| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-02-19 16:04:28 |
| Primary Accession Number |
DB00506 |
| Secondary Accession Number |
|
| Name |
Norgestrel |
| Drug Type |
|
| Description |
A synthetic progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [PubChem] |
| Synonyms |
Not Available |
| Brand Names |
- Alesse
- Alpha-Norgestrel
- Component of Lo/Ovral
- Component of Ovral
- DL-Norgestrel
- LD Norgestrel
- Ld Norgestrel [French]
- Lo/Ovral
- Logynon
- Methylnorethindrone
- Microgynon
- Microlut
- Monovar
- NOG
- Neogest
- Norgeston
- Norgestrel [Progestins]
- Norgestrel [Usan:Ban:Inn:Jan]
- Norgestrelum [INN-Latin]
- Ovral
- Ovran
- Postinor
- Stediril
- Tetragynon
- Trinordiol
|
| Brand Mixtures |
- Lo-Femenal 21 Tablets (ethinyl estradiol + norgestrel)
- Ovral 21 Tablets (ethinyl estradiol + norgestrel)
- Ovral 28 Tablets (ethinyl estradiol + norgestrel)
|
| Chemical IUPAC Name |
(8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one |
| Chemical Formula |
C21H28O2 |
| Chemical Structure |
 |
| CAS Registry Number |
6533-00-2 |
| InChI Identifier |
InChI=1/C21H28O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1 |
| InChI Key |
WWYNJERNGUHSAO-XUDSTZEEBP |
| KEGG Drug |
D00954  |
| KEGG Compound |
C08153  |
| PubChem Compound |
13109  |
| PubChem Substance |
7848017  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA450656  |
| HET ID |
NOG  |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
Not Available |
| RxList Link |
http://www.rxlist.com/cgi/generic/norgeth.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Norgestrel  |
| FDA Label |
Not Available |
| Material Safety Data Sheet (MSDS) |
Not Available |
| Synthesis Reference |
G. A. Smith, H. Smith, U.S. Pat. 3,959,322 (1976) |
| Average Molecular Weight |
312.4458 |
| Monoisotopic Molecular Weight |
312.2089 |
| State |
Solid |
| Melting Point |
206oC |
| Experimental Water Solubility |
0.00173 mg/mL [PINSUWAN,S et al. (1997)]
Source: PhysProp
|
| Predicted Water Solubility |
5.83e-03 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
3.8
Source: PhysProp
|
| Predicted LogP |
3.25
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-4.73
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
CC[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@H]34)[C@@H]1CC[C@@]2(O)C#C |
| Canonical SMILES |
CCC12CCC3C(CCC4=CC(=O)CCC34)C1CCC2(O)C#C |
| Drug Category |
- Contraceptive Agents, Female
- Contraceptives
- Contraceptives, Oral, Synthetic
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
Used as an oral contraceptive to prevent pregnancy |
| Pharmacology |
Norgestrel is used as a female contraceptive. Norgestrel is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Norgestrel tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries. |
| Mechanism of Action |
Norgestrel binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like Norgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. |
| Absorption |
65% |
| Toxicity |
Nausea, vomiting, and drowsiness/fatigue; Withdrawal bleeding; LD50=mg/kg (orally in rat) |
| Protein Binding |
Norgestrel-binding protein in the plasma appeared to be a protein different from human serum albumin, corticosteroid-binding globulin and sex-steroid-binding protein. High binding (>95%). |
| Biotransformation |
Hepatic |
| Half Life |
5-14 hours |
| Dosage Forms |
| Form |
Route |
| Insert, extended release |
Intrauterine |
| Tablet |
Oral |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
Not Available
|
| Food Interactions |
- Avoid alcohol.
- Avoid excessive quantities of coffee or tea (Caffeine).
- Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
- Take at the same time everyday.
