醇-骨靶向剂 |
| GB201319776D0 (en) * | 2013-11-08 | 2013-12-25 | Allecra Therapeutics Sas | Compound |
| KR20170101940A (ko) * | 2014-12-09 | 2017-09-06 | 워쏘우 오르쏘페딕 인코포레이티드 | 스테롤 관련 화합물 및 방법 |
| US9878070B2 (en) | 2015-06-17 | 2018-01-30 | Warsaw Orthopedic, Inc. | Malleable implants including an oxysterol and methods of use |
| US9987289B2 (en) * | 2015-07-10 | 2018-06-05 | Warsaw Orthopedic, Inc. | Slow release oxysterols and methods of use |
| US9877836B2 (en) | 2015-07-10 | 2018-01-30 | Warsaw Orthopedic, Inc. | Compression resistant implants including an oxysterol and methods of use |
| US10632230B2 (en) * | 2015-07-10 | 2020-04-28 | Warsaw Orthopedic, Inc. | Implants having a high drug load of an oxysterol and methods of use |
| US12171909B2 (en) | 2015-07-10 | 2024-12-24 | Warsaw Orthopedic, Inc. | Implants having a drug load of an oxysterol and methods of use |
| US9637514B1 (en) | 2015-10-26 | 2017-05-02 | MAX BioPharma, Inc. | Oxysterols and hedgehog signaling |
| AU2016347052B2 (en) * | 2015-10-27 | 2021-03-25 | Warsaw Orthopedic, Inc. | Implants having a drug load of an oxysterol and methods of use |
| US10688222B2 (en) * | 2016-11-21 | 2020-06-23 | Warsaw Orthopedic, Inc. | Lyophilized moldable implants containing an oxysterol |
| US11384114B2 (en) | 2016-12-09 | 2022-07-12 | Warsaw Orthopedic, Inc. | Polymorphic forms of an oxysterol and methods of making them |
| AU2017386417B2 (en) | 2016-12-30 | 2022-07-14 | Frequency Therapeutics, Inc. | 1H-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells |
| US10294264B2 (en) * | 2017-04-21 | 2019-05-21 | Warsaw Orthopedic, Inc. | Oxysterol-therapeutic agent derivative for bone healing |
| US10434106B2 (en) * | 2017-05-19 | 2019-10-08 | Warsaw Orthopedic, Inc. | Oxysterol-statin compounds for bone growth |
| US11464888B2 (en) | 2017-06-12 | 2022-10-11 | Warsaw Orthopedic, Inc. | Moldable formulations containing an oxysterol in an acellular tissue matrix |
| KR102318505B1 (ko) * | 2019-04-26 | 2021-10-27 | 서울대학교산학협력단 | 골 세포 전환 재조합 단백질 및 골 표적화 분자를 포함하는 골 특이적 복합체 |
Family Cites Families (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB869007A (en) | 1956-10-03 | 1961-05-25 | Ciba Ltd | New heterocyclically substituted steroids |
| CH433275A (de) | 1963-07-09 | 1967-04-15 | Hoffmann La Roche | Verfahren zur Herstellung von 19-Alkylsteroiden |
| JPS5111114B1 (enExample) | 1969-03-14 | 1976-04-08 | ||
| US3887545A (en) | 1973-11-12 | 1975-06-03 | Hoffmann La Roche | Synthesis of 1{60 -hydroxylated cholesterol derivatives |
| US4264512A (en) | 1975-09-29 | 1981-04-28 | The Regents Of The University Of California | 3-Deoxy-1α-hydroxy- and 3-deoxy-1α,25-dihydroxycholecalciferol and processes for the preparation thereof |
| US4183852A (en) | 1977-07-18 | 1980-01-15 | Kaiser Emil T | Process for preparing 25-hydroxycholesterol |
| US4559157A (en) | 1983-04-21 | 1985-12-17 | Creative Products Resource Associates, Ltd. | Cosmetic applicator useful for skin moisturizing |
| LU84979A1 (fr) | 1983-08-30 | 1985-04-24 | Oreal | Composition cosmetique ou pharmaceutique sous forme aqueuse ou anhydre dont la phase grasse contient un polyether oligomere et polyethers oligomeres nouveaux |
