Testosterone propionate

First marketed in 1937

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H32O3
Molecular Weight	344.4877
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@H](OC(=O)CC)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CCC4=CC(=O)CC[C@]34C

InChI

InChIKey=PDMMFKSKQVNJMI-BLQWBTBKSA-N

InChI=1S/C22H32O3/c1-4-20(24)25-19-8-7-17-16-6-5-14-13-15(23)9-11-21(14,2)18(16)10-12-22(17,19)3/h13,16-19H,4-12H2,1-3H3/t16-,17-,18-,19-,21-,22-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00624
Curator's Comment: Description was created based on several sources, including

Testosterone is a steroid sex hormone found in both men and women. In men, testosterone is produced primarily by the Leydig (interstitial) cells of the testes when stimulated by luteinizing hormone (LH). It functions to stimulate spermatogenesis, promote physical and functional maturation of spermatozoa, maintain accessory organs of the male reproductive tract, support development of secondary sexual characteristics, stimulate growth and metabolism throughout the body and influence brain development by stimulating sexual behaviors and sexual drive. In women, testosterone is produced by the ovaries (25%), adrenals (25%) and via peripheral conversion from androstenedione (50%). Testerone in women functions to maintain libido and general wellbeing. Testosterone exerts a negative feedback mechanism on pituitary release of LH and follicle-stimulating hormone (FSH). Testosterone may be further converted to dihydrotestosterone or estradiol depending on the tissue. The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 2.5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects. Testosterone is used as hormone replacement or substitution of diminished or absent endogenous testosterone. Use in males: For management of congenital or acquired hypogonadism, hypogonadism associated with HIV infection, and male climacteric (andopause). Use in females: For palliative treatment of androgen-responsive, advanced, inoperable, metastatis (skeletal) carcinoma of the breast in women who are 1-5 years postmenopausal; testosterone esters may be used in combination with estrogens in the management of moderate to severe vasomotor symptoms associated with menopause in women who do not respond to adequately to estrogen therapy alone.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen receptor 42 Target ID: P10275 Gene ID: 367.0 Gene Symbol: AR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17635942	Agonist 2678
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19856921	Agonist 2678		3.16 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypogonadism 28 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203098s006lbl.pdf	Primary		Approved 8429	TESTOSTERONE Approved Use Testosterone is an androgen indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: • Primary Hypogonadism (Congenital or Acquired) (1) • Hypogonadotropic Hypogonadism (Congenital or Acquired) Launch Date 2013

C_max

Value	Dose	Analyte	Population
13.1 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10902784/	8.2 mg single, topical dose: 8.2 mg route of administration: Topical experiment type: SINGLE co-administered:	TESTOSTERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
214 ng/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01725451	30 mg single, topical dose: 30 mg route of administration: topical experiment type: single co-administered:	TESTOSTERONE unknown	Homo sapiens population: healthy age: sex: food status:
231 ng/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01725451	30 mg single, topical dose: 30 mg route of administration: topical experiment type: single co-administered:	TESTOSTERONE unknown	Homo sapiens population: healthy age: sex: food status:
930.1 ng/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01386606	5 g 1 times / day multiple, topical dose: 5 g route of administration: topical experiment type: multiple co-administered:	TESTOSTERONE unknown	Homo sapiens

AUC

Value	Dose	Analyte	Population
948 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10902784/	8.2 mg single, topical dose: 8.2 mg route of administration: Topical experiment type: SINGLE co-administered:	TESTOSTERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
2120 ng*h/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01725451	30 mg single, topical dose: 30 mg route of administration: topical experiment type: single co-administered:	TESTOSTERONE unknown	Homo sapiens population: healthy age: sex: food status:
3110 ng*h/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01725451	30 mg single, topical dose: 30 mg route of administration: topical experiment type: single co-administered:	TESTOSTERONE unknown	Homo sapiens population: healthy age: sex: food status:

T_1/2

Value	Dose	Co-administered	Analyte	Population
7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10902784/	8.2 mg single, topical dose: 8.2 mg route of administration: Topical experiment type: SINGLE co-administered:		TESTOSTERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
13% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10902784/	8.2 mg single, topical dose: 8.2 mg route of administration: Topical experiment type: SINGLE co-administered:		TESTOSTERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
75 mg 1 times / day steady, subcutaneous (median) Recommended Dose: 75 mg, 1 times / day Route: subcutaneous Route: steady Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30296416/	unhealthy, adult n = 150 Health Status: unhealthy Condition: hypogonadism Age Group: adult Sex: M Population Size: 150 Sources: https://pubmed.ncbi.nlm.nih.gov/30296416/	Disc. AE: Hypertension... AEs leading to discontinuation/dose reduction: Hypertension (5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/30296416/
100 mg 1 times / day steady, topical Recommended Dose: 100 mg, 1 times / day Route: topical Route: steady Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20592293/	unhealthy, mean 74 years n = 106 Health Status: unhealthy Condition: with limitations in mobility Age Group: mean 74 years Sex: M Population Size: 106 Sources: https://pubmed.ncbi.nlm.nih.gov/20592293/	Other AEs: Cardiac disorders, Atherosclerosis... Other AEs: Cardiac disorders (6.5%) Atherosclerosis (6.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/20592293/

