ZA200502221B - GHRH analogues - Google Patents
GHRH analogues Download PDFInfo
- Publication number
- ZA200502221B ZA200502221B ZA200502221A ZA200502221A ZA200502221B ZA 200502221 B ZA200502221 B ZA 200502221B ZA 200502221 A ZA200502221 A ZA 200502221A ZA 200502221 A ZA200502221 A ZA 200502221A ZA 200502221 B ZA200502221 B ZA 200502221B
- Authority
- ZA
- South Africa
- Prior art keywords
- ala
- lys
- ghrh
- tyr
- leu
- Prior art date
Links
- 101710142969 Somatoliberin Proteins 0.000 title claims description 190
- 102100022831 Somatoliberin Human genes 0.000 title claims description 32
- 108010051696 Growth Hormone Proteins 0.000 claims description 110
- 102000018997 Growth Hormone Human genes 0.000 claims description 110
- 239000000122 growth hormone Substances 0.000 claims description 109
- 238000000338 in vitro Methods 0.000 claims description 53
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 52
- 230000028327 secretion Effects 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 40
- OUYCCCASQSFEME-MRVPVSSYSA-N D-tyrosine Chemical compound OC(=O)[C@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-MRVPVSSYSA-N 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 36
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 28
- 241000124008 Mammalia Species 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 239000000126 substance Substances 0.000 claims description 22
- 238000001727 in vivo Methods 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 101710198286 Growth hormone-releasing hormone receptor Proteins 0.000 claims description 14
- 102100033365 Growth hormone-releasing hormone receptor Human genes 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 13
- DEFJQIDDEAULHB-IMJSIDKUSA-N L-alanyl-L-alanine Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(O)=O DEFJQIDDEAULHB-IMJSIDKUSA-N 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 11
- 238000003786 synthesis reaction Methods 0.000 claims description 11
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 10
- 230000007812 deficiency Effects 0.000 claims description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 claims description 8
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 8
- 206010028289 Muscle atrophy Diseases 0.000 claims description 8
- 230000031018 biological processes and functions Effects 0.000 claims description 8
- 201000000585 muscular atrophy Diseases 0.000 claims description 8
- DCXYFEDJOCDNAF-UWTATZPHSA-N D-Asparagine Chemical compound OC(=O)[C@H](N)CC(N)=O DCXYFEDJOCDNAF-UWTATZPHSA-N 0.000 claims description 7
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000001243 protein synthesis Methods 0.000 claims description 7
- 230000000638 stimulation Effects 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- 230000014616 translation Effects 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 6
- 208000036119 Frailty Diseases 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 206010003549 asthenia Diseases 0.000 claims description 5
- 230000002267 hypothalamic effect Effects 0.000 claims description 5
- 208000000509 infertility Diseases 0.000 claims description 5
- 230000036512 infertility Effects 0.000 claims description 5
- 230000000977 initiatory effect Effects 0.000 claims description 5
- 208000001076 sarcopenia Diseases 0.000 claims description 5
- 208000019116 sleep disease Diseases 0.000 claims description 5
- 230000004936 stimulating effect Effects 0.000 claims description 5
- 230000001195 anabolic effect Effects 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 208000010392 Bone Fractures Diseases 0.000 claims description 3
- 206010006895 Cachexia Diseases 0.000 claims description 3
- 206010013883 Dwarfism Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 201000001322 T cell deficiency Diseases 0.000 claims description 3
- 208000027912 T-cell immunodeficiency Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 230000033228 biological regulation Effects 0.000 claims description 3
- 230000001925 catabolic effect Effects 0.000 claims description 3
- 238000002512 chemotherapy Methods 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 230000001419 dependent effect Effects 0.000 claims description 3
- 230000037406 food intake Effects 0.000 claims description 3
- 235000012631 food intake Nutrition 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 231100000535 infertility Toxicity 0.000 claims description 3
- 230000006651 lactation Effects 0.000 claims description 3
