T3DB: 17-Hydroxyprogesterone caproate

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (7)XML

Targets (7)

Record Information

Version

2.0

Creation Date

2014-09-11 05:16:53 UTC

Update Date

2014-12-24 20:26:57 UTC

Accession Number

T3D4792

Identification

Common Name

17-Hydroxyprogesterone caproate

Class

Small Molecule

Description

17α-Hydroxyprogesterone caproate is a synthetic steroid hormone that is similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone formed from caproic acid (hexanoic acid). 17α-Hydroxyprogesterone caproate was previously marketed under the trade name Delalutin by Squibb, which was approved by the U.S. Food and Drug Administration (FDA) in 1956 and withdrawn from marketing in 1999. Cytyc is seeking FDA approval to market 17α-hydroxyprogesterone caproate under the trade name Gestiva for prevention of preterm delivery in women with a history of preterm delivery. [Wikipedia]

Compound Type

Drug
Food Toxin
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
17a-Hydroxyprogesterone caproate
17alpha-Hydroxyprogesterone caproate
17α-Hydroxyprogesterone caproate

Chemical Formula

C₂₇H₄₀O₄

Average Molecular Mass

428.604 g/mol

Monoisotopic Mass

428.293 g/mol

CAS Registry Number

630-56-8

IUPAC Name

(1S,2R,10R,11S,14R,15S)-14-acetyl-2,15-dimethyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-yl hexanoate

Traditional Name

proge

SMILES

[H][C@@]12CC[C@](OC(=O)CCCCC)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C

InChI Identifier

InChI=1S/C27H40O4/c1-5-6-7-8-24(30)31-27(18(2)28)16-13-23-21-10-9-19-17-20(29)11-14-25(19,3)22(21)12-15-26(23,27)4/h17,21-23H,5-16H2,1-4H3/t21-,22+,23+,25+,26+,27+/m1/s1

InChI Key

InChIKey=DOMWKUIIPQCAJU-LJHIYBGHSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Steroids and steroid derivatives

Sub Class

Pregnane steroids

Direct Parent

Gluco/mineralocorticoids, progestogins and derivatives

Alternative Parents

Substituents

Progestogin-skeleton
Steroid ester
20-oxosteroid
3-oxo-delta-4-steroid
3-oxosteroid
Oxosteroid
Delta-4-steroid
Cyclohexenone
Alpha-acyloxy ketone
Carboxylic acid ester
Cyclic ketone
Ketone
Carboxylic acid derivative
Monocarboxylic acid or derivatives
Organic oxide
Hydrocarbon derivative
Organic oxygen compound
Carbonyl group
Organooxygen compound
Aliphatic homopolycyclic compound

Molecular Framework

Aliphatic homopolycyclic compounds

External Descriptors

corticosteroid hormone (CHEBI:5812 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Not Available

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	119-121°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00087 g/L	ALOGPS
logP	4.81	ALOGPS
logP	5.88	ChemAxon
logS	-5.7	ALOGPS
pKa (Strongest Acidic)	17.81	ChemAxon
pKa (Strongest Basic)	-4.8	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	60.44 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	121.69 m³·mol⁻¹	ChemAxon
Polarizability	50.09 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-004i-2950000000-2239a8a809fdd9396eaf	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0aba-3940000000-835c32531e48d578d8ee	2017-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-01ta-5016900000-d55ac0fcfd38f6b1e0c8	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-06sj-9066100000-0190e2cb3e354ad5855b	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-2190000000-6cb10f57437638e6f339	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-1204900000-5176dc1a9b613d11298a	2016-08-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004r-3139200000-a319c246dda8baaad8db	2016-08-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-01rl-9178000000-78a905d5e4c60c4ab5f6	2016-08-04	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

2B, possibly carcinogenic to humans. (1)

Uses/Sources

Not Available

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

169870

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

17-Hydroxyprogesterone_caproate

References

Synthesis Reference

Not Available

MSDS

T3D4792.pdf

General References

International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Estrogen receptor

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 tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:: ESR1
Uniprot ID:: P03372
Molecular Weight:: 66215.45 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.0061 uM	ACEA_T47D_80hr_Positive	ACEA Biosciences

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

2. Androgen receptor

General Function:: Zinc ion binding
Specific Function:: Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:: AR
Uniprot ID:: P10275
Molecular Weight:: 98987.9 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.282 uM	NVS_NR_hAR	Novascreen
AC50	3.19 uM	Tox21_AR_BLA_Antagonist_ratio	Tox21/NCGC
AC50	0.0666 uM	Tox21_AR_LUC_MDAKB2_Agonist	Tox21/NCGC

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

3. Glucocorticoid receptor

General Function:: Zinc ion binding
Specific Function:: Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
Gene Name:: NR3C1
Uniprot ID:: P04150
Molecular Weight:: 85658.57 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.383 uM	ATG_GR_TRANS	Attagene
AC50	0.114 uM	Tox21_GR_BLA_Antagonist_ratio	Tox21/NCGC

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

4. Nuclear receptor subfamily 1 group I member 2

General Function:: Zinc ion binding
Specific Function:: Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:: NR1I2
Uniprot ID:: O75469
Molecular Weight:: 49761.245 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.42 uM	ATG_PXR_TRANS	Attagene
AC50	0.354 uM	ATG_PXRE_CIS	Attagene

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

5. Progesterone receptor

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 isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:: PGR
Uniprot ID:: P06401
Molecular Weight:: 98979.96 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	1.85 uM	NVS_NR_hPR	Novascreen

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

6. Bile acid receptor

General Function:: Zinc ion binding
Specific Function:: Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:: NR1H4
Uniprot ID:: Q96RI1
Molecular Weight:: 55913.915 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	5.32 uM	OT_SRC1_SRC1FXR_0480	Odyssey Thera
AC50	3.73 uM	OT_SRC1_SRC1FXR_1440	Odyssey Thera

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

7. Estrogen receptor beta

General Function:: Zinc ion binding
Specific Function:: Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:: ESR2
Uniprot ID:: Q92731
Molecular Weight:: 59215.765 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	3.96 uM	OT_ER_ERaERb_1440	Odyssey Thera
AC50	4.5 uM	OT_ER_ERbERb_1440	Odyssey Thera

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

17-Hydroxyprogesterone caproate (T3D4792)

Structure for T3D4792: 17-Hydroxyprogesterone caproate

Targets

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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