Novel components of the human metabolome: the identification, characterization and anti-inflammatory activity of two 5-androstene tetrols.
Two natural 5-androstene steroid tetrols, androst-5-ene-3β,7β,16α,17β-tetrol (HE3177) and androst-5-ene-3α,7β,16α,17β-tetrol (HE3413), were discovered in human plasma and urine. These compounds had significant aqueous solubility, did not bind or transactivate steroid-binding nuclear hormone receptors, and were not immunosuppressive in murine mixed-lymphocyte studies. Both compounds appear to be metabolic end products, as they were resistant to primary and secondary metabolism. Both were orally bioavailable, and were very well tolerated in a two-week dose-intensive toxicity study in mice. Anti-inflammatory properties were found with exogenous administration of these compounds in rodent disease models of multiple sclerosis, lung injury, chronic prostatitis, and colitis.
Ahlem
Clarence N
CN
Harbor Biosciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USA. cahlem@harborbiosciences.com
Page
Theodore M
TM
Auci
Dominick L
DL
Kennedy
Michael R
MR
Mangano
Katia
K
Nicoletti
Ferdinando
F
Ge
Yu
Y
Huang
Yujin
Y
White
Steven K
SK
Villegas
Sonia
S
Conrad
Douglas
D
Wang
Angela
A
Reading
Christopher L
CL
Frincke
James M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000737:Androstenols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D008968:Molecular Conformation; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D011472:Prostatitis / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D012995:Solubility; D013237:Stereoisomerism; D055815:Young Adult
D000737:Androstenols; D000893:Anti-Inflammatory Agents; C557015:androst-5-ene-3,7,16,17-tetrol