- Take with food.
|
| Pathways |
Not Available
|
| General References |
- Drugs.com

- Wikipedia

- RxList

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 2C19 (CYP2C19)
- Cytochrome P450 3A4 (CYP3A4)
|
| Targets |
- Estrogen receptor
- Alpha-1A adrenergic receptor
- Progesterone receptor
|
|
Drug Target 1
[top]
|
| Target 1 ID |
136 |
| Target 1 Name |
Estrogen receptor |
| Target 1 Synonyms |
- ER
- ER-alpha
- Estradiol receptor
|
| Target 1 Gene Name |
ESR1 |
| Target 1 Protein Sequence |
>Estrogen receptor
MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAY
EFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPF
LQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAK
ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQAC
RLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKR
SKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINW
AKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEG
MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLD
KITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLL
LEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
|
| Target 1 Number of Residues |
604 |
| Target 1 Molecular Weight |
66217 |
| Target 1 Theoretical pI |
8.14 |
| Target 1 GO Classification |
|
Function
|
ion binding
cation binding
transition metal ion binding
zinc ion binding
steroid binding
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity |
|
Process
|
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent |
|
Component
|
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus |
|
| Target 1 General Function |
Involved in transcription factor activity |
| Target 1 Specific Function |
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues |
| Target 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
31234  |
| Target 1 UniProtKB/Swiss-Prot ID |
P03372  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
ESR1_HUMAN  |
| Target 1 PDB ID |
1R5K  |
| Target 1 PDB File |
Show |
| Target 1 3D Structure |
|
| Target 1 Cellular Location |
|
| Target 1 Gene Sequence |
>1788 bp
ATGACCATGACCCTCCACACCAAAGCATCTGGGATGGCCCTACTGCATCAGATCCAAGGG
AACGAGCTGGAGCCCCTGAACCGTCCGCAGCTCAAGATCCCCCTGGAGCGGCCCCTGGGC
GAGGTGTACCTGGACAGCAGCAAGCCCGCCGTGTACAACTACCCCGAGGGCGCCGCCTAC
GAGTTCAACGCCGCGGCCGCCGCCAACGCGCAGGTCTACGGTCAGACCGGCCTCCCCTAC
GGCCCCGGGTCTGAGGCTGCGGCGTTCGGCTCCAACGGCCTGGGGGGTTTCCCCCCACTC
AACAGCGTGTCTCCGAGCCCGCTGATGCTACTGCACCCGCCGCCGCAGCTGTCGCCTTTC
CTGCAGCCCCACGGCCAGCAGGTGCCCTACTACCTGGAGAACGAGCCCAGCGGCTACACG
GTGCGCGAGGCCGGCCCGCCGGCATTCTACAGGCCAAATTCAGATAATCGACGCCAGGGT
GGCAGAGAAAGATTGGCCAGTACCAATGACAAGGGAAGTATGGCTATGGAATCTGCCAAG
GAGACTCGCTACTGTGCAGTGTGCAATGACTATGCTTCAGGCTACCATTATGGAGTCTGG
TCCTGTGAGGGCTGCAAGGCCTTCTTCAAGAGAAGTATTCAAGGACATAACGACTATATG
TGTCCAGCCACCAACCAGTGCACCATTGATAAAAACAGGAGGAAGAGCTGCCAGGCCTGC
CGGCTCCGCAAATGCTACGAAGTGGGAATGATGAAAGGTGGGATACGAAAAGACCGAAGA
GGAGGGAGAATGTTGAAACACAAGCGCCAGAGAGATGATGGGGAGGGCAGGGGTGAAGTG
GGGTCTGCTGGAGACATGAGAGCTGCCAACCTTTGGCCAAGCCCGCTCATGATCAAACGC
TCTAAGAAGAACAGCCTGGCCTTGTCCCTGACGGCCGACCAGATGGTCAGTGCCTTGTTG
GATGCTGAGCCCCCCATACTCTATTCCGAGTATGATCCTACCAGACCCTTCAGTGAAGCT
TCGATGATGGGCTTACTGACCAACCTGGCAGACAGGGAGCTGGTTCACATGATCAACTGG
GCGAAGAGGGTGCCAGGCTTTGTGGATTTGACCCTCCATGATCAGGTCCACCTTCTAGAA
TGTGCCTGGCTAGAGATCCTGATGATTGGTCTCGTCTGGCGCTCCATGGAGCACCCAGTG
AAGCTACTGTTTGCTCCTAACTTGCTCTTGGACAGGAACCAGGGAAAATGTGTAGAGGGC
ATGGTGGAGATCTTCGACATGCTGCTGGCTACATCATCTCGGTTCCGCATGATGAATCTG
CAGGGAGAGGAGTTTGTGTGCCTCAAATCTATTATTTTGCTTAATTCTGGAGTGTACACA
TTTCTGTCCAGCACCCTGAAGTCTCTGGAAGAGAAGGACCATATCCACCGAGTCCTGGAC
AAGATCACAGACACTTTGATCCACCTGATGGCCAAGGCAGGCCTGACCCTGCAGCAGCAG
CACCAGCGGCTGGCCCAGCTCCTCCTCATCCTCTCCCACATCAGGCACATGAGTAACAAA
GGCATGGAGCATCTGTACAGCATGAAGTGCAAGAACGTGGTGCCCCTCTATGACCTGCTG
CTGGAGATGCTGGACGCCCACCGCCTACATGCGCCCACTAGCCGTGGAGGGGCATCCGTG
GAGGAGACGGACCAAAGCCACTTGGCCACTGCGGGCTCTACTTCATCGCATTCCTTGCAA
AAGTATTACATCACGGGGGAGGCAGAGGGTTTCCCTGCCACAGTCTGA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