| US5288641A (en) | 1984-06-04 | 1994-02-22 | Arch Development Corporation | Herpes Simplex virus as a vector |
| US4743597A (en) | 1986-01-27 | 1988-05-10 | Javitt Norman B | Composition comprising an oxygenated cholesterol and use thereof for topical treatment of diseases |
| US5219740A (en) | 1987-02-13 | 1993-06-15 | Fred Hutchinson Cancer Research Center | Retroviral gene transfer into diploid fibroblasts for gene therapy |
| US5166320A (en) | 1987-04-22 | 1992-11-24 | University Of Connecticut | Carrier system and method for the introduction of genes into mammalian cells |
| US4820508A (en) | 1987-06-23 | 1989-04-11 | Neutrogena Corporation | Skin protective composition |
| US4992478A (en) | 1988-04-04 | 1991-02-12 | Warner-Lambert Company | Antiinflammatory skin moisturizing composition and method of preparing same |
| LU87201A1 (fr) | 1988-04-14 | 1989-11-14 | Cird | Complexes a base d'anthraline et d'un sterol,leur procede d'obtention et leur utilisation en therapeutique et cosmetique |
| US4938949A (en) | 1988-09-12 | 1990-07-03 | University Of New York | Treatment of damaged bone marrow and dosage units therefor |
| JP2752788B2 (ja) | 1989-01-23 | 1998-05-18 | カイロン コーポレイション | 感染および過剰増殖障害の為の組換え療法 |
| AU648261B2 (en) | 1989-08-18 | 1994-04-21 | Novartis Vaccines And Diagnostics, Inc. | Recombinant retroviruses delivering vector constructs to target cells |
| GB8919607D0 (en) | 1989-08-30 | 1989-10-11 | Wellcome Found | Novel entities for cancer therapy |
| US5183815A (en) | 1991-01-22 | 1993-02-02 | Merck & Co., Inc. | Bone acting agents |
| GB9118465D0 (en) | 1991-08-29 | 1991-10-16 | Imperial College | Steroid sulphatase inhibitors |
| US5203975A (en) | 1991-10-29 | 1993-04-20 | E. I. Du Pont De Nemours And Company | Process for cathodic electrodeposition of a clear coating over a conductive paint layer |
| WO1993010218A1 (en) | 1991-11-14 | 1993-05-27 | The United States Government As Represented By The Secretary Of The Department Of Health And Human Services | Vectors including foreign genes and negative selective markers |
| GB9125623D0 (en) | 1991-12-02 | 1992-01-29 | Dynal As | Cell modification |
| EP0650370A4 (en) | 1992-06-08 | 1995-11-22 | Univ California | METHODS AND COMPOSITIONS TARGETED ON SPECIFIC TISSUES. |
| EP0644946A4 (en) | 1992-06-10 | 1997-03-12 | Us Health | VECTOR PARTICLES RESISTANT TO HUMAN SERUM INACTIVATION. |
| GB2269175A (en) | 1992-07-31 | 1994-02-02 | Imperial College | Retroviral vectors |
| FR2705361B1 (fr) | 1993-05-18 | 1995-08-04 | Centre Nat Rech Scient | Vecteurs viraux et utilisation en thérapie génique. |
| AU688428B2 (en) | 1993-11-09 | 1998-03-12 | Johns Hopkins University, The | Generation of high titers of recombinant AAV vectors |
| US7060450B1 (en) | 1993-12-30 | 2006-06-13 | President And Fellows Of Harvard College | Screening assays for agonists and antagonists of the hedgehog signaling pathway |
| WO1995018821A2 (en) | 1994-01-06 | 1995-07-13 | Sri International | Novel antiandrogenic agents and related pharmaceutical compositions and methods of use |
| ATE363908T1 (de) | 1996-04-09 | 2007-06-15 | Univ Edinburgh | Verwendung von 7-alpha-substituierten steroiden zur behandlung von neuropsychiatrischen erkrankungen |
