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 (Comment) | Organism |
---|---|
AKR1C3, quantitative enzyme expression analysis by real-time PCR, recombinant expression in HEK-293 cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | AKR1C3 siRNA reduces androgen receptor signaling in VCaP cells | Homo sapiens |
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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P42330 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
LNCaP cell | - |
Homo sapiens | - |
prostate cancer cell | - |
Homo sapiens | - |
VCaP cell | - |
Homo sapiens | - |
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 | Comment | Organism |
---|---|---|
AKR1C3 | - |
Homo sapiens |
aldo keto reductase 1C3 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Homo sapiens | |
NADH | - |
Homo sapiens | |
NADP+ | - |
Homo sapiens | |
NADPH | - |
Homo sapiens |
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 |