ESR1  |
| Target 1 GenAtlas ID |
ESR1  |
| Target 1 HGNC ID |
HGNC:3467  |
| Target 1 Chromosome Location |
6 |
| Target 1 Locus |
6q25.1 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS: An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6947-52. [PubMed
]
- Rogatsky I, Trowbridge JM, Garabedian MJ: Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex. J Biol Chem. 1999 Aug 6;274(32):22296-302. [PubMed
]
- Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW: A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J Biol Chem. 1999 Nov 26;274(48):34283-93. [PubMed
]
- Schubert EL, Lee MK, Newman B, King MC: Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility. J Steroid Biochem Mol Biol. 1999 Nov;71(1-2):21-7. [PubMed
]
- Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, Giguere V: CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol. 2001 Jan;21(1):343-53. [PubMed
]
- Shao W, Halachmi S, Brown M: ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May;22(10):3358-72. [PubMed
]
- Wong CW, McNally C, Nickbarg E, Komm BS, Cheskis BJ: Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14783-8. Epub 2002 Nov 1. [PubMed
]
- Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed
]
- Reese JC, Katzenellenbogen BS: Characterization of a temperature-sensitive mutation in the hormone binding domain of the human estrogen receptor. Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation. J Biol Chem. 1992 May 15;267(14):9868-73. [PubMed
]
- Schwabe JW, Neuhaus D, Rhodes D: Solution structure of the DNA-binding domain of the oestrogen receptor. Nature. 1990 Nov 29;348(6300):458-61. [PubMed
]
- 2792078 Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I, Chambon P: The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J. 1989 Jul;8(7):1981-6.
- 3753802 Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J: Sequence and expression of human estrogen receptor complementary DNA. Science. 1986 Mar 7;231(4742):1150-4.
- 3754034 Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P: Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13-19;320(6058):134-9.
- 7476978 Joel PB, Traish AM, Lannigan DA: Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Mol Endocrinol. 1995 Aug;9(8):1041-52.
- 7539106 Arnold SF, Obourn JD, Jaffe H, Notides AC: Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro. Mol Endocrinol. 1995 Jan;9(1):24-33.
- 7838153 Arnold SF, Obourn JD, Jaffe H, Notides AC: Serine 167 is the major estradiol-induced phosphorylation site on the human estrogen receptor. Mol Endocrinol. 1994 Sep;8(9):1208-14.
- 7916651 Pfeffer U, Fecarotta E, Castagnetta L, Vidali G: Estrogen receptor variant messenger RNA lacking exon 4 in estrogen-responsive human breast cancer cell lines. Cancer Res. 1993 Feb 15;53(4):741-3.
- 8221895 Schwabe JW, Chapman L, Finch JT, Rhodes D: The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements. Cell. 1993 Nov 5;75(3):567-78.
- 8600466 Pink JJ, Wu SQ, Wolf DM, Bilimoria MM, Jordan VC: A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7. Nucleic Acids Res. 1996 Mar 1;24(5):962-9.
- 8961262 McInerney EM, Ince BA, Shapiro DJ, Katzenellenbogen BS: A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action. Mol Endocrinol. 1996 Dec;10(12):1519-26.
- 9195227 Anderson TI, Wooster R, Laake K, Collins N, Warren W, Skrede M, Elles R, Tveit KM, Johnston SR, Dowsett M, Olsen AO, Moller P, Stratton MR, Borresen-Dale AL: Screening for ESR mutations in breast and ovarian cancer patients. Hum Mutat. 1997;9(6):531-6.
- 9338790 Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M: Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997 Oct 16;389(6652):753-8.
- 9600906 Tanenbaum DM, Wang Y, Williams SP, Sigler PB: Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. Proc Natl Acad Sci U S A. 1998 May 26;95(11):5998-6003.
