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| Cas No.: | 1126084-37-4 |
| Chemical Name: | [4-(2-Hydroxy-2-methylpropyl)piperidin-1-yl]-(5-methoxy-1H-indol-2-yl)methanone |
| Synonyms: | ASP9521;ASP-9521;ASP 9521;OXSCPDKUZWPWFR-UHFFFAOYSA-N;BCP20729;AK00792700;A14412;4-(2-Hydroxy-2-methylpropyl)piperidino(5-methoxy-1H-indole-2-yl)methanone;1-{1-[(5-methoxy-1H-indol-2-yl)carbonyl]piperidin-4-yl}-2-methylpropan-2-ol;1-{1-[(5-methoxy-1h-indol-2-yl)carbonyl] piperidin-4-yl}-2-methylpropan-2-ol;[4-(2-Hydroxy-2-methylpropyl)-1-piperidinyl](5-methoxy-1H-indol-2-yl)methanone;(4-(2-Hydroxy-2-methylpropyl)piperidin-1-yl)(5-methoxy;[4-(2-Hydroxy-2-methylpropyl)piperidin-1-yl]-(5-methoxy-1H-indol-2-yl)methanone;s6749;ASP9521; ASP 9521; AKR1C3 inhibitor ; 17HSD5 inhibitor;[4-(2-Hydroxy-2-methylpropyl)-1-piperidinyl](5-methoxy-1H-indo |
| SMILES: | O([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C1([H])C([H])([H])C([H])([H])N(C(C2=C([H])C3C([H])=C(C([H])=C([H])C=3N2[H])OC([H])([H])[H])=O)C([H])([H])C1([H])[H] |
| Formula: | C19H26N2O3 |
| M.Wt: | 330.4213 |
| Purity: | >98% |
| Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
| Description: | ASP-9521 is a potent, selective and orally available AKR1C3 inhibitor with an IC50 of 11 nM for human AKR1C3. |
| Target: | IC50:11 nM (human AKR1C3), 49 nM (monkey AKR1C3)[1] |
| In Vivo: | In CWR22R xenografts, single oral administration of ASP-9521 (3 mg/kg) inhibits AD-induced intratumoural T production and this inhibitory effect is maintained for 24 h. After oral administration, ASP-9521is rapidly eliminated from plasma, while its intratumoural concentration remained high. The bioavailability of ASP-9521 after oral administration (1 mg/kg) is 35 %, 78 % and 58 % in rats, dogs and monkeys, respectively[1]. |
| In Vitro: | AKR1C3 is a promising therapeutic target in castrationresistant prostate cancer, as combination of an AKR1C3 inhibitor and a gonadotropin-releasing hormone analogue may lead to complete androgen blockade.ASP-9521 inhibits conversion of androstenedione (AD) into androstenediol and testosterone (T) by recombinant human or cynomolgus monkey AKR1C3 in a concentrationdependent manner (IC50, human: 11 nM; IC50,monkey: 49 nM). ASP-9521 shows more than 100-fold selectivity for AKR1C3 over the isoform AKR1C2. In LNCaP-AKR1C3 cells, ASP-9521 suppresses AD-dependent PSA production and cell proliferation[1]. |
| Cell Assay: | LNCaP-AKR1C3 cells stably expressing human AKR1C3 are seeded in 96-well plates at 10000 cells/100 μL/well in RPMI-1640 medium supplemented with heat-inactivated charcoal-dextran-stripped FBS (1 % for the PSA expression assay and T measurement and 5 % for the cell proliferation assay). After 24 h incubation, AD is added to each well with or without ASP-9521 (0.3-100 nM). The cell culture media are collected 24 h after administration of AD to measure T concentration and 6 days after administration of AD to measure cell proliferation using Cell-Titer Glo assay[1]. |
| Animal Administration: | Mice carrying HEK293 or HEK293-AKR1C3 tumours with similar sizes are selected and randomly divided into 5 groups (N=3 for each group). All groups are treated with ASP-9521 (single oral administration; 3 mg/kg). Plasma (from the central vein) and tumour tissues are collected at 0.25, 0.5, 1, 2 and 4 h after administration of ASP-9521, and ASP-9521 concentrations are determined using the HPLCMS/MS method[1]. |
| References: | [1]. Kikuchi A, et al. In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5; AKR1C3).Invest New Drugs. 2014 Oct;32(5):860-70. |