Guggulsterone

Guggulsterone

E-Guggulsterone
Z-Guggulsterone
Names
IUPAC name (8R,9S,10R,13S,14S)-17-Ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione
Other names Pregna-4,17-diene-3,16-dione
Identifiers
CAS Number	95975-55-6 Y 39025-24-6 (E) Y 39025-23-5 (Z) Y
3D model (JSmol)	(E): Interactive image (Z): Interactive image
ChEMBL	ChEMBL410683 N
ChemSpider	4944297 (E) N 4952892 (Z) N
ECHA InfoCard	100.118.937
IUPHAR/BPS	2745
PubChem CID	6439929 (E) 6450278 (Z)
UNII	A4PW148END Y 9B259YE66O (E) Y 6CST3U34GN (Z) Y
CompTox Dashboard (EPA)	DTXSID6033538
InChI (E): InChI=1S/C21H28O2/c1-4-16-19(23)12-18-15-6-5-13-11-14(22)7-9-20(13,2)17(15)8-10-21(16,18)3/h4,11,15,17-18H,5-10,12H2,1-3H3/b16-4-/t15-,17+,18+,20+,21-/m1/s1 Key: WDXRGPWQVHZTQJ-AUKWTSKRSA-N (Z): InChI=1S/C21H28O2/c1-4-16-19(23)12-18-15-6-5-13-11-14(22)7-9-20(13,2)17(15)8-10-21(16,18)3/h4,11,15,17-18H,5-10,12H2,1-3H3/b16-4+/t15-,17+,18+,20+,21-/m1/s1 Key: WDXRGPWQVHZTQJ-OSJVMJFVSA-N
SMILES (E): O=C1C[C@@]2([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])CC[C@]2(C)/C1=C\C)=O (Z): O=C1C[C@@]2([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])CC[C@]2(C)/C1=C/C)=O
Properties
Chemical formula	C21H28O2
Molar mass	312.453 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Guggulsterone is a phytosteroid found in the resin of the guggul plant, Commiphora mukul. Guggulsterone can exist as either of two stereoisomers, E-guggulsterone and Z-guggulsterone. In humans, it acts as an antagonist of the farnesoid X receptor, which was once believed to result in decreased cholesterol synthesis in the liver. Several studies have been published that indicate no overall reduction in total cholesterol occurs using various dosages of guggulsterone, and levels of low-density lipoprotein ("bad cholesterol") increased in many people.^[1][2] Nevertheless, guggulsterone is an ingredient in many nutritional supplements. Guggulsterone was also found to have interactions with the viral Adipose Ribose Phosphatase enzyme of SARS-CoV2 and can prove to be a potential candidate for the development of therapeutics for the treatment of COVID19.^[3]

Guggulsterone is a broad-spectrum ligand of steroid hormone receptors, and is known to possess the following activities:^[4][5][6][7]

• Mineralocorticoid receptor antagonist (K_i = 39 nM)
• Progesterone receptor partial agonist (K_i = 201 nM)
• Glucocorticoid receptor antagonist (K_i = 224 nM)
• Androgen receptor antagonist (K_i = 240 nM)
• Estrogen receptor agonist (K_i > 5 μM; EC₅₀ > 5 μM)
• Farnesoid X receptor antagonist (IC₅₀ = 5–50 μM)
• Pregnane X receptor agonist (EC₅₀ = 2.4 μM ((Z)-isomer))

Guggulsterone has been found in animal research to be orally active; it has an absolute bioavailability of 42.9% after oral administration in rats, with a half-life of around 10 hours in this species, indicating a good pharmacokinetic profile.^[8]

References