Identification

Name
Testosterone undecanoate
Accession Number
DB13946  (DBSALT001033)
Type
Small Molecule
Groups
Approved, Investigational
Description

Testosterone undecanoate is an esterified form of testosterone which is attached to a long fatty acid chain. The lack of a methylated site on the carbon 17 eliminates the adverse effects on the liver found in other testosterone analogs.[5] It is currently getting further developed to be an alternative to testosterone enanthate or testosterone cypionate by Paddock labs, and this new injectable has an FDA status of tentative approval. The original approval by the FDA of a product from testosterone undecanoate was done in 1953.

Structure
Thumb
Synonyms
  • Testosterone undeconate
  • Testosterone undecylate
External IDs
BAY 86-5037 / BRN 3176734 / CLR-610 / ORG 538 / ORG-538
Active Moieties
NameKindUNIICASInChI Key
Testosteroneprodrug3XMK78S47O58-22-0MUMGGOZAMZWBJJ-DYKIIFRCSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AndriolCapsule40 mgOralMerck Ltd.1992-12-31Not applicableCanada
AveedInjection250 mg/1mLIntramuscularEndo Pharmaceuticals Solutions Inc.2014-03-05Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PMS-testosteroneCapsule40 mgOralPharmascience Inc2009-10-08Not applicableCanada
Taro-testosteroneCapsule40 mgOralTaro Pharmaceuticals, Inc.2014-09-02Not applicableCanada
Categories
UNII
H16A5VCT9C
CAS number
5949-44-0
Weight
Average: 456.711
Monoisotopic: 456.360345406
Chemical Formula
C30H48O3
InChI Key
UDSFVOAUHKGBEK-CNQKSJKFSA-N
InChI
InChI=1S/C30H48O3/c1-4-5-6-7-8-9-10-11-12-28(32)33-27-16-15-25-24-14-13-22-21-23(31)17-19-29(22,2)26(24)18-20-30(25,27)3/h21,24-27H,4-20H2,1-3H3/t24-,25-,26-,27-,29-,30-/m0/s1
IUPAC Name
(1S,3aS,3bR,9aR,9bS,11aS)-9a,11a-dimethyl-7-oxo-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-1-yl undecanoate
SMILES
CCCCCCCCCCC(=O)O[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C

Pharmacology

Indication

Testosterone undecanoate is indicated as a testosterone replacement therapy in adult males that present conditions of deficiency or absence of endogenous testosterone. The approved conditions for the use of testosterone undecanoate are 1) primary hypogonadism, defined as a testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy or toxic damage from alcohol or heavy metals: or 2) hypogonadotropic hypogonadism caused by idiopathic gonadotropin or luteinizing hormone-releasing hormone deficiency or pituitary-hypothalamic injuries from tumors, trauma or radiation.[Label]

Associated Conditions
Pharmacodynamics

Clinical studies with testosterone undecanoate have shown a constant level of plasma testosterone over the weeks without falling on levels under the lower normal limit and briefly being over the normal upper limit. The levels of dihydrotestosterone and estradiol were suppressed but also remain within the normal limits. All these hormonal alterations remain stable even two weeks after the administration cease.[2]

Mechanism of action

The effects of testosterone in humans and other vertebrates occur by way of two primary mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of specific 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 5-alpha-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha-reductase. The T-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.[1]

TargetActionsOrganism
AAndrogen receptor
agonist
Human
UEstrogen receptor alphaNot AvailableHuman
UMineralocorticoid receptorNot AvailableHuman
Absorption

The absorption of testosterone undecanoate relies on the presence of fat as it is only soluble in it. Thus, the bioavailability of this testosterone derivative is very low of just 7%.[4] This highly lipophilic profile delineates the absorption of testosterone to be done via the lymphatic system.[5] The reported Cmax in steady state for testosterone undecanoate is 32 nmol/L after 7 days of administration.[2]

Volume of distribution

The distribution of testosterone undecanoate was limited to the liver, kidney and large and small intestine. Half of the administered dose remain near the injection site after 8 weeks of injection.[7] Following intravenous infusion of testosterone undecanoate, the reported volume of distribution was approximately 1 L/kg.[8]

