Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 1.1.1.51 extracted from

  • Yepuru, M.; Wu, Z.; Kulkarni, A.; Yin, F.; Barrett, C.M.; Kim, J.; Steiner, M.S.; Miller, D.D.; Dalton, J.T.; Narayanan, R.
    Steroidogenic enzyme AKR1C3 is a novel androgen receptor-selective coactivator that promotes prostate cancer growth (2013), Clin. Cancer Res., 19, 5613-5625.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
R1881 requires amino acids 1-282 of AKR1C3 to elicit its coactivation, inhibitor GTx-560 requires the full-length AKR1C3 to bind and inhibit R1881-induced activity Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
AKR1C3, quantitative enzyme expression analysis by real-time PCR, recombinant expression in HEK-293 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information AKR1C3 siRNA reduces androgen receptor signaling in VCaP cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
GTx-560 competitively and selectively inhibits AKR1C3-dependent androgen receptor transactivation. GTx-560 completely blocks the formation of testosterone from androstenedione, indicating the ability of AKR1C3 inhibitors, unlike 5alpha-reductase inhibitors, to reduce testosterone levels Homo sapiens
additional information small-molecule inhibitors inhibit both the enzymatic and coactivator functions of AKR1C3 resulting in androgen-dependent prostate cancer and CRPC regression. No inhibition by indomethacin Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens AKR1C3 physically interacts with the androgen receptor ?
-
?
testosterone + NAD(P)+ Homo sapiens
-
androstenedione + NAD(P)H + H+
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens P42330
-
-

Source Tissue

Source Tissue Comment Organism Textmining
LNCaP cell
-
Homo sapiens
-
prostate cancer cell
-
Homo sapiens
-
VCaP cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information AKR1C3 physically interacts with the androgen receptor Homo sapiens ?
-
?
testosterone + NAD(P)+
-
Homo sapiens androstenedione + NAD(P)H + H+
-
r

Synonyms

Synonyms Comment Organism
AKR1C3
-
Homo sapiens
aldo keto reductase 1C3
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Homo sapiens
NADH
-
Homo sapiens
NADP+
-
Homo sapiens
NADPH
-
Homo sapiens

General Information

General Information Comment Organism
evolution the enzyme belongs to the AKR1C family Homo sapiens
malfunction AKR1C3 siRNA reduces androgen receptor signaling in VCaP cells. Small-molecule inhibitors inhibit both the enzymatic and coactivator functions of AKR1C3 resulting in androgen-dependent prostate cancer and CRPC regression Homo sapiens
physiological function castration-resistant prostate cancer may occur by several mechanisms including the upregulation of androgen receptor, coactivators, and steroidogenic enzymes, including aldo keto reductase 1C3 (AKR1C3). AKR1C3 converts weaker 17-keto androgenic precursors to more potent 17-hydroxy androgens and is consistently the major upregulated gene in castration-resistant prostate cancer, CRPC. AKR1C3 enhances androgen signaling and prostate cancer xenograft growth. AKR1C3 is a receptor- and tissue-selective pharmacologically targetable coactivator that promotes prostate cancer growth, AKR1C3-dependent R1881-induced androgen receptor transactivation in HEK-293 cells Homo sapiens