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
Molecular Formula | C23H32O4 |
Molecular Weight | 372.4978 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 6 / 6 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
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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Extraadrenal expression of steroid 21-hydroxylase and 11 beta-hydroxylase by a benign testicular Leydig cell tumor. | 1991 Dec |
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19-Nor-deoxycorticosterone production from aldosterone-producing adenomas. | 1992 Apr |
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Myocardial performance of STZ-diabetic DOCA-hypertensive rats. | 1992 Dec |
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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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Reference values for urinary steroids in Japanese newborn infants: gas chromatography/mass spectrometry in selected ion monitoring. | 2003 Dec |
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Blood pressure effects of intravenous apomorphine in conscious deoxycorticosterone-acetate salt-hypertensive rats. | 2003 Dec |
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Endothelin-1 increases vascular superoxide via endothelin(A)-NADPH oxidase pathway in low-renin hypertension. | 2003 Feb 25 |
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Tert-butyl hydroperoxide-mediated vascular responses in DOCA-salt hypertensive rats. | 2003 Jan |
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Norbormide enhances late steps of steroid-hormone synthesis in rat and mouse adrenal cortex. | 2003 Mar |
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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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Do human vascular endothelial cells produce aldosterone? | 2004 Aug |
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Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism. | 2004 Jan |
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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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The regulation of aldosterone synthase expression. | 2004 Mar 31 |
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The human mineralocorticoid receptor only partially differentiates between different ligands after expression in fission yeast. | 2005 Apr |
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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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Adrenocortical carcinoma producing 11-deoxycorticosterone: a rare cause of mineralocorticoid hypertension. | 2005 Jan |
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11-deoxycorticosterone is a potent agonist of the rainbow trout (Oncorhynchus mykiss) mineralocorticoid receptor. | 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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Differential expression and function of beacon in the rat adrenal cortex and medulla. | 2005 Jul |
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The residue E351 is essential for the activity of human 21-hydroxylase: evidence from a naturally occurring novel point mutation compared with artificial mutants generated by single amino acid substitutions. | 2005 Jul |
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Role of activation function domain-1, DNA binding, and coactivator GRIP1 in the expression of partial agonist activity of glucocorticoid receptor-antagonist complexes. | 2005 Mar 8 |
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Cyclo-oxygenase-2, endothelium and aortic reactivity during deoxycorticosterone acetate salt-induced hypertension. | 2005 May |
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Biochemical characterization of the Arctic char (Salvelinus alpinus) ovarian progestin membrane receptor. | 2005 Nov 10 |
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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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Calcitonin gene-related peptide and hypertension. | 2005 Sep |
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Steroid signalling in the ovarian surface epithelium. | 2005 Sep |
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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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Design of an Escherichia coli system for whole cell mediated steroid synthesis and molecular evolution of steroid hydroxylases. | 2006 Jun 25 |
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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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Hydration of rainbow trout oocyte during meiotic maturation and in vitro regulation by 17,20{beta}-dihydroxy-4-pregnen-3-one and cortisol. | 2006 Mar |
|
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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[11beta-hydroxylase deficiency: improvement of final height with growth hormone and gonadotropin-releasing hormone analog]. | 2007 Aug |
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Evolution of the corticosteroid receptor signalling pathway in fish. | 2007 Aug-Sep |
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Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. | 2007 Feb |
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Concomitant secretion of glucocorticoid, androgens, and mineralocorticoid by an adrenocortical carcinoma: case report and review of literature. | 2007 Jul-Aug |
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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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Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone. | 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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Aldosterone synthase deficiency caused by a homozygous L451F mutation in the CYP11B2 gene. | 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 |
|
One single dose of etomidate negatively influences adrenocortical performance for at least 24h in children with meningococcal sepsis. | 2008 Jan |
|
Real-time analysis of gene regulation by glucocorticoid hormones. | 2008 May |
Patents
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:15:54 GMT 2023
by
admin
on
Fri Dec 15 15:15:54 GMT 2023
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Record UNII |
6E0A168OB8
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Record Status |
Validated (UNII)
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C521
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Desoxycorticosterone acetate
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100000087757
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C058404
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SUB01600MIG
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C65369
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