| EP2311471A3 (en) | 1996-04-19 | 2013-05-15 | Osiris Therapeutics, Inc. | Regeneration and augmentation of bone using mesenchymal stem cells |
| US6893830B1 (en) | 1996-09-27 | 2005-05-17 | The Board Of Regents Of The University Of Texas System | Method of screening oxysterol activation of LXRα |
| US5840752A (en) | 1996-11-21 | 1998-11-24 | Henry; James P. | Reduction of hair growth |
| US5855920A (en) | 1996-12-13 | 1999-01-05 | Chein; Edmund Y. M. | Total hormone replacement therapy |
| US6080779A (en) | 1996-12-13 | 2000-06-27 | Osteoscreen, Inc. | Compositions and methods for stimulating bone growth |
| CN1248916A (zh) | 1997-01-24 | 2000-03-29 | 加利福尼亚大学董事会 | FXR、PPARα和LXRα激活剂恢复屏障功能、促进表皮分化和抑制增生的用途 |
| CA2289675A1 (en) | 1997-05-16 | 1998-11-26 | Akzo Nobel Nv | 20-aralkyl-5.alpha.-pregnane derivatives |
| DE19723794A1 (de) | 1997-06-06 | 1998-12-10 | Jenapharm Gmbh | Nichtestrogene Derivate des Estradiols mit antioxidativer Aktivität |
| US5929062A (en) | 1997-06-19 | 1999-07-27 | University Of Western Ontario | Oxysterol inhibition of dietary cholesterol uptake |
| WO1999000117A2 (en) | 1997-06-27 | 1999-01-07 | Ontogeny, Inc. | Neuroprotective methods and reagents |
| US20030153541A1 (en) | 1997-10-31 | 2003-08-14 | Robert Dudley | Novel anticholesterol compositions and method for using same |
| JP2002506030A (ja) | 1998-03-13 | 2002-02-26 | メルク エンド カムパニー インコーポレーテッド | 骨再吸収の阻害方法 |
| EP0943332A1 (en) | 1998-03-19 | 1999-09-22 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Prevention and treatment of adhesions |
| US6906069B1 (en) | 1999-01-08 | 2005-06-14 | Amgen Inc. | LXR modulators |
| DK1163258T3 (da) | 1999-03-09 | 2003-03-31 | Akzo Nobel Nv | Derivater af 22R-hydroxycholesta-8, 14-dien til inhiberingen af meiosis |
| US6316503B1 (en) | 1999-03-15 | 2001-11-13 | Tularik Inc. | LXR modulators |
| US6586189B2 (en) | 1999-06-18 | 2003-07-01 | City Of Hope | Screening method for PPAR-γ ligands |
| AU1291901A (en) | 1999-09-01 | 2001-03-26 | University Of British Columbia, The | Compositions and methods for modulating hdl cholesterol and triglyceride levels |
| WO2001094379A2 (en) | 2000-06-08 | 2001-12-13 | The Regents Of The University Of California | Methods and compositions for controlled synthesis of amino acid polymers |
| US20020115695A1 (en) | 2000-11-07 | 2002-08-22 | Paralkar Vishwas M. | Combination therapies for the stimulation of bone growth |
| GB0101933D0 (en) | 2001-01-25 | 2001-03-07 | Astrazeneca Ab | Therapy |
| AU2002306436A1 (en) | 2001-02-12 | 2002-10-15 | Asm America, Inc. | Improved process for deposition of semiconductor films |
| WO2002080952A2 (en) | 2001-04-09 | 2002-10-17 | Lorantis Limited | Therapeutic use and identification of modulators of a hedgehog signalling pathway or one of its target pathways |
| US20040072806A1 (en) | 2002-03-15 | 2004-04-15 | Zhi-Xing Yao | Neuroprotective spirostenol pharmaceutical compositions |
| CA2495882A1 (en) | 2002-08-29 | 2004-03-11 | The Regents Of The University Of California | Agents and methods for enhancing bone formation |
| DE10307104A1 (de) | 2003-02-19 | 2004-09-23 | Schering Ag | Antitumor wirksame 2-substituierte Estra-1,3,5(10)-trien-3-yl sulfamate |