AEs

AE	Significance	Dose	Population
Hypertension	5.6% Disc. AE	75 mg 1 times / day steady, subcutaneous (median) Recommended Dose: 75 mg, 1 times / day Route: subcutaneous Route: steady Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30296416/	unhealthy, adult n = 150 Health Status: unhealthy Condition: hypogonadism Age Group: adult Sex: M Population Size: 150 Sources: https://pubmed.ncbi.nlm.nih.gov/30296416/
Atherosclerosis	6.4%	100 mg 1 times / day steady, topical Recommended Dose: 100 mg, 1 times / day Route: topical Route: steady Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20592293/	unhealthy, mean 74 years n = 106 Health Status: unhealthy Condition: with limitations in mobility Age Group: mean 74 years Sex: M Population Size: 106 Sources: https://pubmed.ncbi.nlm.nih.gov/20592293/
Cardiac disorders	6.5%	100 mg 1 times / day steady, topical Recommended Dose: 100 mg, 1 times / day Route: topical Route: steady Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20592293/	unhealthy, mean 74 years n = 106 Health Status: unhealthy Condition: with limitations in mobility Age Group: mean 74 years Sex: M Population Size: 106 Sources: https://pubmed.ncbi.nlm.nih.gov/20592293/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 P-gp 1461 MRP2 383	UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A5 55 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 291 UGT2A1 32 UGT2A2 48 UGT2A3 48 UGT2B4 249 UGT2B7 389 UGT2B10 127 UGT2B15 203 UGT2B17 213 UGT2B28 63 CYP3A5 395 CYP3A7 110 P-gp 1537	MCT4 19 P-gp 257

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0 Page: -	no
MRP2 475	inhibitor 3277 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0 Page: -	no
P-gp 1650	inhibitor 3277 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0 Page: -	no
MCT4 28	inducer 1573 Sources: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/jphysiol.2006.115436 Page: -	yes
P-gp 1650	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S0024320506000786 Page: -	yes

Drug as victim

Target	Modality	Activity
UGT2B17 213	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	major [Km 10 uM]
UGT2A1 32	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	major [Km 38.7 uM]
UGT1A10 291	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A3 422	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A4 347	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A8 283	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A9 380	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT2A2 48	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT2B15 203	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT2B7 389	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A1 418	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT1A5 55	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT1A6 307	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT1A7 236	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT2A3 48	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT2B10 127	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT2B28 63	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT2B4 249	substrate 3367 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
CYP3A4 1737	substrate 3367 Sources: https://jpet.aspetjournals.org/content/299/3/825.short Page: -	yes
CYP3A5 395	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697443/ Page: -	yes
CYP3A7 110	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697443/ Page: -	yes
P-gp 1537	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006291X19317887 Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:17347	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:17347
ChemicalBook	CB5380541	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5380541
ZINC	ZINC000118912393	http://zinc15.docking.org/substances/ZINC000118912393
eMolecules	511977	https://www.emolecules.com/cgi-bin/more?vid=511977