Protein binding

Testosterone undecanoate is rapidly modified to form testosterone in plasma where 40% is bound to sex hormone-binding globulin and 2% remains unbound or bound to albumin and other proteins.[6]

Metabolism

To start its activity, testosterone undecanoate has to be processed by enzymes in the bloodstream. These enzymes will break the bond between the ester part of the molecule and the testosterone. Once separated, testosterone is metabolized to 17-keto steroids through two different pathways. The major active metabolites are estradiol and dihydrotestosterone (DHT). Testosterone is metabolized to DHT by steroid 5α-reductase in skin, liver and urogenital tract. In reproductive tissues, DHT is further metabolized to androstanediol.[6]

Route of elimination

About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form.[1] In the case of testosterone undecanoate, most of the administered dose is excreted in feces and to a lesser extent in the urine.[7]

Half life

The reported elimination half-life of testosterone undecanoate is very long and it ranges between 18-24 days.[3]

Clearance

After intravenous administration of testosterone undecanoate, the observed clearance rate was 24.5 ml min/kg. This clearance rate indicated a fast metabolic elimination and explained the low bioavailability of this derivate of testosterone.[4]

Toxicity

Preclinical trials have shown induction of uterine tumors as well as an increase in the susceptibility to hepatoma. Testosterone undecanoate is known to increase the number of tumors and differentiation of chemically induced carcinomas. Administration of exogenous testosterone reversibly suppresses spermatogenesis.[7]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
16-Bromoepiandrosterone16-Bromoepiandrosterone may increase the fluid retaining activities of Testosterone undecanoate.
19-norandrostenedione19-norandrostenedione may increase the fluid retaining activities of Testosterone undecanoate.
5-androstenedione5-androstenedione may increase the fluid retaining activities of Testosterone undecanoate.
AbciximabThe therapeutic efficacy of Abciximab can be increased when used in combination with Testosterone undecanoate.
AbirateroneThe serum concentration of Testosterone undecanoate can be increased when it is combined with Abiraterone.
AcarboseTestosterone undecanoate may increase the hypoglycemic activities of Acarbose.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Testosterone undecanoate.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Testosterone undecanoate.
AcetaminophenAcetaminophen may decrease the excretion rate of Testosterone undecanoate which could result in a higher serum level.
Acetyl sulfisoxazoleThe metabolism of Testosterone undecanoate can be decreased when combined with Acetyl sulfisoxazole.
Food Interactions
Not Available