- 9619507 Maalouf GJ, Xu W, Smith TF, Mohr SC: Homology model for the ligand-binding domain of the human estrogen receptor. J Biomol Struct Dyn. 1998 Apr;15(5):841-51.
- 9875847 Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL: The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998 Dec 23;95(7):927-37.
|
| Target 1 Drug References |
- Rabe T, Bohlmann MK, Rehberger-Schneider S, Prifti S: Induction of estrogen receptor-alpha and -beta activities by synthetic progestins. Gynecol Endocrinol. 2000 Apr;14(2):118-26. [PubMed
]
- Yamasaki K, Takeyoshi M, Yakabe Y, Sawaki M, Imatanaka N, Takatsuki M: Comparison of reporter gene assay and immature rat uterotrophic assay of twenty-three chemicals. Toxicology. 2002 Jan 15;170(1-2):21-30. [PubMed
]
- Yamasaki K, Takeyoshi M, Sawaki M, Imatanaka N, Shinoda K, Takatsuki M: Immature rat uterotrophic assay of 18 chemicals and Hershberger assay of 30 chemicals. Toxicology. 2003 Feb 1;183(1-3):93-115. [PubMed
]
- Jeng MH, Parker CJ, Jordan VC: Estrogenic potential of progestins in oral contraceptives to stimulate human breast cancer cell proliferation. Cancer Res. 1992 Dec 1;52(23):6539-46. [PubMed
]
- Jordan VC, Jeng MH, Catherino WH, Parker CJ: The estrogenic activity of synthetic progestins used in oral contraceptives. Cancer. 1993 Feb 15;71(4 Suppl):1501-5. [PubMed
]
|
|
Drug Target 2
[top]
|
| Target 2 ID |
556 |
| Target 2 Name |
Alpha-1A adrenergic receptor |
| Target 2 Synonyms |
- Alpha 1A- adrenoreceptor
- Alpha 1A-adrenoceptor
- Alpha adrenergic receptor 1c
- Alpha-1C adrenergic receptor
|
| Target 2 Gene Name |
ADRA1A |
| Target 2 Protein Sequence |
>Alpha-1A adrenergic receptor
MVFLSGNASDSSNCTQPPAPVNISKAILLGVILGGLILFGVLGNILVILSVACHRHLHSV
THYYIVNLAVADLLLTSTVLPFSAIFEVLGYWAFGRVFCNIWAAVDVLCCTASIMGLCII
SIDRYIGVSYPLRYPTIVTQRRGLMALLCVWALSLVISIGPLFGWRQPAPEDETICQINE
EPGYVLFSALGSFYLPLAIILVMYCRVYVVAKRESRGLKSGLKTDKSDSEQVTLRIHRKN
APAGGSGMASAKTKTHFSVRLLKFSREKKAAKTLGIVVGCFVLCWLPFFLVMPIGSFFPD
FKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLRIQCLCRKQSSKHALGYTL
HPPSQAVEGQHKDMVRIPVGSRETFYRISKTDGVCEWKFFSSMPRGSARITVSKDQSSCT
TARVRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV
|
| Target 2 Number of Residues |
473 |
| Target 2 Molecular Weight |
51487 |
| Target 2 Theoretical pI |
9.23 |
| Target 2 GO Classification |
|
Function
|
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha1-adrenergic receptor activity |
|
Process
|
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway |
|
Component
|
cell
membrane
intrinsic to membrane
integral to membrane |
|
| Target 2 General Function |
Involved in alpha1-adrenergic receptor activity |
| Target 2 Specific Function |
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins |
