Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C23H32O4 |
Molecular Weight | 372.4978 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 6 / 6 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC[C@H](C(=O)COC(C)=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CCC4=CC(=O)CC[C@]34C
InChI
InChIKey=VPGRYOFKCNULNK-ACXQXYJUSA-N
InChI=1S/C23H32O4/c1-14(24)27-13-21(26)20-7-6-18-17-5-4-15-12-16(25)8-10-22(15,2)19(17)9-11-23(18,20)3/h12,17-20H,4-11,13H2,1-3H3/t17-,18-,19-,20+,22-,23-/m0/s1
DescriptionCurator's Comment: description was created based on several sources, including
http://www.canineaddisonsinfo.com/Percorten_Florinef.html
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/veterinary/003782/WC500196487.pdf
Curator's Comment: description was created based on several sources, including
http://www.canineaddisonsinfo.com/Percorten_Florinef.html
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/veterinary/003782/WC500196487.pdf
Desoxycorticosterone pivalate (DOCP) is a mineralocorticoid hormone and an analog of desoxycorticosterone. DOCP is a long-acting ester of desoxycorticosterone acetate (DOCA) which is recognized as having the same qualitative effects as the natural mineralocorticoid hormone aldosterone. It’s used as Percorten-V for replacement therapy for the mineralocorticoid deficit in dogs with primary adrenocortical insufficiency. Percorten-V is only available in the U.S., Canada, Australia and recently, Denmark. Percorten was originally developed for the treatment of Addison's disease in humans but the demand for it decreased significantly once Florinef was available. Unaware that their product was being prescribed “off-label” for the treatment of canine Addison’s Disease and faced with a decreased demand for Percorten, the manufacturer *almost* discontinued production until the veterinary community rose up and voiced their distress. Field trials were run and the FDA approved the use of Percorten-V (the "v" is for veterinary). DOCP like other adrenocorticoid hormones is thought to act by controlling the rate of synthesis of proteins. It reacts with receptor proteins in the cytoplasm to form a steroid-receptor complex. This complex moves into the nucleus, where it binds to chromatin that result in genetic transcription of cellular DNA to messenger RNA. The steroid hormones appear to induce transcription and synthesis of specific proteins, which produce the physiologic effects seen after administration. The most important effect of DOCP is to increase the rate of renal tubular absorption of sodium. This effect is seen most intensely in the thick portion of the ascending limb of the loop of Henle. It also increases sodium absorption in the proximal convoluted tubule but this effect is less important in sodium retention. Chloride follows the sodium out of the renal tubule. Another important effect of DOCP is enhanced renal excretion of potassium. This effect is driven by the resorption of sodium that pulls potassium from the extracellular fluid into the renal tubules, thus promoting potassium excretion.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1994 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17132855 |
0.01 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Palliative | PERCORTEN V Approved UseFor use as replacement therapy for the mineralocorticoid deficit in dogs with primary adrenocortical insufficiency |
PubMed
Title | Date | PubMed |
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Corticotropin effects on blood pressure and fluid and electrolyte homeostasis in five strains of rats. | 1992 May |
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Baboon cytochrome P450c11 is encoded by more than one gene. | 2000 Nov |
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Deoxycorticosterone suppresses the effects of losartan in nitric oxide-deficient hypertensive rats. | 2000 Nov |
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Diagnosis of adrenal cortical dysfunction by liquid chromatography-tandem mass spectrometry. | 2001 Apr |
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Primary culture system of adrenocortical cells from dogs to evaluate direct effects of chemicals on steroidogenesis. | 2001 Aug 28 |
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Pathophysiology of modulation of local glucocorticoid levels by 11beta-hydroxysteroid dehydrogenases. | 2001 Dec |
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Arterial epidermal growth factor receptor expression in deoxycorticosterone acetate-salt hypertension. | 2001 Dec 1 |
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Irreversible binding and adrenocorticolytic activity of the DDT metabolite 3-methylsulfonyl-DDE examined in tissue-slice culture. | 2001 Feb |
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Disorders of mineralocorticoid synthesis. | 2001 Mar |
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Effects of 18-hydroxylated steroids on corticosteroid production by human aldosterone synthase and 11beta-hydroxylase. | 2001 Sep |
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Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. | 2002 Feb |
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The effect of amino-acid substitutions I112P, D147E and K152N in CYP11B2 on the catalytic activities of the enzyme. | 2002 Feb |
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Gene transfer of endothelial NO synthase and manganese superoxide dismutase on arterial vascular cell adhesion molecule-1 expression and superoxide production in deoxycorticosterone acetate-salt hypertension. | 2002 Feb 1 |
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A glucocorticoid-responsive mutant androgen receptor exhibits unique ligand specificity: therapeutic implications for androgen-independent prostate cancer. | 2002 May |
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Blood pressure effects of intravenous apomorphine in conscious deoxycorticosterone-acetate salt-hypertensive rats. | 2003 Dec |
