11-Ketoprogesterone

11-Ketoprogesterone
Clinical data
Trade names	Ketogestin
Other names	Bio 66; U-1258; 11-Oxoprogesterone; Pregn-4-ene-3,11,20-trione
Identifiers
	IUPAC name (8S,9S,10R,13S,14S,17S)-17-Acetyl-10,13-dimethyl-2,6,7,8,9,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-3,11-dione;
CAS Number	516-15-4;
PubChem CID	94166;
ChemSpider	84982;
UNII	9Y1Y86O4T5;
ChEMBL	ChEMBL284253;
CompTox Dashboard (EPA)	DTXSID101031475 ;
ECHA InfoCard	100.007.476
Chemical and physical data
Formula	C21H28O3
Molar mass	328.452 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC(=O)[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C;
	InChI InChI=1S/C21H28O3/c1-12(22)16-6-7-17-15-5-4-13-10-14(23)8-9-20(13,2)19(15)18(24)11-21(16,17)3/h10,15-17,19H,4-9,11H2,1-3H3/t15-,16+,17-,19+,20-,21+/m0/s1; Key:WKAVAGKRWFGIEA-DADBAOPHSA-N;

11-Ketoprogesterone (brand name Ketogestin; former developmental code names Bio 66, U-1258), or 11-oxoprogesterone, also known as pregn-4-ene-3,11,20-trione, is a pregnane steroid related to cortisone (11-keto-17α,21-dihydroxyprogesterone) that was formerly used in veterinary medicine in the treatment of bovine ketosis.^[1] It was synthesized in 1940.^[1] The steroid has profound effects on carbohydrate metabolism and possesses activities associated with adrenal cortex hormones like cortisone.^[2] However, it is non-toxic even in high dosages, suggesting that it lacks conventional glucocorticoid activity, and it does not possess mineralocorticoid activity, unlike other adrenocortical hormones.^[2] 11-Ketoprogesterone may act through membrane glucocorticoid receptors.^[3]

11-Ketoprogesterone is reportedly devoid of androgenic, estrogenic, and progestogenic activity.^[2]^[4] 11β-Hydroxyprogesterone has also been reported to be devoid of progestogenic activity, but has subsequently been reported to possess about 1% of the progestogenic activity of progesterone.^[5] A halogenated derivative of 11-ketoprogesterone, 9α-bromo-11-ketoprogesterone, possesses relatively high progestogenic activity.^[5] Similarly to 11α-hydroxyprogesterone and 11β-hydroxyprogesterone, 11-ketoprogesterone is reported to act as an inhibitor of the enzyme 11β-hydroxysteroid dehydrogenase.^[6] It has also been found to act as a weak negative allosteric modulator of the GABA_A receptor.^[7]

References

^ ^a ^b Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 1014–. ISBN 978-1-4757-2085-3.
^ ^a ^b ^c Veterinary Medicine. American Veterinary Publishing Company. 1953. Experimentally, it is reported that ketogestin has a profound effect upon carbohydrate metabolism, accelerating production of glucose from protein (gluconegenesis). It possesses physiological activities associated with certain hormones of the adrenal cortex. Its effect on carbohydrate metabolism is similar to that of cortisone, as proved by deposition of glycogen, increasing glycosuria, and decreasing fat metabolism. This compound, however, does not cause certain undesirable activities in ketosis and other conditions as do other adrenocortical hormones, in that it does not cause retention of the sodium ion, nor does it produce hypertension during high sodium ion intake. Ketogestin is devoid of androgenic, estrogenic, or progestational activity and is nontoxic in amounts greatly exceeding pharmacological dosage.
^ Harrison RW, Balasubramanian K, Yeakley J, Fant M, Svec F, Fairfield S (1979). "Heterogeneity of AtT-20 Cell Glucocorticoid Binding Sites: Evidence for a Membrane Receptor". Steroid Hormone Receptor Systems. Advances in Experimental Medicine and Biology. Vol. 117. Springer. pp. 423–440. doi:10.1007/978-1-4757-6589-2_23. ISBN 978-1-4757-6591-5. PMID 474288.
^ Kincl FA (22 October 2013). "Copulatory Reflix Response to Steroids". In Dorfman RI (ed.). Steroidal Activity in Experimental Animals and Man. Elsevier Science. pp. 482–. ISBN 978-1-4832-7299-3.
^ ^a ^b Otto Hoffmann-Ostenhof (1959). Proceedings of the Fourth International Congress of Biochemistry, Vienna, 1-6 September, 1958. and. p. 269. In addition, it had been previously reported that 11β-hydroxyprogesterone was devoid of progestational action. However, we found that it does possess about 1% of the activity of progesterone. This trace activity is substantially enhanced by fluorination, since 9α-fluoro-11β-hydroxyprogesterone is eight times as active as the non-halogenated analogue.6 Concomitantly, Fried et al.7 described the relatively high progestational activity of 9α-bromo-11-ketoprogesterone as well.
^ Piwien-Pilipuk G, Galigniana MD (February 2000). "Oxidative stress induced by L-buthionine-(S,R)-sulfoximine, a selective inhibitor of glutathione metabolism, abrogates mouse kidney mineralocorticoid receptor function". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1495 (3): 263–280. doi:10.1016/s0167-4889(99)00166-4. PMID 10699465.
^ Zhong Y, Simmonds MA (1996). "Pharmacological characterisation of multiple components in the enhancement by pregnanolone and propofol of [3H]flunitrazepam binding to GABAA receptors". Neuropharmacology. 35 (9–10): 1193–1198. doi:10.1016/s0028-3908(96)00056-1. PMID 9014134. S2CID 20839591.