| Target 2 Pathways |
Not Available
|
| Target 2 Reactions |
Not Available |
| Target 2 Pfam Domain Function |
|
| Target 2 Signals |
|
| Target 2 Transmembrane Regions |
- 28-51
- 65-88
- 100-122
- 144-167
- 182-205
- 274-297
- 306-329
|
| Target 2 Essentiality |
Non-Essential |
| Target 2 GenBank ID Protein |
433201  |
| Target 2 UniProtKB/Swiss-Prot ID |
P35348  |
| Target 2 UniProtKB/Swiss-Prot Entry Name |
ADA1A_HUMAN  |
| Target 2 PDB ID |
Not Available |
| Target 2 Cellular Location |
- Membrane
- multi-pass membrane protein
|
| Target 2 Gene Sequence |
>1401 bp
ATGGTGTTTCTCTCGGGAAATGCTTCCGACAGCTCCAACTGCACCCAACCGCCGGCACCG
GTGAACATTTCCAAGGCCATTCTGCTCGGGGTGATCTTGGGGGGCCTCATTCTTTTCGGG
GTGCTGGGTAACATCCTAGTGATCCTCTCCGTAGCCTGTCACCGACACCTGCACTCAGTC
ACGCACTACTACATCGTCAACCTGGCGGTGGCCGACCTCCTGCTCACCTCCACGGTGCTG
CCCTTCTCCGCCATCTTCGAGGTCCTAGGCTACTGGGCCTTCGGCAGGGTCTTCTGCAAC
ATCTGGGCGGCAGTGGATGTGCTGTGCTGCACCGCGTCCATCATGGGCCTCTGCATCATC
TCCATCGACCGCTACATCGGCGTGAGCTACCCGCTGCGCTACCCAACCATCGTCACCCAG
AGGAGGGGTCTCATGGCTCTGCTCTGCGTCTGGGCACTCTCCCTGGTCATATCCATTGGA
CCCCTGTTCGGCTGGAGGCAGCCGGCCCCCGAGGACGAGACCATCTGCCAGATCAACGAG
GAGCCGGGCTACGTGCTCTTCTCAGCGCTGGGCTCCTTCTACCTGCCTCTGGCCATCATC
CTGGTCATGTACTGCCGCGTCTACGTGGTGGCCAAGAGGGAGAGCCGGGGCCTCAAGTCT
GGCCTCAAGACCGACAAGTCGGACTCGGAGCAAGTGACGCTCCGCATCCATCGGAAAAAC
GCCCCGGCAGGAGGCAGCGGGATGGCCAGCGCCAAGACCAAGACGCACTTCTCAGTGAGG
CTCCTCAAGTTCTCCCGGGAGAAGAAAGCGGCCAAAACGCTGGGCATCGTGGTCGGCTGC
TTCGTCCTCTGCTGGCTGCCTTTTTTCTTAGTCATGCCCATTGGGTCTTTCTTCCCTGAT
TTCAAGCCCTCTGAAACAGTTTTTAAAATAGTATTTTGGCTCGGATATCTAAACAGCTGC
ATCAACCCCATCATATACCCATGCTCCAGCCAAGAGTTCAAAAAGGCCTTTCAGAATGTC
TTGAGAATCCAGTGTCTCCGCAGAAAGCAGTCTTCCAAACATGCCCTGGGCTACACCCTG
CACCCGCCCAGCCAGGCCGTGGAAGGGCAACACAAGGACATGGTGCGCATCCCCGTGGGA
TCAAGAGAGACCTTCTACAGGATCTCCAAGACGGATGGCGTTTGTGAATGGAAATTTTTC
TCTTCCATGCCCCGTGGATCTGCCAGGATTACAGTGTCCAAAGACCAATCCTCCTGTACC
ACAGCCCGGGTGAGAAGTAAAAGCTTTTTGGAGGTCTGCTGCTGTGTAGGGCCCTCAACC
CCCAGCCTTGACAAGAACCATCAAGTTCCAACCATTAAGGTCCACACCATCTCCCTCAGT
GAGAACGGGGAGGAAGTCTAG
|
| Target 2 GenBank Gene ID |
|
| Target 2 GeneCard ID |
ADRA1A  |
| Target 2 GenAtlas ID |
ADRA1A  |
| Target 2 HGNC ID |
HGNC:277  |
| Target 2 Chromosome Location |
8 |
| Target 2 Locus |
8p21-p11.2 |
| Target 2 SNPs |
SNPJam Report  |
| Target 2 General References |
- Hirasawa A, Shibata K, Horie K, Takei Y, Obika K, Tanaka T, Muramoto N, Takagaki K, Yano J, Tsujimoto G: Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants. FEBS Lett. 1995 Apr 24;363(3):256-60. [PubMed
]
- Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ, et al.: Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther. 1995 Jan;272(1):134-42. [PubMed
]