| BRPI0412439A (pt) | 2003-07-09 | 2006-09-05 | Forbes Medi Tech Inc | compostos e composições compreendendo esteróis e/ou estanóis e inibidores de biossìntese de colesterol e uso dos mesmos no tratamento ou prevenção de uma variedade de doenças e condições |
| WO2005028616A2 (en) | 2003-07-24 | 2005-03-31 | Caritas St. Elizabeth's Medical Center Of Boston, Inc. | Morphogen compositions and methods of use thereof to treat heart disorders |
| US7341850B2 (en) | 2003-08-18 | 2008-03-11 | Wyeth | Human LXRα variants |
| US9532994B2 (en) | 2003-08-29 | 2017-01-03 | The Regents Of The University Of California | Agents and methods for enhancing bone formation by oxysterols in combination with bone morphogenic proteins |
| US7196220B2 (en) | 2003-12-24 | 2007-03-27 | University Of Louisville Research Foundation, Inc. | Bone targeting compounds for delivering agents to the bone for interaction therewith |
| JP2008502725A (ja) | 2004-06-10 | 2008-01-31 | メルク エンド カムパニー インコーポレーテッド | エストロゲン受容体モジュレーター |
| WO2006012902A2 (en) | 2004-08-02 | 2006-02-09 | Novozymes A/S | Creation of diversity in polypeptides |
| DE102004042822A1 (de) | 2004-08-31 | 2006-03-16 | Technische Universität Dresden | Verbindungen und Methoden zur Behandlung, Diagnose und Prognose bei Pankreaserkrankungen |
| US20090202660A1 (en) | 2005-04-07 | 2009-08-13 | The Regents Of The University Of California | Agents and Methods for Osteogenic Oxysterols Inhibition of Oxidative Stress on Osteogenic Cellular Differentiation |
| CN104017083A (zh) | 2005-04-15 | 2014-09-03 | 亚利桑那癌症治疗公司 | 用于治疗转移性癌症的治疗肽 |
| EP1931353A4 (en) | 2005-09-02 | 2009-07-29 | Univ California | OSTEOGENIC AND ANTI-ADIOGENIC OXYSTEROLS |
| EP1993558B1 (en) | 2006-02-27 | 2014-07-30 | The Regents of The University of California | Oxysterol compounds and the hedgehog pathway |
| WO2008011071A2 (en) | 2006-07-19 | 2008-01-24 | The Regents Of The University Of California | Interactions of hedgehog and liver x receptor signaling pathways |
| WO2008036238A2 (en) | 2006-09-19 | 2008-03-27 | Wyeth | Use of lxr modulators for the prevention and treatment of skin aging |
| GB0619860D0 (en) | 2006-10-06 | 2006-11-15 | Birkeland Innovasjon As | Treatment of insulin resistance and disorders associated therewith |
| AU2007339325A1 (en) | 2006-12-19 | 2008-07-10 | The Regents Of The University Of California | Inhibition of PPAR gamma expression by specific osteogenic oxysterols |
| AU2008218188B2 (en) * | 2007-02-23 | 2014-03-06 | University Of Louisville Research Foundation, Inc | Methods and compounds for the targeted delivery of agents to bone for interaction therewith |
| US20080221070A1 (en) * | 2007-03-06 | 2008-09-11 | Pierce William M | Methods and compounds for the targeted delivery of agents to bone for interaction therewith |
| WO2008115469A2 (en) | 2007-03-16 | 2008-09-25 | The Regents Of The University Of California | Role of hedgehog signaling in atherosclerosis and cardiovascular disease |
| CN101951915A (zh) | 2007-12-03 | 2011-01-19 | 加利福尼亚大学董事会 | 用于刺猬蛋白信号、骨诱导、抗脂肪形成和wnt信号的激活的氧固醇 |
| MY163799A (en) | 2008-02-07 | 2017-10-24 | Dsg Tech Holdings Limited | Method of making an absorbent composite and absorbent articles employing the same |