PubMed

Title	Date	PubMed
Leydig cells.	1975 May	1095296
Study on steroidal oximinoethers: synthesis and stereostructure by NMR spectroscopy.	1999 Apr	10399880
Testosterone induces vascular endothelial growth factor synthesis in the ventral prostate in castrated rats.	1999 May	10210429
Elevation of steroid 5 alpha-reductase mRNA levels in rat cerebellum by toluene inhalation: possible relation to GFAP expression.	2000 Aug	10987130
Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity.	2000 Aug	10975606
Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene.	2000 Nov	11075820
Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study.	2000 Oct 17	11034937
Psychophysiological responses to the Stroop Task after a maximal cycle ergometry in elite sportsmen and physically active subjects.	2001 Feb	11166107
Spz1, a novel bHLH-Zip protein, is specifically expressed in testis.	2001 Feb	11165476
Effects of the anti-androgen finasteride on the modulatory actions of oestradiol on androgen metabolism by human gingival fibroblasts.	2001 Feb	11163318
Castration in Gambel's and Scaled Quail: ornate plumage and dominance persist, but courtship and threat behaviors do not.	2001 Feb	11161878
cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450.	2001 Feb	11160876
Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes.	2001 Feb	11159803
Photoperiod-induced testicular apoptosis in European starlings (Sturnus vulgaris).	2001 Feb	11159376
Neuroendocrine regulation of sexually dimorphic brain structure and associated sexual behavior in male rats is genetically controlled.	2001 Feb	11159360
Evidence that cyproterone acetate improves psychological symptoms and enhances the activity of the dopaminergic system in postmenopause.	2001 Feb	11158017
Androgen deficiency in women with hypopituitarism.	2001 Feb	11158009
Muting of androgen negative feedback unveils impoverished gonadotropin-releasing hormone/luteinizing hormone secretory reactivity in healthy older men.	2001 Feb	11158004
Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance.	2001 Feb	11158002
Disparate response of wild-type and variant forms of LH to GnRH stimulation in individuals heterozygous for the LHbeta variant allele.	2001 Feb	11157812
Estrogen and androgen elicit growth hormone release via dissimilar patterns of hypothalamic neuropeptide secretion.	2001 Feb	11146085
Testosterone concentrations in women aged 25-50 years: associations with lifestyle, body composition, and ovarian status.	2001 Feb 1	11157413
Neuronal size in the spinal nucleus of the bulbocavernosus: direct modulation by androgen in rats with mosaic androgen insensitivity.	2001 Feb 1	11157092
Porcine gonadal and placental isozymes of aromatase cytochrome P450: sub-cellular distribution and support by NADPH-cytochrome P450 reductase.	2001 Feb 14	11165045
Changes in androgenic steroid profile due to urine contamination by microorganisms: a prospective study in the context of doping control.	2001 Feb 15	11161304
Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer.	2001 Jan	11164157
Concentrations of steroid hormones in layers and biopsies of chelonian egg yolks.	2001 Jan	11161774
Androgenic anabolic steroids and arterial structure and function in male bodybuilders.	2001 Jan	11153743
Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene.	2001 Jan	11145749
Glucocorticoids regulate plasma membrane potential during rat thymocyte apoptosis in vivo and in vitro.	2001 Jan	11145606
Differential effects of dexamethasone treatment on lipopolysaccharide-induced testicular inflammation and reproductive hormone inhibition in adult rats.	2001 Jan	11139783
Regulation of cytochrome P450 aromatase gene expression in adult rat Leydig cells: comparison with estradiol production.	2001 Jan	11139774
The female-to-male transsexual patient: a source of human ovarian cortical tissue for experimental use.	2001 Jan	11139553
Sex steroid hormones enhance immune function in male and female Siberian hamsters.	2001 Jan	11124153
Heat-shock factor-1, steroid hormones, and regulation of heat-shock protein expression in the heart.	2001 Jan	11123263
Effects of hyperprolactinemia on rat prostate growth: evidence of androgeno-dependence.	2001 Jan	11120666
Chlorinated hydrocarbons and biomarkers of exposure in wading birds and fish of the lower Rio Grande Valley, Texas.	2001 Jan	11116345
Novel approaches to female sexual dysfunction.	2001 Jan	11116282
Inhibitors of type II 17beta-hydroxysteroid dehydrogenase.	2001 Jan 22	11165020
Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy.	2001 Jan 9	11148232

Patents

Sample Use Guides

In Vivo Use Guide

Starting dose of testosterone gel is 50 mg of testosterone (4 pump actuations, two 25 mg packets, or one 50 mg packet), applied once daily in the morning.

Route of Administration: Topical

In Vitro Use Guide

10 nM Testosterone significantly reduced secretion of BDNF in in human airway smooth muscle

Name

Type

Language

Testosterone propionate

Common Name

English

TESTOSTERONE PROPIONATE [JAN]

Common Name

English

TESTOSTERONE PROPIONATE [USP IMPURITY]

Common Name

English

TESTOSTERONE PROPIONATE [MART.]

Common Name

English

VIRORMONE

Common Name

English

TESTOSTERONE PROPIONATE [GREEN BOOK]

Common Name

English

TESTOSTERONE 17.BETA.-PROPIONATE

Common Name

English

TESTOSTERONE PROPIONATE [ORANGE BOOK]

Common Name

English

ORCHISTERONE

Common Name

English

TESTOSTERONI PROPIONAS [WHO-IP LATIN]

Common Name

English

TESTOSTERON 17-PROPIONATE

Common Name

English

ANDROST-4-EN-3-ONE, 17-(1-OXOPROPOXY)-, (17.BETA.)-

Systematic Name

English

TESTOSTERONE PROPIONATE [WHO-IP]

Common Name

English

TESTOSTERONE PROPIONATE [VANDF]

Common Name

English

TESTOSTERONE PROPIONATE CIII

Common Name

English

Testosterone propionate [WHO-DD]

Common Name

English

TESTOSTERONE PROPIONATE [USP MONOGRAPH]

Common Name

English

NSC-9166

Code

English

NRB-03689

Code

English

TESTOSTERONE PROPIONATE [MI]

Common Name

English

TESTOSTERONE PROPIONATE [EP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 522.842