- 235000013336 milk Nutrition 0.000 claims description 3
- 239000008267 milk Substances 0.000 claims description 3
- 210000004080 milk Anatomy 0.000 claims description 3
- 210000003205 muscle Anatomy 0.000 claims description 3
- 230000000626 neurodegenerative effect Effects 0.000 claims description 3
- 208000003068 pituitary dwarfism Diseases 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 230000015355 regulation of circadian sleep/wake cycle, sleep Effects 0.000 claims description 3
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 2
- 201000006370 kidney failure Diseases 0.000 claims description 2
- 206010052428 Wound Diseases 0.000 claims 2
- 208000027418 Wounds and injury Diseases 0.000 claims 2
- 102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 description 156
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 155
- 241000282414 Homo sapiens Species 0.000 description 39
- 210000002381 plasma Anatomy 0.000 description 33
- 230000027455 binding Effects 0.000 description 32
- 241000700159 Rattus Species 0.000 description 29
- 210000002966 serum Anatomy 0.000 description 28
- 108090000765 processed proteins & peptides Proteins 0.000 description 26
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 25
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 25
- 238000011534 incubation Methods 0.000 description 24
- 241001465754 Metazoa Species 0.000 description 22
- 238000007920 subcutaneous administration Methods 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 230000017854 proteolysis Effects 0.000 description 17
- 101000825742 Homo sapiens Somatoliberin Proteins 0.000 description 16
- 102000045304 human GHRH Human genes 0.000 description 16
- 241000282472 Canis lupus familiaris Species 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- 230000004044 response Effects 0.000 description 15
- 108010056001 somatotropin releasing hormone (1-29) Proteins 0.000 description 15
- 235000001014 amino acid Nutrition 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 238000001990 intravenous administration Methods 0.000 description 13
- 241000282465 Canis Species 0.000 description 12
- 101000868151 Rattus norvegicus Somatotropin Proteins 0.000 description 12
- 230000001817 pituitary effect Effects 0.000 description 11
- WGWPRVFKDLAUQJ-MITYVQBRSA-N sermorelin Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)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@@H](C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C1=CC=C(O)C=C1 WGWPRVFKDLAUQJ-MITYVQBRSA-N 0.000 description 11
- 230000007958 sleep Effects 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 101000997535 Homo sapiens Growth hormone-releasing hormone receptor Proteins 0.000 description 7
- 230000002797 proteolythic effect Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 230000003285 pharmacodynamic effect Effects 0.000 description 6
- 238000003127 radioimmunoassay Methods 0.000 description 6
- 238000010254 subcutaneous injection Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- -1 but not limited to Substances 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 210000003016 hypothalamus Anatomy 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000007929 subcutaneous injection Substances 0.000 description 5
- QBEPNUQJQWDYKU-SZIVHBGHSA-N tesamorelin Chemical compound CC/C=C/CC(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)CC)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](C(C)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N QBEPNUQJQWDYKU-SZIVHBGHSA-N 0.000 description 5
- 108010053803 Sermorelin Proteins 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000000700 radioactive tracer Substances 0.000 description 4
- 210000001875 somatotroph Anatomy 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- 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 3
- 101001075374 Homo sapiens Gamma-glutamyl hydrolase Proteins 0.000 description 3
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 3
- 101000664737 Homo sapiens Somatotropin Proteins 0.000 description 3
- 206010062767 Hypophysitis Diseases 0.000 description 3
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- BVLCEKWPOSAKSZ-YQMCHIOTSA-N sermorelin acetate Chemical compound CC(O)=O.C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)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@@H](C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C1=CC=C(O)C=C1 BVLCEKWPOSAKSZ-YQMCHIOTSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010000521 Human Growth Hormone Proteins 0.000 description 2