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Ghrelin and growth hormone secretagogue receptor are expressed in the rat adrenal cortex: Evidence that ghrelin stimulates the growth, but not the secretory activity of adrenal cells. | 2003 Feb 11 |
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Tert-butyl hydroperoxide-mediated vascular responses in DOCA-salt hypertensive rats. | 2003 Jan |
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Effects of chronic quercetin treatment on antioxidant defence system and oxidative status of deoxycorticosterone acetate-salt-hypertensive rats. | 2004 Apr |
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Expression of cytochrome P450c17 and other steroid-converting enzymes in the rat kidney throughout the life-span. | 2004 Jun |
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The serotonin transporter is present and functional in peripheral arterial smooth muscle. | 2004 Jun |
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Reduced NOS3 phosphorylation mediates reduced NO/cGMP signaling in mesenteric arteries of deoxycorticosterone acetate-salt hypertensive rats. | 2004 May |
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The effect of Sutherlandia frutescens on steroidogenesis: confirming indigenous wisdom. | 2004 Nov |
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The adrenocortical tumor cell line NCI-H295R as an in vitro screening system for the evaluation of CYP11B2 (aldosterone synthase) and CYP11B1 (steroid-11beta-hydroxylase) inhibitors. | 2005 Aug |
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Molecular identity and gene expression of aldosterone synthase cytochrome P450. | 2005 Dec 9 |
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Mineralocorticoid receptors: distribution and activation. | 2005 Jan |
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Functional characterization of two novel point mutations in the CYP21 gene causing simple virilizing forms of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | 2005 Jan |
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Cyclo-oxygenase-2, endothelium and aortic reactivity during deoxycorticosterone acetate salt-induced hypertension. | 2005 May |
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NAD(P)H oxidase/nitric oxide interactions in peroxisome proliferator activated receptor (PPAR)alpha-mediated cardiovascular effects. | 2005 Nov 11 |
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Functional effects of genetic variants in the 11beta-hydroxylase (CYP11B1) gene. | 2006 Dec |
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Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms. | 2006 Feb |
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Three novel point mutations of the CYP21 gene detected in classical forms of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | 2006 Mar |
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Mineralocorticoid synthesis during the periovulatory interval in macaques. | 2006 Oct |
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In vivo effects of thyroid hormone, corticosteroids and prolactin on cell proliferation and apoptosis in the anterior intestine of the euryhaline mudskipper (Periophthalmus modestus). | 2006 Oct 4 |
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Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: Beneficial effects of mineralocorticoid receptor blocker. | 2007 Feb |
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The glucuronidation of Delta4-3-Keto C19- and C21-hydroxysteroids by human liver microsomal and recombinant UDP-glucuronosyltransferases (UGTs): 6alpha- and 21-hydroxyprogesterone are selective substrates for UGT2B7. | 2007 Mar |
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Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagents. | 2007 May |
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Quantitative determination of progesterones and corticosteroids in human urine using gas chromatography/mass spectrometry: application to pelvic organ prolapse patients. | 2008 Apr |
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Glucocorticoid receptor phosphorylation differentially affects target gene expression. | 2008 Aug |
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Depot-specific steroidogenic gene transcription in human adipose tissue. | 2008 Dec |
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Novel mutation in cytochrome P450c17 causes complete combined 17alpha-hydroxylase/17,20-lyase deficiency. | 2008 Feb |
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Effects of ACTH, dexamethasone, and adrenalectomy on 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system. | 2008 Feb |
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One single dose of etomidate negatively influences adrenocortical performance for at least 24h in children with meningococcal sepsis. | 2008 Jan |
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Real-time analysis of gene regulation by glucocorticoid hormones. | 2008 May |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C521
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6E0A168OB8
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1174001
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m4172
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5952
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DB06780
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Desoxycorticosterone acetate
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100000087757
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CHEMBL1200542
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C058404
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SUB01600MIG
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C65369
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ACTIVE MOIETY
SUBSTANCE RECORD