| WO2011006087A1 (en) | 2009-07-10 | 2011-01-13 | The Regents Of The University Of California | Inhibition of ppar gamma expression in preadipocyte cells by oxysterols |
| WO2011103175A2 (en) | 2010-02-16 | 2011-08-25 | The Regents Of The University Of California | Oxysterols that activate liver x receptor signaling and inhibit hedgehog signaling |
| WO2012024581A2 (en) * | 2010-08-20 | 2012-02-23 | Fate Therapeutics, Inc. | Oxysterol compounds |
| WO2012024584A2 (en) * | 2010-08-20 | 2012-02-23 | Fate Therapeutics, Inc. | Oxysterol compounds |
| WO2012024583A2 (en) * | 2010-08-20 | 2012-02-23 | Fate Therapeutics, Inc. | Oxysterol compounds |
| AU2013260059B2 (en) * | 2012-05-07 | 2017-05-18 | The Regents Of The University Of California | Oxysterol analogue Oxy133 induces osteogenesis and hedgehog signaling and inhibits adipogenesis |
| US20150140059A1 (en) | 2012-05-07 | 2015-05-21 | The Regents Of The University Of California | Novel oxysterol analogue, oxy149, induces osteogenesis and hedgehog signaling and inhibits adipogenesis |
| CN105263500A (zh) | 2013-05-02 | 2016-01-20 | 加利福尼亚大学董事会 | 骨选择性成骨性氧固醇-骨靶向剂 |
| AU2015252859B2 (en) | 2014-05-02 | 2019-11-07 | The Regents Of The University Of California | Bone-selective osteogenic oxysterol bisphosphonate analogs |
-
2014
- 2014-05-02 CN CN201480032164.0A patent/CN105263500A/zh active Pending
- 2014-05-02 EP EP14791554.0A patent/EP2991652A4/en not_active Withdrawn
- 2014-05-02 AU AU2014259672A patent/AU2014259672A1/en not_active Abandoned
- 2014-05-02 JP JP2016512081A patent/JP2016517888A/ja active Pending
- 2014-05-02 WO PCT/US2014/036680 patent/WO2014179756A1/en not_active Ceased
- 2014-05-02 US US14/888,668 patent/US9683009B2/en active Active
- 2014-05-02 CA CA2911205A patent/CA2911205A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20160159850A1 (en) | 2016-06-09 |
| AU2014259672A1 (en) | 2015-12-03 |
| US9683009B2 (en) | 2017-06-20 |
| EP2991652A1 (en) | 2016-03-09 |
| CN105263500A (zh) | 2016-01-20 |
| EP2991652A4 (en) | 2016-12-07 |
| WO2014179756A1 (en) | 2014-11-06 |
| JP2016517888A (ja) | 2016-06-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9683009B2 (en) | Bone-selective osteogenic oxysterol-bone targeting agents | |
| AU2015252859B2 (en) | Bone-selective osteogenic oxysterol bisphosphonate analogs | |
| US20150140059A1 (en) | Novel oxysterol analogue, oxy149, induces osteogenesis and hedgehog signaling and inhibits adipogenesis | |
| US9717742B2 (en) | Oxysterol analogue OXY133 induces osteogenesis and hedgehog signaling and inhibits adipogenesis | |
| US9931350B2 (en) | Anti-infective and osteogenic compositions and methods of use | |
| WO2012024584A2 (en) | Oxysterol compounds | |
| CN103739647A (zh) | 用于治疗疾病的NF-κB的非激素甾体调节剂 | |
| BR102018010042A2 (pt) | método para preparar um composto, composição farmacêutica, uso de um composto, e, composto | |
| HK1208871B (en) | Oxysterol analogue, oxy149, induces osteogenesis and hedgehog signaling and inhibits adipogenesis | |
| HK1207649B (en) | Oxysterol analogue oxy133 induces osteogenesis and hedgehog signaling and inhibits adipogenesis | |
| Wang | Targeted Delivery of Dasatinib for Accelerated Bone Fracture Repair |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20200831 |