- 239000000854 Human Growth Hormone Substances 0.000 description 2
- 102000002265 Human Growth Hormone Human genes 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- 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
- 239000004743 Polypropylene Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004198 anterior pituitary gland Anatomy 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000001851 biosynthetic effect Effects 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 208000021267 infertility disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 210000003635 pituitary gland Anatomy 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000000541 pulsatile effect Effects 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000003104 tissue culture media Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
- 125000000349 (Z)-3-carboxyprop-2-enoyl group Chemical group O=C([*])/C([H])=C([H])\C(O[H])=O 0.000 description 1
- ORVURRVCHHWGDK-UHFFFAOYSA-N 2-[[4-(3-chlorodiazirin-3-yl)benzoyl]amino]acetic acid Chemical compound C1=CC(C(=O)NCC(=O)O)=CC=C1C1(Cl)N=N1 ORVURRVCHHWGDK-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- PAPSMOYMQDWIOR-AVGNSLFASA-N Arg-Lys-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O PAPSMOYMQDWIOR-AVGNSLFASA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000034577 Benign intracranial hypertension Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010018265 Gigantism Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010056438 Growth hormone deficiency Diseases 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 208000018127 Idiopathic intracranial hypertension Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 208000006302 Laron syndrome Diseases 0.000 description 1
- IRMLZWSRWSGTOP-CIUDSAMLSA-N Leu-Ser-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O IRMLZWSRWSGTOP-CIUDSAMLSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- WEDDFMCSUNNZJR-WDSKDSINSA-N Met-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(O)=O WEDDFMCSUNNZJR-WDSKDSINSA-N 0.000 description 1
- 108010016076 Octreotide Proteins 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- JHSRGEODDALISP-XVSYOHENSA-N Phe-Thr-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O JHSRGEODDALISP-XVSYOHENSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- 101001075370 Rattus norvegicus Gamma-glutamyl hydrolase Proteins 0.000 description 1
- 101000997546 Rattus norvegicus Growth hormone-releasing hormone receptor Proteins 0.000 description 1
- 101000687509 Rattus norvegicus Prolactin Proteins 0.000 description 1
- 241001021910 Rhizomys sumatrensis Species 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000010340 Sleep Deprivation Diseases 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003329 adenohypophysis hormone Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000004479 aerosol dispenser Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000003295 arcuate nucleus Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 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 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- QLBHNVFOQLIYTH-UHFFFAOYSA-L dipotassium;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [K+].[K+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O QLBHNVFOQLIYTH-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 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 1
- 206010016165 failure to thrive Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 231100000001 growth retardation Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 208000001381 pseudotumor cerebri Diseases 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 230000008454 sleep-wake cycle Effects 0.000 description 1
- 230000037322 slow-wave sleep Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 229940075620 somatostatin analogue Drugs 0.000 description 1
- 108700031632 somatrem Proteins 0.000 description 1
- 229960003259 somatrem Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000002483 superagonistic effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 210000000221 suprachiasmatic nucleus Anatomy 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- 230000001173 tumoral effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Rheumatology (AREA)
- Toxicology (AREA)
- Neurosurgery (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Diabetes (AREA)
- Wood Science & Technology (AREA)
- Reproductive Health (AREA)