References

General References
  1. Freeman ER, Bloom DA, McGuire EJ: A brief history of testosterone. J Urol. 2001 Feb;165(2):371-3. [PubMed:11176375]
  2. Saad F, Kamischke A, Yassin A, Zitzmann M, Schubert M, Jockenhel F, Behre HM, Gooren L, Nieschlag E: More than eight years' hands-on experience with the novel long-acting parenteral testosterone undecanoate. Asian J Androl. 2007 May;9(3):291-7. doi: 10.1111/j.1745-7262.2007.00275.x. [PubMed:17486268]
  3. Zhang GY, Gu YQ, Wang XH, Cui YG, Bremner WJ: A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men. J Androl. 1998 Nov-Dec;19(6):761-8. [PubMed:9876028]
  4. Tauber U, Schroder K, Dusterberg B, Matthes H: Absolute bioavailability of testosterone after oral administration of testosterone-undecanoate and testosterone. Eur J Drug Metab Pharmacokinet. 1986 Apr-Jun;11(2):145-9. [PubMed:3770015]
  5. Steroidal [Link]
  6. Steroidal [Link]
  7. FDA pharmacology reviews [Link]
  8. Pfizer monograph [Link]
External Links
ChemSpider
58664
ChEBI
135741
ChEMBL
CHEMBL2107067
Wikipedia
Testosterone_undecanoate
AHFS Codes
  • 68:08.00 — Androgens
FDA label
Download (517 KB)
MSDS
Download (45.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentTesticular Hypogonadism1
Not AvailableCompletedNot AvailableBone Density / Bone destruction / Hypogonadism / Paraplegia1
Not AvailableCompletedNot AvailableHypogonadism1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntramuscular250 mg/1mL
CapsuleOral40 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8338395No2006-02-272026-02-27Us
US7718640No2007-03-142027-03-14Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)64-64ºC'MSDS'
water solubilityInsoluble'MSDS'
Predicted Properties
PropertyValueSource
Water Solubility7.4e-05 mg/mLALOGPS
logP6.74ALOGPS
logP8.06ChemAxon
logS-6.8ALOGPS
pKa (Strongest Acidic)18.52ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.37 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity135.02 m3·mol-1ChemAxon
Polarizability57.8 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as steroid esters. These are compounds containing a steroid moiety which bears a carboxylic acid ester group.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid esters
Direct Parent
Steroid esters
Alternative Parents
Androgens and derivatives / 3-oxo delta-4-steroids / Delta-4-steroids / Cyclohexenones / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Steroid ester / Androgen-skeleton / Androstane-skeleton / 3-oxosteroid / 3-oxo-delta-4-steroid / Oxosteroid / Delta-4-steroid / Cyclohexenone / Ketone / Carboxylic acid ester
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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 ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Small EJ, Ryan CJ: The case for secondary hormonal therapies in the chemotherapy age. J Urol. 2006 Dec;176(6 Pt 2):S66-71. [PubMed:17084172]
  2. Omwancha J, Brown TR: Selective androgen receptor modulators: in pursuit of tissue-selective androgens. Curr Opin Investig Drugs. 2006 Oct;7(10):873-81. [PubMed:17086931]
  3. Petraki CD, Sfikas CP: Histopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma. Histol Histopathol. 2007 Jan;22(1):107-18. [PubMed:17128417]
  4. Maudsley S, Davidson L, Pawson AJ, Freestone SH, Lopez de Maturana R, Thomson AA, Millar RP: Gonadotropin-releasing hormone functionally antagonizes testosterone activation of the human androgen receptor in prostate cells through focal adhesion complexes involving Hic-5. Neuroendocrinology. 2006;84(5):285-300. Epub 2007 Jan 4. [PubMed:17202804]
  5. Lapauw B, Goemaere S, Crabbe P, Kaufman JM, Ruige JB: Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men? Eur J Endocrinol. 2007 Mar;156(3):395-401. [PubMed:17322500]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Kojima H, Iida M, Katsura E, Kanetoshi A, Hori Y, Kobayashi K: Effects of a diphenyl ether-type herbicide, chlornitrofen, and its amino derivative on androgen and estrogen receptor activities. Environ Health Perspect. 2003 Apr;111(4):497-502. [PubMed:12676605]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107066.575 Da
References
  1. Takeda AN, Pinon GM, Bens M, Fagart J, Rafestin-Oblin ME, Vandewalle A: The synthetic androgen methyltrienolone (r1881) acts as a potent antagonist of the mineralocorticoid receptor. Mol Pharmacol. 2007 Feb;71(2):473-82. Epub 2006 Nov 14. [PubMed:17105867]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
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]
  2. Zhang T, Zhu Y, Gunaratna C: Rapid and quantitative determination of metabolites from multiple cytochrome P450 probe substrates by gradient liquid chromatography-electrospray ionization-ion trap mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):371-9. [PubMed:12401364]
  3. Maenpaa J, Hall SD, Ring BJ, Strom SC, Wrighton SA: Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism: the effect of assay conditions and regioselective stimulation by alpha-naphthoflavone, terfenadine and testosterone. Pharmacogenetics. 1998 Apr;8(2):137-55. [PubMed:10022752]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  5. Source [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Sjoberg RL, Ducci F, Barr CS, Newman TK, Dell'osso L, Virkkunen M, Goldman D: A non-additive interaction of a functional MAO-A VNTR and testosterone predicts antisocial behavior. Neuropsychopharmacology. 2008 Jan;33(2):425-30. Epub 2007 Apr 11. [PubMed:17429405]
  2. Hoff KM: Interaction of testosterone with monoamineoxidase in mouse brain maturation. Gen Pharmacol. 1977;8(1):55-7. [PubMed:590724]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name
CYP11A1
Uniprot ID
P05108
Uniprot Name
Cholesterol side-chain cleavage enzyme, mitochondrial
Molecular Weight
60101.87 Da
References
  1. Kostic TS, Stojkov NJ, Bjelic MM, Mihajlovic AI, Janjic MM, Andric SA: Pharmacological doses of testosterone upregulated androgen receptor and 3-Beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase and impaired leydig cells steroidogenesis in adult rats. Toxicol Sci. 2011 Jun;121(2):397-407. doi: 10.1093/toxsci/kfr063. Epub 2011 Apr 6. [PubMed:21427060]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 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]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 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]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-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 oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-s...
Gene Name
CYP2A13
Uniprot ID
Q16696
Uniprot Name
Cytochrome P450 2A13
Molecular Weight
56687.095 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 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]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  3. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Monooxygenase activity
Specific Function
Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name
CYP3A43
Uniprot ID
Q9HB55
Uniprot Name
Cytochrome P450 3A43
Molecular Weight
57669.21 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]
Kind
Protein group
Organism
Not Available
Pharmacological action
No
Actions
Substrate
General Function
Electron carrier activity
Specific Function
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and andro...