- Weinberg DH, Trivedi P, Tan CP, Mitra S, Perkins-Barrow A, Borkowski D, Strader CD, Bayne M: Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c. Biochem Biophys Res Commun. 1994 Jun 30;201(3):1296-304. [PubMed
]
- Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA, et al.: The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8. [PubMed
]
- Hirasawa A, Horie K, Tanaka T, Takagaki K, Murai M, Yano J, Tsujimoto G: Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor. Biochem Biophys Res Commun. 1993 Sep 15;195(2):902-9. [PubMed
]
- Tseng-Crank J, Kost T, Goetz A, Hazum S, Roberson KM, Haizlip J, Godinot N, Robertson CN, Saussy D: The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br J Pharmacol. 1995 Aug;115(8):1475-85. [PubMed
]
- Chang DJ, Chang TK, Yamanishi SS, Salazar FH, Kosaka AH, Khare R, Bhakta S, Jasper JR, Shieh IS, Lesnick JD, Ford AP, Daniels DV, Eglen RM, Clarke DE, Bach C, Chan HW: Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms. FEBS Lett. 1998 Jan 30;422(2):279-83. [PubMed
]
|
| Target 2 Drug References |
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|
|
Drug Target 3
[top]
|
| Target 3 ID |
614 |
| Target 3 Name |
Progesterone receptor |
| Target 3 Synonyms |
- PR
|
| Target 3 Gene Name |
PGR |
| Target 3 Protein Sequence |
>Progesterone receptor
MTELKAKGPRAPHVAGGPPSPEVGSPLLCRPAAGPFPGSQTSDTLPEVSAIPISLDGLLF
PRPCQGQDPSDEKTQDQQSLSDVEGAYSRAEATRGAGGSSSSPPEKDSGLLDSVLDTLLA
PSGPGQSQPSPPACEVTSSWCLFGPELPEDPPAAPATQRVLSPLMSRSGCKVGDSSGTAA
AHKVLPRGLSPARQLLLPASESPHWSGAPVKPSPQAAAVEVEEEDGSESEESAGPLLKGK
PRALGGAAAGGGAAAVPPGAAAGGVALVPKEDSRFSAPRVALVEQDAPMAPGRSPLATTV
MDFIHVPILPLNHALLAARTRQLLEDESYDGGAGAASAFAPPRSSPCASSTPVAVGDFPD
CAYPPDAEPKDDAYPLYSDFQPPALKIKEEEEGAEASARSPRSYLVAGANPAAFPDFPLG
PPPPLPPRATPSRPGEAAVTAAPASASVSSASSSGSTLECILYKAEGAPPQQGPFAPPPC
KAPGASGCLLPRDGLPSTSASAAAAGAAPALYPALGLNGLPQLGYQAAVLKEGLPQVYPP
YLNYLRPDSEASQSPQYSFESLPQKICLICGDEASGCHYGVLTCGSCKVFFKRAMEGQHN
YLCAGRNDCIVDKIRRKNCPACRLRKCCQAGMVLGGRKFKKFNKVRVVRALDAVALPQPV
GVPNESQALSQRFTFSPGQDIQLIPPLINLLMSIEPDVIYAGHDNTKPDTSSSLLTSLNQ
LGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAP
DLILNEQRMKESSFYSLCLTMWQIPQEFVKLQVSQEEFLCMKVLLLLNTIPLEGLRSQTQ
FEEMRSSYIRELIKAIGLRQKGVVSSSQRFYQLTKLLDNLHDLVKQLHLYCLNTFIQSRA
LSVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK
|
| Target 3 Number of Residues |
948 |
| Target 3 Molecular Weight |
98982 |
| Target 3 Theoretical pI |
6.45 |
| Target 3 GO Classification |
|
Function
|
steroid binding
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity |
|
Process
|
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent |
|
Component
|
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus |
|
| Target 3 General Function |
Involved in transcription factor activity |