- Oncology (AREA)
- Biotechnology (AREA)
- Obesity (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41134002P | 2002-09-18 | 2002-09-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200502221B true ZA200502221B (en) | 2006-08-30 |
Family
ID=32030666
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200502221A ZA200502221B (en) | 2002-09-18 | 2005-03-16 | GHRH analogues |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US20060128615A1 (zh) |
| EP (1) | EP1539959A2 (zh) |
| JP (1) | JP2006504694A (zh) |
| KR (1) | KR20050071498A (zh) |
| CN (1) | CN1688696A (zh) |
| BR (1) | BR0314619A (zh) |
| CA (1) | CA2496687A1 (zh) |
| MX (1) | MXPA05002991A (zh) |
| NO (1) | NO20051804L (zh) |
| NZ (1) | NZ539218A (zh) |
| RU (1) | RU2005111253A (zh) |
| WO (1) | WO2004027064A2 (zh) |
| ZA (1) | ZA200502221B (zh) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008095063A1 (en) | 2007-01-31 | 2008-08-07 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| EP2508531B1 (en) | 2007-03-28 | 2016-10-19 | President and Fellows of Harvard College | Stitched polypeptides |
| CN101678083A (zh) * | 2007-04-04 | 2010-03-24 | 瑟瑞技术公司 | Ghrh分子的药物制剂 |
| US20090088380A1 (en) * | 2007-07-12 | 2009-04-02 | Pierrette Gaudreau | Ghrh analogs and therapeutic uses thereof |
| WO2010121351A1 (en) * | 2009-04-20 | 2010-10-28 | Theratechnologies Inc. | Use of (hexenoyl trans-3)hgrf(1-44)nh2 and ritonavir in combination therapy |
| US20100267636A1 (en) * | 2009-04-20 | 2010-10-21 | Theratechnologies Inc. | Use of cytochrome p450-metabolized drugs and grf molecules in combination therapy |
| WO2011153491A2 (en) | 2010-06-03 | 2011-12-08 | University Of Miami | Agonists of growth hormone releasing hormone as effectors for survival and proliferation of pancreatic islets |
| SI2603600T1 (sl) | 2010-08-13 | 2019-04-30 | Aileron Therapeutics, Inc. | Peptidomimetični makrocikli |
| WO2012037519A2 (en) * | 2010-09-16 | 2012-03-22 | University Of Miami | Acceleration of wound healing by growth hormone releasing hormone and its agonists |
| KR20140027284A (ko) | 2011-04-21 | 2014-03-06 | 쎄러테크놀로지스 인코포레이티드 | 성장 호르몬 방출 인자(grf) 유사체 및 이의 용도 |
| AU2012326026B2 (en) | 2011-10-18 | 2017-04-13 | Aileron Therapeutics, Inc. | Peptidomimetic macrocyles |
| US9079974B2 (en) | 2011-12-21 | 2015-07-14 | The University Of Miami | GH-RH analogs with potent agonistic effects |
| CN112500466B (zh) | 2012-02-15 | 2022-05-03 | 艾瑞朗医疗公司 | 拟肽大环化合物 |
| WO2013123267A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| WO2013190520A2 (en) | 2012-06-22 | 2013-12-27 | The General Hospital Corporation | Gh-releasing agents in the treatment of vascular stenosis and associated conditions |
| AU2013337388B2 (en) | 2012-11-01 | 2018-08-02 | Aileron Therapeutics, Inc. | Disubstituted amino acids and methods of preparation and use thereof |
| EP2934565B1 (en) | 2012-12-21 | 2019-03-13 | University of Miami | Ghrh agonists for the treatment of ischemic disorders |
| WO2014100816A2 (en) | 2012-12-21 | 2014-06-26 | University Of Miami | Ghrh agonists for islet cell transplantation and function and the treatment of diabetes |
| US20150174207A1 (en) * | 2013-12-24 | 2015-06-25 | University Of Miami | Methods for treating cancer with ghrh agonists |
| CN105198966B (zh) * | 2014-06-26 | 2019-06-21 | 中国人民解放军军事医学科学院毒物药物研究所 | GnRH类似物-细胞毒分子缀合物、其制备方法及用途 |
| BR112017005598A2 (pt) | 2014-09-24 | 2017-12-12 | Aileron Therapeutics Inc | macrociclos peptidomiméticos e usos dos mesmos |
| CN104558150B (zh) * | 2014-11-04 | 2017-12-15 | 广东药学院 | 一类生长激素释放激素类似肽及其在制备治疗不孕不育药物中的应用 |
| KR20170129879A (ko) | 2015-03-20 | 2017-11-27 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티드모방 거대고리 및 이의 용도 |
| US9988428B2 (en) | 2016-04-19 | 2018-06-05 | Griffon Pharmaceuticals Inc. | Pegylated bioactive peptides and uses thereof |
| CN111407884B (zh) * | 2019-06-24 | 2021-12-07 | 浙江大学 | 促生长激素释放激素激动剂ghrh-a在制备抗衰老药物中的用途 |
| CN111533800B (zh) * | 2020-03-18 | 2021-08-31 | 浙江湖州纳福生物医药有限公司 | 新型生长激素释放激素类似肽改构和二聚体化制备及其应用 |
Family Cites Families (115)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US652047A (en) * | 1899-09-23 | 1900-06-19 | Nelson T Shields | Artificial tooth. |
| US4411890A (en) * | 1981-04-14 | 1983-10-25 | Beckman Instruments, Inc. | Synthetic peptides having pituitary growth hormone releasing activity |
| US3862925A (en) * | 1973-07-05 | 1975-01-28 | American Home Prod | Preparation of somatotropin release inhibiting factor and intermediates therefor |
