Allylestrenol

Targets (2)Enzymes (1)Biointeractions (3)

Identification

Name
Allylestrenol
Accession Number
DB01431
Type
Small Molecule
Groups
Experimental
Description

A synthetic steroid with progestational activity. It is widely marketed throughout Europe, including Russia and many other European countries, and is also available in Japan, Hong Kong, India, Bangladesh, Indonesia, and much of Southeast Asia, though notably not in the United States or Canada.

Structure
Thumb
3D
Similar Structures
Synonyms
  • 17α-allylestr-4-en-17β-ol
  • 3-deketo-17α-allyl-19-nortestosterone
  • Allyl estrenol
  • Allyloestrenol
External IDs
NSC-37723
International/Other Brands
Gestanin / Gestanol / Gestanon / Gestin / Gestrenol / Maintaine / Orageston / Perselin / Profar / Turinal
Categories
UNII
I47VB5DZ8O
CAS number
432-60-0
Weight
Average: 300.4782
Monoisotopic: 300.245315646
Chemical Formula
C21H32O
InChI Key
ATXHVCQZZJYMCF-XUDSTZEESA-N
InChI
InChI=1S/C21H32O/c1-3-12-21(22)14-11-19-18-9-8-15-6-4-5-7-16(15)17(18)10-13-20(19,21)2/h3,6,16-19,22H,1,4-5,7-14H2,2H3/t16-,17+,18+,19-,20-,21-/m0/s1
IUPAC Name
(1S,2R,10R,11S,14R,15S)-15-methyl-14-(prop-2-en-1-yl)tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-ol
SMILES
[H][C@@]12CC[C@@](O)(CC=C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCCC=C3CC[C@@]21[H]

Pharmacology

Indication

Allylestrenol was designed to be used for miscarriage prevention, prevention of premature labour and has been investigated for possible use in men for treatment for benign prostatic hyperplasia.

Pharmacodynamics

Allylestrenol is a progestogen structurally related to progesterone that has been given in threatened and recurrent miscarriage, and to prevent premature labour. However, with the exception of proven progesterone deficiency, such use is no longer recommended. In threatened miscarriage in progesterone-deficient women a suggested dose is 5 mg three times daily by mouth for 5 to 7 days.

Mechanism of action

Allylestrenol is similar in structure and function to progesterone. Progesterone shares the pharmacological actions of the progestins. Progesterone 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 Progesterone will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. In women who have adequate endogenous estrogen, progesterone transforms a proliferative endometrium into a secretory one. Progesterone is essential for the development of decidual tissue and is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo has been implanted, progesterone acts to maintain the pregnancy. Progesterone also stimulates the growth of mammary alveolar tissue and relaxes uterine smooth muscle. It has little estrogenic and androgenic activity.

TargetActionsOrganism
AProgesterone receptor
agonist
Humans
UEstrogen receptor alpha
agonist
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

The glucuronide and sulfate conjugates of pregnanediol and pregnanolone are excreted in the urine and bile. Progesterone metabolites which are excreted in the bile may undergo enterohepatic recycling or may be excreted in the feces. Progesterone metabolites are excreted mainly by the kidneys.

Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinAllylestrenol may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinAllylestrenol may decrease the anticoagulant activities of (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Allylestrenol.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Allylestrenol.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Allylestrenol.
6-Deoxyerythronolide BThe metabolism of Allylestrenol can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Allylestrenol.
7-ethyl-10-hydroxycamptothecinThe metabolism of Allylestrenol can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Allylestrenol.
AbacavirAbacavir may decrease the excretion rate of Allylestrenol which could result in a higher serum level.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015500
KEGG Drug
D01374
KEGG Compound
C12811
PubChem Compound
235905
PubChem Substance
46506946
ChemSpider
205855
ChEBI
31189
ChEMBL
CHEMBL3185133
Therapeutic Targets Database
DPR000085
PharmGKB
PA164745307
Wikipedia
Allylestrenol
ATC Codes
G03DC01 — Allylestrenol