| Target 3 Specific Function |
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues |
| Target 3 Pathways |
Not Available
|
| Target 3 Reactions |
Not Available |
| Target 3 Pfam Domain Function |
|
| Target 3 Signals |
|
| Target 3 Transmembrane Regions |
|
| Target 3 Essentiality |
Non-Essential |
| Target 3 GenBank ID Protein |
35652  |
| Target 3 UniProtKB/Swiss-Prot ID |
P06401  |
| Target 3 UniProtKB/Swiss-Prot Entry Name |
PRGR_HUMAN  |
| Target 3 PDB ID |
1SQN  |
| Target 3 PDB File |
Show |
| Target 3 3D Structure |
|
| Target 3 Cellular Location |
|
| Target 3 Gene Sequence |
>2802 bp
ATGACTGAGCTGAAGGCAAAGGGTCCCCGGGCTCCCCACGTGGCGGGCGGCCCGCCCTCC
CCCGAGGTCGGATCCCCACTGCTGTGTCGCCCAGCCGCAGGTCCGTTCCCGGGGAGCCAG
ACCTCGGACACCTTGCCTGAAGTTTCGGCCATACCTATCTCCCTGGACGGGCTACTCTTC
CCTCGGCCCTGCCAGGGACAGGACCCCTCCGACGAAAAGACGCAGGACCAGCAGTCGCTG
TCGGACGTGGAGGGCGCATATTCCAGAGCTGAAGCTACAAGGGGTGCTGGAGGCAGCAGT
TCTAGTCCCCCAGAAAAGGACAGCGGACTGCTGGACAGTGTCTTGGACACTCTGTTGGCG
CCCTCAGGTCCCGGGCAGAGCCAACCCAGCCCTCCCGCCTGCGAGGTCACCAGCTCTTGG
TGCCTGTTTGGCCCCGAACTTCCCGAAGATCCACCGGCTGCCCCCGCCACCCAGCGGGTG
TTGTCCCCGCTCATGAGCCGGTCCGGGTGCAAGGTTGGAGACAGCTCCGGGACGGCAGCT
GCCCATAAAGTGCTGCCCCGGGGCCTGTCACCAGCCCGGCAGCTGCTGCTCCCGGCCTCT
GAGAGCCCTCACTGGTCCGGGGCCCCAGTGAAGCCGTCTCCGCAGGCCGCTGCGGTGGAG
GTTGAGGAGGAGGATAGCTCTGAGTCCGAGGAGTCTGCGGGTCCGCTTCTGAAGGGCAAA
CCTCGGGCTCTGGGTGGCGCGGCGGCTGGAGGAGGAGCCGCGGCTTGTCCGCCGGGGGCG
GCAGCAGGAGGCGTCGCCCTGGTCCCCAAGGAAGATTCCCGCTTCTCAGCGCCCAGGGTC
GCCCTGGTGGAGCAGGACGCGCCGATGGCGCCCGGGCGCTCCCCGCTGGCCACCACGGTG
ATGGATTTCATCCACGTGCCTATCCTGCCTCTCAATCACGCCTTATTGGCAGCCCGCACT
CGGCAGCTGCTGGAAGACGAAAGTTACGACGGCGGGGCCGGGGCTGCCAGCGCCTTTGCC
CCGCCGCGGACTTCACCCTGTGCCTCGTCCACCCCGGTCGCTGTAGGCGACTTCCCCGAC
TGCGCGTACCCGCCCGACGCCGAGCCCAAGGACGACGCGTACCCTCTCTATAGCGACTTC
CAGCCGCCCGCTCTAAAGATAAAGGAGGAGGAGGAAGGCGCGGAGGCCTCCGCGCGCTCC
CCGCGTTCCTACCTTGTGGCCGGTGCCAACCCCGCAGCCTTCCCGGATTTCCCGTTGGGG
CCACCGCCCCCGCTGCCGCCGCGAGCGACCCCATCCAGACCCGGGGAAGCGGCGGTGACG
GCCGCACCCGCCAGTGCCTCAGTCTCGTCTGCGTCCTCCTCGGGGTCGACCCTGGAGTGC
ATCCTGTACAAAGCGGAGGGCGCGCCGCCCCAGCAGGGCCCGTTCGCGCCGCCGCCCTGC
AAGGCGCCGGGCGCGAGCGGCTGCCTGCTCCCGCGGGACGGCCTGCCCTCCACCTCCGCC
TCTGCCGCCGCCGCCGGGGCGGCCCCCGCGCTCTACCCTGCACTCGGCCTCAACGGGCTC
CCGCAGCTCGGCTACCAGGCCGCCGTGCTCAAGGAGGGCCTGCCGCAGGTCTACCCGCCC
TATCTCAACTACCTGAGGCCGGATTCAGAAGCCAGCCAGAGCCCACAATACAGCTTCGAG
TCATTACCTCAGAAGATTTGTTTAATCTGTGGGGATGAAGCATCAGGCTGTCATTATGGT
GTCCTTACCTGTGGGAGCTGTAAGGTCTTCTTTAAGAGGGCAATGGAAGGGCAGCACAAC
TACTTATGTGCTGGAAGAAATGACTGCATCGTTGATAAAATCCGCAGAAAAAACTGCCCA
GCATGTCGCCTTAGAAAGTGCTGTCAGGCTGGCATGGTCCTTGGAGGTCGAAAATTTAAA
AAGTTCAATAAAGTCAGAGTTGTGAGAGCACTGGATGCTGTTGCTCTCCCACAGCCATTG
GGCGTTCCAAATGAAAGCCAAGCCCTAAGCCAGAGATTCACTTTTTCACCAGGTCAAGAC