| US3842067A (en) * | 1973-07-27 | 1974-10-15 | American Home Prod | Synthesis of(des-asn5)-srif and intermediates |
| US4301066A (en) * | 1980-05-08 | 1981-11-17 | American Home Products Corp. | Preparation of (D-Trp 6)-LH-RH via the heptapeptide H-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2 |
| US4439356A (en) * | 1981-03-03 | 1984-03-27 | Syva Company | Unsymmetrical fluorescein derivatives |
| US4517181A (en) * | 1982-09-15 | 1985-05-14 | The Salk Institute For Biological Studies | Mammalian PGRF |
| US4595676A (en) * | 1983-04-26 | 1986-06-17 | The Salk Institute For Biological Studies | Rat hypothalamic GRF |
| US4529595A (en) * | 1983-01-13 | 1985-07-16 | The Salk Institute For Biological Studies | GRF Analogs |
| US4563352A (en) * | 1982-10-04 | 1986-01-07 | The Salk Institute For Biological Studies | Human pancreatic GRF |
| US4518586A (en) * | 1983-01-13 | 1985-05-21 | The Salk Institute For Biological Studies | GRF Analogs III |
| US4628043A (en) * | 1983-04-26 | 1986-12-09 | The Salk Institute For Biological Studies | Hypothalamic GRF agonists |
| US4605643A (en) * | 1984-03-02 | 1986-08-12 | The Salk Institute For Biological Studies | Ovine GRF |
| US4585756A (en) * | 1983-10-12 | 1986-04-29 | The Salk Institute For Biological Studies | Bovine GRF |
| US4610976A (en) * | 1983-08-29 | 1986-09-09 | The Salk Institute For Biological Studies | Porcine GRF |
| US4626523A (en) * | 1983-09-13 | 1986-12-02 | The Salk Institute For Biological Studies | GRF analogs II |
| US4528190A (en) * | 1983-10-25 | 1985-07-09 | The Salk Institute For Biological Studies | GRF Analogs IV |
| US4622312A (en) * | 1984-09-24 | 1986-11-11 | Hoffmann-La Roche Inc. | Growth hormone releasing factor analogs |
| EP0189673B1 (en) * | 1984-12-24 | 1990-09-26 | Sumitomo Pharmaceuticals Company, Limited | Stable growth hormone releasing factor preparation |
| US4734399A (en) * | 1985-08-06 | 1988-03-29 | Hoffmann-La Roche Inc. | Growth hormone releasing factor analogs |
| US4689318A (en) * | 1985-08-29 | 1987-08-25 | The Salk Institute For Biological Studies | GRF analogs |
| US4843064A (en) * | 1987-01-13 | 1989-06-27 | The Salk Institute For Biological Studies | GRF analogs V |
| US4784987A (en) * | 1987-01-13 | 1988-11-15 | The Salk Institute For Biological Studies | GRF analogs VI |
| US5877277A (en) * | 1987-09-24 | 1999-03-02 | Biomeasure, Inc. | Octapeptide bombesin analogs |
| US5756458A (en) * | 1989-06-16 | 1998-05-26 | Pharmacia & Upjohn Company | Stabilized potent GRF analogs |
| US5137872A (en) * | 1989-09-18 | 1992-08-11 | Pitman-Moore, Inc. | Growth hormone-releasing factor analogs |
| WO1992018531A1 (en) * | 1991-04-09 | 1992-10-29 | F. Hoffmann-La Roche Ag | Growth hormone releasing factor analogs |
| US5262519A (en) * | 1991-05-15 | 1993-11-16 | The Salk Institute For Biological Studies | GRF analogs XI |
| US6916489B2 (en) * | 1992-06-15 | 2005-07-12 | Emisphere Technologies, Inc. | Active agent transport systems |
| US6461643B2 (en) * | 1993-04-22 | 2002-10-08 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
| US20010003001A1 (en) * | 1993-04-22 | 2001-06-07 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| SE9301667D0 (sv) * | 1993-05-14 | 1993-05-14 | Kabi Pharmacia Ab | New use |
| US6297212B1 (en) * | 1994-05-31 | 2001-10-02 | Gregory M. Fahy | Growth hormone therapy and related methods and pharmaceutical compositions |
| US5837276A (en) * | 1994-09-02 | 1998-11-17 | Delab | Apparatus for the delivery of elongate solid drug compositions |
| CA2158782C (en) * | 1994-09-23 | 2010-01-12 | Pierrette Gaudreau | Marker for growth hormone-releasing factor receptors |
| US20020111461A1 (en) * | 1999-05-21 | 2002-08-15 | Todd C. Somers | Low molecular weight peptidomimetic growth hormone secretagogues |
| US6458764B1 (en) * | 1995-05-26 | 2002-10-01 | Theratechnologies Inc. | GRF analogs with increased biological potency |
| IT1285405B1 (it) * | 1995-06-06 | 1998-06-03 | Alza Corp | Modificazione di farmaci polipeptidici per accrescere il flusso per elettrotrasporto. |
| TW432073B (en) * | 1995-12-28 | 2001-05-01 | Pfizer | Pyrazolopyridine compounds |
| KR100445087B1 (ko) * | 1996-01-11 | 2004-10-15 | 파마시아 앤드 업존 캄파니 | 수성서방성제제 |
| CA2250219C (en) * | 1996-03-28 | 2008-10-07 | Hayat Onyuksel | Materials and methods for making improved liposome compositions |
| CA2255865C (en) * | 1996-05-24 | 2008-10-14 | The Regents Of The University Of Minnesota | Synthesis of soluble beta-sheet forming peptides |