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[Elks2014-1] Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 1014–. ISBN 978-1-4757-2085-3.

[VeterinaryMedicine1953-2] Veterinary Medicine. American Veterinary Publishing Company. 1953. Experimentally, it is reported that ketogestin has a profound effect upon carbohydrate metabolism, accelerating production of glucose from protein (gluconegenesis). It possesses physiological activities associated with certain hormones of the adrenal cortex. Its effect on carbohydrate metabolism is similar to that of cortisone, as proved by deposition of glycogen, increasing glycosuria, and decreasing fat metabolism. This compound, however, does not cause certain undesirable activities in ketosis and other conditions as do other adrenocortical hormones, in that it does not cause retention of the sodium ion, nor does it produce hypertension during high sodium ion intake. Ketogestin is devoid of androgenic, estrogenic, or progestational activity and is nontoxic in amounts greatly exceeding pharmacological dosage.

[HarrisonBalasubramanian1979-3] Harrison RW, Balasubramanian K, Yeakley J, Fant M, Svec F, Fairfield S (1979). "Heterogeneity of AtT-20 Cell Glucocorticoid Binding Sites: Evidence for a Membrane Receptor". Steroid Hormone Receptor Systems. Advances in Experimental Medicine and Biology. Vol. 117. Springer. pp. 423–440. doi:10.1007/978-1-4757-6589-2_23. ISBN 978-1-4757-6591-5. PMID 474288.

[Dorfman2013-4] Kincl FA (22 October 2013). "Copulatory Reflix Response to Steroids". In Dorfman RI (ed.). Steroidal Activity in Experimental Animals and Man. Elsevier Science. pp. 482–. ISBN 978-1-4832-7299-3.

[Hoffmann-Ostenhof1959-5] Otto Hoffmann-Ostenhof (1959). Proceedings of the Fourth International Congress of Biochemistry, Vienna, 1-6 September, 1958. and. p. 269. In addition, it had been previously reported that 11β-hydroxyprogesterone was devoid of progestational action. However, we found that it does possess about 1% of the activity of progesterone. This trace activity is substantially enhanced by fluorination, since 9α-fluoro-11β-hydroxyprogesterone is eight times as active as the non-halogenated analogue.6 Concomitantly, Fried et al.7 described the relatively high progestational activity of 9α-bromo-11-ketoprogesterone as well.

[pmid10699465-6] Piwien-Pilipuk G, Galigniana MD (February 2000). "Oxidative stress induced by L-buthionine-(S,R)-sulfoximine, a selective inhibitor of glutathione metabolism, abrogates mouse kidney mineralocorticoid receptor function". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1495 (3): 263–280. doi:10.1016/s0167-4889(99)00166-4. PMID 10699465.

[pmid9014134-7] Zhong Y, Simmonds MA (1996). "Pharmacological characterisation of multiple components in the enhancement by pregnanolone and propofol of [3H]flunitrazepam binding to GABAA receptors". Neuropharmacology. 35 (9–10): 1193–1198. doi:10.1016/s0028-3908(96)00056-1. PMID 9014134. S2CID 20839591.

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See also

References