ATACAGTTGATTCCACCACTGATCAACCTGTTAATGAGCATTGAACCAGATGTGATCTAT
GCAGGACATGACAACACAAAACCTGACACCTCCAGTTCTTTGCTGACAAGTCTTAATCAA
CTAGGCGAGAGGCAACTTCTTTCAGTAGTCAAGTGGTCTAAATCATTGCCAGGTTTTCGA
AACTTACATATTGATGACCAGATAACTCTCATTCAGTATTCTTGGATGAGCTTAATGGTG
TTTGGTCTAGGATGGAGATCCTACAAACATGTCAGTGGGCAGATGCTGTATTTTGCACCT
GATCTAATACTAAATGAACAGCGGATGAAAGAATCATCATTCTATTCATTATGCCTTACC
ATGTGGCAGATCCCACAGGAGTTTGTCAAGCTTCAAGTTAGCCAAGAAGAGTTCCTCTGT
ATGAAAGTATTGTTACTTCTTAATACAATTCCTTTGGAAGGGCTACGAAGTCAAACCCAG
TTTGAGGAGATGAGGTCAAGCTACATTAGAGAGCTCATCAAGGCAATTGGTTTGAGGCAA
AAAGGAGTTGTGTCGAGCTCACAGCGTTTCTATCAACTTACAAAACTTCTTGATAACTTG
CATGATCTTGTCAAACAGCTTCATCTGTACTGCTTGAATACATTTATCCAGTCCCGGGCA
CTGAGTGTTGAATTTCCAGAAATGATGTCTGAAGTTATTGCTGCACAATTACCCAAGATA
TTGGCAGGGATGGTGAAACCCCTTCTCTTTCATAAAAAGTGA
|
| Target 3 GenBank Gene ID |
|
| Target 3 GeneCard ID |
PGR  |
| Target 3 GenAtlas ID |
PGR  |
| Target 3 HGNC ID |
HGNC:8910  |
| Target 3 Chromosome Location |
11 |
| Target 3 Locus |
11q22-q23 |
| Target 3 SNPs |
SNPJam Report  |
| Target 3 General References |
- Knotts TA, Orkiszewski RS, Cook RG, Edwards DP, Weigel NL: Identification of a phosphorylation site in the hinge region of the human progesterone receptor and additional amino-terminal phosphorylation sites. J Biol Chem. 2001 Mar 16;276(11):8475-83. Epub 2000 Dec 7. [PubMed
]
- Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P: Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 1990 May;9(5):1603-14. [PubMed
]
- Misrahi M, Atger M, d'Auriol L, Loosfelt H, Meriel C, Fridlansky F, Guiochon-Mantel A, Galibert F, Milgrom E: Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem Biophys Res Commun. 1987 Mar 13;143(2):740-8. [PubMed
]
- Williams SP, Sigler PB: Atomic structure of progesterone complexed with its receptor. Nature. 1998 May 28;393(6683):392-6. [PubMed
]
|
| Target 3 Drug References |
- Jeng MH, Parker CJ, Jordan VC: Estrogenic potential of progestins in oral contraceptives to stimulate human breast cancer cell proliferation. Cancer Res. 1992 Dec 1;52(23):6539-46. [PubMed
]
- Okada H: [Progestogen therapy in the treatment of endometrial cancer--clinical results and mechanism of steroid action] Gan To Kagaku Ryoho. 1988 Apr;15(4 Pt 2-1):924-8. [PubMed
]
- Nielsen ST, Conaty JM, DiPasquale G: Progesterone receptor of adult rabbit lung. Pharmacology. 1987;35(4):217-26. [PubMed
]
- White JO, Moore PA, Marr W, Elder MG, Lim L: Comparative effects of progesterone, norgestrel, norethisterone and tamoxifen on the abnormal uterus of the anovulatory rat. Biochem J. 1982 Oct 15;208(1):199-204. [PubMed
]
- Corson SL: Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate. Am J Obstet Gynecol. 1994 May;170(5 Pt 2):1556-61. [PubMed
]
|