| DK1007080T3 (da) * | 1996-08-30 | 2007-07-30 | Peptech Ltd | Formulering til vedvarende frigivelse af peptidagonister og analoger af GnRH |
| US6420518B1 (en) * | 1997-04-04 | 2002-07-16 | Genetech, Inc. | Insulin-like growth factor agonist molecules |
| US6121416A (en) * | 1997-04-04 | 2000-09-19 | Genentech, Inc. | Insulin-like growth factor agonist molecules |
| AR012448A1 (es) * | 1997-04-18 | 2000-10-18 | Ipsen Pharma Biotech | Composicion en forma de microcapsulas o de implantes que comprende un excipiente biodegradable, polimero o co-polimero, o una mezcla de talesexcipientes, y una sustancia activa o una mezcla de sustancias activas, procedimiento para la preparacion de una sustancia soluble en agua de elevada |
| JP3514774B2 (ja) * | 1997-06-25 | 2004-03-31 | ファイザー・インク | 成長ホルモン分泌促進薬としてのジペプチド誘導体 |
| UA64751C2 (uk) * | 1997-06-25 | 2004-03-15 | Пфайзер Продактс Інк. | Спосіб лікування інсулінової толерантності речовинами, які посилюють секрецію гормону росту (варіанти) та фармацевтична композиція (варіанти) |
| EP0988388A2 (en) * | 1997-07-24 | 2000-03-29 | Valentis Inc. | Ghrh expression system and methods of use |
| AUPO930697A0 (en) * | 1997-09-19 | 1997-10-09 | Walter And Eliza Hall Institute Of Medical Research, The | Catalytic antibodies and a method of producing same |
| GB9723955D0 (en) * | 1997-11-14 | 1998-01-07 | Generic Biolog Limited | Improvements in or relating to detection of molecules in samples |
| EP0922446A1 (en) * | 1997-12-03 | 1999-06-16 | Applied Research Systems Ars Holding N.V. | Solution-phase site-specific preparation of GRF-PEG conjugates |
| EP1052994A2 (en) * | 1998-02-02 | 2000-11-22 | Trustees Of Tufts College | Use of dipeptidylpetidase inhibitors to regulate glucose metabolism |
| US20030167531A1 (en) * | 1998-07-10 | 2003-09-04 | Russell Douglas A. | Expression and purification of bioactive, authentic polypeptides from plants |
| US6512162B2 (en) * | 1998-07-10 | 2003-01-28 | Calgene Llc | Expression of eukaryotic peptides in plant plastids |
| US6057422A (en) * | 1998-11-25 | 2000-05-02 | The Administrators Of The Tulane Educational Fund | Antagonistic analogs of GH-RH inhibiting IGF-I and -II |
| US6696063B1 (en) * | 1998-12-30 | 2004-02-24 | Applied Research Systems Ars Holding N.V. | Treatment of HIV-associated dysmorphia/dysmetabolic syndrome (HADDS) with or without lipodystrophy |
| DE60042550D1 (de) * | 1999-01-06 | 2009-08-27 | Genentech Inc | Mutierte varianten des insulin-ähnlichen wachstumsfaktor i (igf-i) |
| WO2000047203A1 (en) * | 1999-02-12 | 2000-08-17 | Mqs, Inc. | Formulation and system for intra-oral delivery of pharmaceutical agents |
| US6759393B1 (en) * | 1999-04-12 | 2004-07-06 | Pfizer Inc. | Growth hormone and growth hormone releasing hormone compositions |
| US6437101B1 (en) * | 1999-05-07 | 2002-08-20 | Akzo Nobel N.V. | Methods for protein purification using aqueous two-phase extraction |
| US6268178B1 (en) * | 1999-05-25 | 2001-07-31 | Phage Biotechnology Corp. | Phage-dependent super-production of biologically active protein and peptides |
| US7078514B1 (en) * | 1999-06-12 | 2006-07-18 | Michael O. Thorner | Chicken growth hormone releasing hormone receptor |
| GB9915200D0 (en) * | 1999-06-29 | 1999-09-01 | Janssen Pharmaceutica Nv | Neurotrophic factor receptor |
| EP1064934A1 (en) * | 1999-06-30 | 2001-01-03 | Applied Research Systems ARS Holding N.V. | GRF-containing lyophilized pharmaceutical composition |
| DK1795598T3 (da) * | 1999-07-23 | 2010-02-01 | Kenji Kangawa | Hidtil ukendte peptider |
| US20040192593A1 (en) * | 1999-07-26 | 2004-09-30 | Baylor College Of Medicine | Protease resistant ti-growth hormone releasing hormone |
| CN1635898A (zh) * | 1999-07-26 | 2005-07-06 | 贝勒医学院 | 超级活性的猪生长激素释放激素类似物 |
| KR100345214B1 (ko) * | 1999-08-17 | 2002-07-25 | 이강춘 | 생체적합성 고분자가 수식된 펩타이드의 비점막 전달 |
| WO2001032200A1 (en) * | 1999-11-03 | 2001-05-10 | Novo Nordisk A/S | Use of a growth hormone or a growth hormone secretagogue for appetite-suppression or induction of satiety |
| ATE304373T1 (de) * | 1999-12-28 | 2005-09-15 | Kaken Pharma Co Ltd | Nervenschutzmittel |
| US6866851B1 (en) * | 1999-12-28 | 2005-03-15 | Washington University | GFRα1-RET specific agonists and methods therefor |
| US20010020012A1 (en) * | 2000-02-01 | 2001-09-06 | Andersen Maibritt Bansholm | Use of compounds for the regulation of food intake |
| AU2001249456A1 (en) * | 2000-03-24 | 2001-10-08 | Millennium Pharmaceuticals, Inc. | 46743 and 27417, novel human acyltransferase family members and uses therefor |