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)80 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.000558 mg/mLALOGPS
logP5.14ALOGPS
logP4.83ChemAxon
logS-5.7ALOGPS
pKa (Strongest Basic)-0.17ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity93.14 m3·mol-1ChemAxon
Polarizability37.17 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9966
Blood Brain Barrier+0.9817
Caco-2 permeable+0.8469
P-glycoprotein substrateSubstrate0.6615
P-glycoprotein inhibitor IInhibitor0.5781
P-glycoprotein inhibitor IINon-inhibitor0.795
Renal organic cation transporterNon-inhibitor0.6625
CYP450 2C9 substrateNon-substrate0.807
CYP450 2D6 substrateNon-substrate0.9046
CYP450 3A4 substrateSubstrate0.6941
CYP450 1A2 substrateNon-inhibitor0.8345
CYP450 2C9 inhibitorNon-inhibitor0.8006
CYP450 2D6 inhibitorNon-inhibitor0.9427
CYP450 2C19 inhibitorInhibitor0.5498
CYP450 3A4 inhibitorNon-inhibitor0.8408
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6449
Ames testNon AMES toxic0.936
CarcinogenicityNon-carcinogens0.9458
BiodegradationNot ready biodegradable0.9828
Rat acute toxicity2.4200 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6669
hERG inhibition (predictor II)Non-inhibitor0.7541
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrane steroids
Alternative Parents
17-hydroxysteroids / Delta-4-steroids / Tertiary alcohols / Cyclic alcohols and derivatives / Hydrocarbon derivatives
Substituents
17-hydroxysteroid / Hydroxysteroid / Estrane-skeleton / Delta-4-steroid / Tertiary alcohol / Cyclic alcohol / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Alcohol
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
steroid (CHEBI:31189) / Estrane and derivatives, C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C12811) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030125)

Targets

Details1. Progesterone receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
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. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Madauss KP, Stewart EL, Williams SP: The evolution of progesterone receptor ligands. Med Res Rev. 2007 May;27(3):374-400. [PubMed:17013809]
  2. Gizard F, Robillard R, Gross B, Barbier O, Revillion F, Peyrat JP, Torpier G, Hum DW, Staels B: TReP-132 is a novel progesterone receptor coactivator required for the inhibition of breast cancer cell growth and enhancement of differentiation by progesterone. Mol Cell Biol. 2006 Oct;26(20):7632-44. [PubMed:17015480]
  3. Wu HB, Fabian S, Jenab S, Quinones-Jenab V: Progesterone receptors activation after acute cocaine administration. Brain Res. 2006 Dec 18;1126(1):188-92. Epub 2006 Nov 15. [PubMed:17109827]
  4. Boonyaratanakornkit V, McGowan E, Sherman L, Mancini MA, Cheskis BJ, Edwards DP: The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Mol Endocrinol. 2007 Feb;21(2):359-75. Epub 2006 Nov 30. [PubMed:17138644]
  5. Tranguch S, Smith DF, Dey SK: Progesterone receptor requires a co-chaperone for signalling in uterine biology and implantation. Reprod Biomed Online. 2006 Nov;13(5):651-60. [PubMed:17169175]
  6. Bergink EW, Loonen PB, Kloosterboer HJ: Receptor binding of allylestrenol, a progestagen of the 19-nortestosterone series without androgenic properties. J Steroid Biochem. 1985 Aug;23(2):165-8. [PubMed:3928974]
Details2. Estrogen receptor alpha
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
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 tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Kumar AS, Cureton E, Shim V, Sakata T, Moore DH, Benz CC, Esserman LJ, Hwang ES: Type and duration of exogenous hormone use affects breast cancer histology. Ann Surg Oncol. 2007 Feb;14(2):695-703. Epub 2006 Nov 14. [PubMed:17103262]
  2. Lessey BA, Palomino WA, Apparao KB, Young SL, Lininger RA: Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006;4 Suppl 1:S9. [PubMed:17118173]
  3. Yuri T, Tsukamoto R, Uehara N, Matsuoka Y, Tsubura A: Effects of different durations of estrogen and progesterone treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats. In Vivo. 2006 Nov-Dec;20(6B):829-36. [PubMed:17203775]
  4. Montero Girard G, Vanzulli SI, Cerliani JP, Bottino MC, Bolado J, Vela J, Becu-Villalobos D, Benavides F, Gutkind S, Patel V, Molinolo A, Lanari C: Association of estrogen receptor-alpha and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment. Breast Cancer Res. 2007;9(2):R22. [PubMed:17341305]
  5. Ghebeh H, Tulbah A, Mohammed S, Elkum N, Bin Amer SM, Al-Tweigeri T, Dermime S: Expression of B7-H1 in breast cancer patients is strongly associated with high proliferative Ki-67-expressing tumor cells. Int J Cancer. 2007 Aug 15;121(4):751-8. [PubMed:17415709]
  6. Csaba G, Gonda AI, Karabelyos C: Contraceptive treatment increases the affinity of uterine estrogen receptor in adult rat: perinatal gestagen treatment changes the reaction. Horm Metab Res. 1996 Jan;28(1):16-9. [PubMed:8820988]

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on July 24, 2007 10:58 / Updated on November 02, 2018 05:01