Components:

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other/unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Pardridge WM: Serum bioavailability of sex steroid hormones. Clin Endocrinol Metab. 1986 May;15(2):259-78. [PubMed:3521955]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other/unknown
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Pardridge WM: Serum bioavailability of sex steroid hormones. Clin Endocrinol Metab. 1986 May;15(2):259-78. [PubMed:3521955]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Lu R, Kanai N, Bao Y, Wolkoff AW, Schuster VL: Regulation of renal oatp mRNA expression by testosterone. Am J Physiol. 1996 Feb;270(2 Pt 2):F332-7. [PubMed:8779895]
  2. Kanai N, Lu R, Bao Y, Wolkoff AW, Vore M, Schuster VL: Estradiol 17 beta-D-glucuronide is a high-affinity substrate for oatp organic anion transporter. Am J Physiol. 1996 Feb;270(2 Pt 2):F326-31. [PubMed:8779894]
  3. Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. [PubMed:8786566]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Kobayashi Y, Hirokawa N, Ohshiro N, Sekine T, Sasaki T, Tokuyama S, Endou H, Yamamoto T: Differential gene expression of organic anion transporters in male and female rats. Biochem Biophys Res Commun. 2002 Jan 11;290(1):482-7. [PubMed:11779196]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
References
  1. Kobayashi Y, Hirokawa N, Ohshiro N, Sekine T, Sasaki T, Tokuyama S, Endou H, Yamamoto T: Differential gene expression of organic anion transporters in male and female rats. Biochem Biophys Res Commun. 2002 Jan 11;290(1):482-7. [PubMed:11779196]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. [PubMed:9830022]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Katoh M, Nakajima M, Yamazaki H, Yokoi T: Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport. Eur J Pharm Sci. 2001 Feb;12(4):505-13. [PubMed:11231118]
  2. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Schroeder A, Eckhardt U, Stieger B, Tynes R, Schteingart CD, Hofmann AF, Meier PJ, Hagenbuch B: Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol. 1998 Feb;274(2 Pt 1):G370-5. [PubMed:9486191]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Tzvetkov MV, Vormfelde SV, Balen D, Meineke I, Schmidt T, Sehrt D, Sabolic I, Koepsell H, Brockmoller J: The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther. 2009 Sep;86(3):299-306. doi: 10.1038/clpt.2009.92. Epub 2009 Jun 17. [PubMed:19536068]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Tzvetkov MV, Vormfelde SV, Balen D, Meineke I, Schmidt T, Sehrt D, Sabolic I, Koepsell H, Brockmoller J: The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther. 2009 Sep;86(3):299-306. doi: 10.1038/clpt.2009.92. Epub 2009 Jun 17. [PubMed:19536068]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, van Veen HW: Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51. Epub 2003 Mar 28. [PubMed:12668685]

Drug created on January 11, 2018 16:11 / Updated on September 22, 2018 22:40