| US7834141B1 (en) * | 2000-03-31 | 2010-11-16 | Theresa Siler-Khodr | Non-mammalian GnRH analogs and uses thereof in tumor cell growth regulation and cancer therapy |
| AU2001266557A1 (en) * | 2000-04-12 | 2001-10-23 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| CA2380423A1 (en) * | 2000-05-17 | 2001-11-22 | Bionebraska, Inc. | Peptide pharmaceutical formulations |
| WO2001092292A2 (en) * | 2000-05-30 | 2001-12-06 | Merck & Co., Inc. | Ghrelin analogs |
| BR0113178A (pt) * | 2000-08-02 | 2004-04-06 | Theratechnologies Inc | Peptìdeos biológicos modificados com potência aumentada |
| WO2002028437A1 (en) * | 2000-10-05 | 2002-04-11 | Ares Trading S.A. | Regioselective liquid phase pegylation |
| US6750194B1 (en) * | 2000-10-23 | 2004-06-15 | The Procter & Gamble Company | Methods of identifying compounds for regulating muscle mass or function using vasoactive intestinal peptide receptors |
| US20030083299A1 (en) * | 2000-11-04 | 2003-05-01 | Ferguson Ian A. | Non-invasive delivery of polypeptides through the blood-brain barrier |
| WO2003049761A1 (en) * | 2000-12-08 | 2003-06-19 | Neuronz Limited | Use of insuline-like growth factor-i for promoting remyelination of axons |
| US20030074679A1 (en) * | 2000-12-12 | 2003-04-17 | Schwartz Robert J. | Administration of nucleic acid sequence to female animal to enhance growth in offspring |
| US20020091090A1 (en) * | 2000-12-28 | 2002-07-11 | Cole Bridget M. | Somatostatin antagonists and agonists |
| CU23157A1 (es) * | 2001-01-03 | 2006-07-18 | Ct Ingenieria Genetica Biotech | COMPOSICION FARMACéUTICA PARA EL TRATAMIENTO DEL DANO TISULAR DEBIDO A FALTA DE IRRIGACION SANGUINEA ARTERIAL |
| US7264810B2 (en) * | 2001-01-19 | 2007-09-04 | Cytos Biotechnology Ag | Molecular antigen array |
| JP2004520395A (ja) * | 2001-02-02 | 2004-07-08 | コンジュケム，インコーポレーテッド | 長期持続性成長ホルモン放出因子誘導体 |
| FR2821359B1 (fr) * | 2001-02-27 | 2003-05-09 | Sod Conseils Rech Applic | L'heterocarpine, une proteine fixant le ghrh humain |
| US6890905B2 (en) * | 2001-04-02 | 2005-05-10 | Prosidion Limited | Methods for improving islet signaling in diabetes mellitus and for its prevention |
| EP1385879A4 (en) * | 2001-05-10 | 2005-02-02 | Univ Queensland | DIAGNOSIS AND THERAPY OF CANCER OF REPRODUCTIVE ORGANS |
| EP1260229A3 (en) * | 2001-05-18 | 2002-12-11 | Sumitomo Pharmaceuticals Company, Limited | Anti-autoimmune composition comprising inhibitors of growth hormone-releasing factor activity |
| US6858580B2 (en) * | 2001-06-04 | 2005-02-22 | Nobex Corporation | Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| IL159048A0 (en) * | 2001-06-21 | 2004-05-12 | Genentech Inc | Sustained release formulation |
| US20030157717A1 (en) * | 2001-09-07 | 2003-08-21 | Baylor College Of Medicine Texas Medical Center | Linear DNA fragments for gene expression |
| CN100417419C (zh) * | 2001-10-26 | 2008-09-10 | 贝勒医学院 | 改变个体的瘦体重和骨特性的组合物和方法 |
| PL195917B1 (pl) * | 2001-10-31 | 2007-11-30 | Inst Farmaceutyczny | Nowe peptydy - analogi ludzkiego hormonu uwalniającego hormon wzrostu |
| US7297794B2 (en) * | 2001-11-13 | 2007-11-20 | Emisphere Technologies, Inc. | Phenoxy amine compounds and compositions for delivering active agents |
| WO2003047624A1 (en) * | 2001-12-07 | 2003-06-12 | Kaken Pharmaceutical Co., Ltd. | Cell migration inhibitor |
| MXPA04007638A (es) * | 2002-02-07 | 2004-12-06 | Baylor College Medicine | Desarrollo modificado de la glandula pituitaria en productos de madres animales prenadas, tratadas con terapia de hormona liberadora de hormona del crecimiento. |
| CA2476427A1 (en) * | 2002-02-20 | 2003-08-28 | Regents Of The University Of Minnesota | Partial peptide mimetics and methods |
| BR0308137A (pt) * | 2002-03-04 | 2005-01-04 | Sod Conseils Rech Applic | Formulações de droga de liberação constante contendo um peptìdeo veìculo |
| EP1493747B1 (en) * | 2002-04-11 | 2012-12-19 | Daiichi Sankyo Company, Limited | Process for producing modified peptide |
| WO2003086272A2 (en) * | 2002-04-16 | 2003-10-23 | Kamada Ltd. | Ultrapure transferrin for pharmaceutical compositions |
| WO2003097083A1 (fr) * | 2002-05-21 | 2003-11-27 | Daiichi Suntory Pharma Co.,Ltd. | Compositions medicinales contenant de la ghreline |
| EP1532261B1 (en) * | 2002-05-24 | 2010-02-10 | Medtronic, Inc. | Methods and dna constructs for high yield production of polypeptides |
| US20040014645A1 (en) * | 2002-05-28 | 2004-01-22 | Advisys, Inc. | Increased delivery of a nucleic acid construct in vivo by the poly-L-glutamate ("PLG") system |
