ASP-9521

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H26N2O3
Molecular Weight	330.4213
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

COC1=CC2=C(NC(=C2)C(=O)N3CCC(CC(C)(C)O)CC3)C=C1

InChI

InChIKey=OXSCPDKUZWPWFR-UHFFFAOYSA-N

InChI=1S/C19H26N2O3/c1-19(2,23)12-13-6-8-21(9-7-13)18(22)17-11-14-10-15(24-3)4-5-16(14)20-17/h4-5,10-11,13,20,23H,6-9,12H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C19H26N2O3
Molecular Weight	330.4213
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Approval Year

Targets

Targets

Primary Target	Pharmacology	Condition	Potency
Aldo-keto reductase family 1 member C3 2	Inhibitor 8,504		11.0 nM [IC50]

C_max

Value	Dose	Analyte	Population
913 ng/mL	30 mg single, oral	ASP-9521 plasma	Homo sapiens
3148 ng/mL	100 mg single, oral	ASP-9521 plasma	Homo sapiens
7033 ng/mL	300 mg single, oral	ASP-9521 plasma	Homo sapiens
13651 ng/mL	600 mg single, oral	ASP-9521 plasma	Homo sapiens
6634 ng/mL	100 mg 1 times / day multiple, oral	ASP-9521 plasma	Homo sapiens
2277 ng/mL	30 mg 1 times / day multiple, oral	ASP-9521 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
30745 ng × h/mL	30 mg single, oral	ASP-9521 plasma	Homo sapiens
98708 ng × h/mL	100 mg single, oral	ASP-9521 plasma	Homo sapiens
320369 ng × h/mL	300 mg single, oral	ASP-9521 plasma	Homo sapiens
539312 ng × h/mL	600 mg single, oral	ASP-9521 plasma	Homo sapiens
108693 ng × h/mL	100 mg 1 times / day multiple, oral	ASP-9521 plasma	Homo sapiens
41251 ng × h/mL	30 mg 1 times / day multiple, oral	ASP-9521 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
30.4 h	30 mg single, oral	ASP-9521 plasma	Homo sapiens
23.4 h	100 mg single, oral	ASP-9521 plasma	Homo sapiens
26.3 h	300 mg single, oral	ASP-9521 plasma	Homo sapiens
22.2 h	600 mg single, oral	ASP-9521 plasma	Homo sapiens

Substance Class	Chemical
Record UNII	AA79G37CPR
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

ASP-9521

Code

English

ASP 9521

Preferred Name

English

(4-(2-HYDROXY-2-METHYLPROPYL)-1-PIPERIDINYL)(5-METHOXY-1H-INDOL-2-YL)METHANONE

Systematic Name

English

ASP9521

Code

English

METHANONE, (4-(2-HYDROXY-2-METHYLPROPYL)-1-PIPERIDINYL)(5-METHOXY-1H-INDOL-2-YL)-

Systematic Name

English

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Code System

Code

Type

Description

SMS_ID

300000042376

PRIMARY

PUBCHEM

25210792

PRIMARY

FDA UNII

AA79G37CPR

PRIMARY

MANUFACTURER PRODUCT INFORMATION

ASP-9521

PRIMARY

MedKoo CAT NO: 205818; CAS NO: 1126084-37-4; Description: ASP9521 is a novel, selective, orally bioavailable inhibitor of 17.BETA.-hydroxysteroid dehydrogenase type 5 (17.BETA.HSD5AKR1C3). ASP9521 has demonstrated anti-tumour activity in in vitro and in vivo preclinical models. ASP9521 inhibited conversion of androstenedione (AD) into testosterone (T) by recombinant human or cynomolgus monkey AKR1C3 in a concentration-dependent manner (IC50,human: 11 nmol/L - IC50,monkey: 49 nmol/L). ASP9521 showed >100-fold selectivity for AKR1C3 over the isoform AKR1C2. In LNCaP-AKR1C3 cells, ASP9521 suppressed AD-dependent PSA production and cell proliferation. In patients with mCRPC, ASP9521 demonstrated dose-proportional increase in exposure over the doses evaluated, with an acceptable safety and tolerability profile. However, the novel androgen biosynthesis inhibitor showed no relevant evidence of clinical activity. (Last update: 11/18/2015).

NCI_THESAURUS

C133224

PRIMARY

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Related Record

Type

Details


					TV2EYN1WQC

ALDO-KETO REDUCTASE FAMILY 1 MEMBER C3

TARGET -> INHIBITOR

Qualification:

IC50

Amount:

11 NANOMOLAR (average)

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Related Record

Type

Details


					AA79G37CPR

ASP-9521

ACTIVE MOIETY

Comments:

Results: ASP9521 showed potent inhibitory effect on enzymatic conversion from AD to T by both human AKR1C3 and cynomolgus monkey homologues in a concentration-dependent manner, with IC50 values of 11 and 49 nmol/L, respectively ASP9521 suppressed both AD-dependent PSA production and cell proliferation in LNCaP cells exogenously expressing AKR1C3 in vitro. The bioavailability of ASP9521after oral administration of 1mg/kg were 30% and 78% in rat and dog, respectively. Furthermore, ASP9521 single oral administration of 3 mg/kg suppressed AD-induced intratumoral T production in CWR22R xenografted castrate nude mice, and this inhibitory effect was maintained for 24 h. In addition, ASP9521 was rapidly eliminated from plasma after oral administration while its intratumoral concentration remained high in tumors expressing AKR1C3.

Amount:

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SMILES

InChI

Approval Year

Targets

Cmax

AUC

T1/2

C_max

T_1/2