| ES2422881T3 (es) * | 2002-06-20 | 2013-09-16 | Augustinus Bader | Uso de eritropoyetina para la regeneración de tejido in vivo |
| DE60336736D1 (de) * | 2002-07-16 | 2011-05-26 | VGX Pharmaceuticals LLC | Codon-optimierte synthetische plasmide |
| BR0311800A (pt) * | 2002-07-19 | 2005-03-22 | Cytos Biotechnology Ag | Conjugados ghrelina-veìculo |
| TWI331922B (en) * | 2002-08-09 | 2010-10-21 | Ipsen Pharma Sas | Growth hormone releasing peptides |
| EP1407779A1 (en) * | 2002-10-10 | 2004-04-14 | Gastrotech A/S | Use of ghrelin for treating low body weight and body fat in gastrectomized individuals |
| EP1628676A1 (en) * | 2003-05-29 | 2006-03-01 | Theratechnologies Inc. | Grf analog compositions and their use |
| MXPA06000954A (es) * | 2003-07-29 | 2006-05-04 | Ares Trading Sa | Uso de hormona del crecimiento humano en atrofia de multiples sistemas. |
| US20050063937A1 (en) * | 2003-09-16 | 2005-03-24 | Cheng Li | Multiple-arm peptide compounds, methods of manufacture and use in therapy |
-
2003
- 2003-09-17 KR KR1020057004781A patent/KR20050071498A/ko not_active Application Discontinuation
- 2003-09-17 RU RU2005111253/13A patent/RU2005111253A/ru not_active Application Discontinuation
- 2003-09-17 MX MXPA05002991A patent/MXPA05002991A/es unknown
- 2003-09-17 BR BR0314619-7A patent/BR0314619A/pt not_active IP Right Cessation
- 2003-09-17 WO PCT/CA2003/001418 patent/WO2004027064A2/en active Application Filing
- 2003-09-17 EP EP03750194A patent/EP1539959A2/en not_active Withdrawn
- 2003-09-17 CA CA002496687A patent/CA2496687A1/en not_active Abandoned
- 2003-09-17 CN CNA038222914A patent/CN1688696A/zh active Pending
- 2003-09-17 NZ NZ539218A patent/NZ539218A/en unknown
- 2003-09-17 JP JP2004536729A patent/JP2006504694A/ja active Pending
- 2003-09-17 US US10/527,598 patent/US20060128615A1/en not_active Abandoned
-
2005
- 2005-03-16 ZA ZA200502221A patent/ZA200502221B/en unknown
- 2005-04-13 NO NO20051804A patent/NO20051804L/no not_active Application Discontinuation
-
2007
- 2007-06-01 US US11/809,596 patent/US20090023646A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR20050071498A (ko) | 2005-07-07 |
| RU2005111253A (ru) | 2005-11-20 |
| NZ539218A (en) | 2008-03-28 |
| WO2004027064A2 (en) | 2004-04-01 |
| BR0314619A (pt) | 2005-08-02 |
| MXPA05002991A (es) | 2005-10-05 |
| CA2496687A1 (en) | 2004-04-01 |
| WO2004027064A3 (en) | 2004-11-18 |
| AU2003269631A1 (en) | 2004-04-08 |
| JP2006504694A (ja) | 2006-02-09 |
| US20090023646A1 (en) | 2009-01-22 |
| CN1688696A (zh) | 2005-10-26 |
| NO20051804L (no) | 2005-04-13 |
| EP1539959A2 (en) | 2005-06-15 |
| US20060128615A1 (en) | 2006-06-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20090023646A1 (en) | GHRH analogues | |
| AU2019311000B2 (en) | GIP/GLP1 co-agonist compounds | |
| DE69935229T2 (de) | Neue antidiabetische peptide | |
| Thomas et al. | Pure brain-derived acidic fibroblast growth factor is a potent angiogenic vascular endothelial cell mitogen with sequence homology to interleukin 1. | |
| US4880778A (en) | Combinations having synergistic growth hormone releasing activity and methods for use thereof | |
| EP0489089B1 (en) | Therapeutic peptides | |
| WO1990003980A1 (en) | Therapeutic peptides | |
| WO1989002897A1 (en) | Therapeutic peptides | |
| KR101228229B1 (ko) | 성장 호르몬 분비 촉진물질 및 그의 용도 | |
| AU651976B2 (en) | Novel synthetic GRF analogs | |
| CA2221148C (en) | Muscle trophic factor | |
| AU3338400A (en) | Treatment of bone disorders with adrenomedullin or adrenomedullin agonists | |
| SK7252001A3 (en) | Antagonistic analogs of gh-rh inhibiting igf-i and -ii | |
| EP1011716B1 (en) | Neuromedin b receptor antagonists | |
| JP2002522355A (ja) | 新規な混合アミリン活性化合物 | |
| AU2003269631B2 (en) | GHRH analogues | |
| AU617426B2 (en) | Growth hormone releasing factor analogs | |
| JP2004002331A (ja) | 肝臓癌の治療 | |
| DE69734349T2 (de) | Behandlung von knochenleiden mit adrenomedullin | |
| Lefrançois et al. | Identification of receptor-binding pharmacophores of growth-hormone-releasing factor in rat adenopituitary | |
| Pless | Chemical Structure—Pharmacological Profile of Sandostatin® | |
| Weir et al. | Adenylate cyclase-stimulating, bone-resorbing and B TGF-like activities in canine apocrine cell adenocarcinoma of the anal sac | |
| Kovàcs et al. | New Gaba-containing analogues of human Growth Hormone Releasing Hormene (1–30)-amide: II. Detailed in vivo biological examinations | |
| AU622123C (en) | Therapeutic peptides | |
| MXPA97009880A (en) | Apet regulatory compositions |