ZOPOLRESTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H12F3N3O3S
Molecular Weight	419.377
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC1=NN(CC2=NC3=C(S2)C=CC(=C3)C(F)(F)F)C(=O)C4=C1C=CC=C4

InChI

InChIKey=BCSVCWVQNOXFGL-UHFFFAOYSA-N

InChI=1S/C19H12F3N3O3S/c20-19(21,22)10-5-6-15-14(7-10)23-16(29-15)9-25-18(28)12-4-2-1-3-11(12)13(24-25)8-17(26)27/h1-7H,8-9H2,(H,26,27)

HIDE SMILES / InChI

Molecular Formula	C19H12F3N3O3S
Molecular Weight	419.377
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7929871 | https://www.ncbi.nlm.nih.gov/pubmed/14747227 | http://adisinsight.springer.com/drugs/800001173

Zopolrestat is a novel carboxylic acid aldose reductase inhibitor. It has been shown to normalize sorbitol, fructose, and myoinositol levels in sciatic nerve, lens, retina, and kidney in diabetic rats and to restore normal renal plasma flow in galactosemic rats. It is being evaluated as an aldose reductase inhibitor for the treatment of diabetic complications.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Aldose reductase 45 Target ID: CHEMBL1900 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1899452 \| https://newdrugapprovals.org/2014/08/18/zopolrestat/	Inhibitor 8504		3.1 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Diabetic complications 3 Sources: https://newdrugapprovals.org/2014/08/18/zopolrestat/ http://adisinsight.springer.com/drugs/800001173	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
7.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
14 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
23.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
44.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
74.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
84 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
122 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
136 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
108 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
168 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
167 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
196 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
167 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
168 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
154 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
256 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
267 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
281 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
256 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
267 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
100 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
208 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day multiple, oral dose: 1000 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
239 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
208 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
71 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
165 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
328 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
636 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1010 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2130 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2140 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2760 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1430 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2740 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2900 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3040 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2850 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
2790 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2000 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4370 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4380 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4360 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4280 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
4460 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1412 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
3646 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day multiple, oral dose: 1000 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
3720 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
3646 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
18.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
32.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
32.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
32.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
32.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
32.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
28.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
28.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
28.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
28.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
28.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
26.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
27.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day multiple, oral dose: 1000 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
30.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
27.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11847537/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZOPOLRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.22% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7929871/			ZOPOLRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7929871/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/7929871/	Sources: https://pubmed.ncbi.nlm.nih.gov/7929871/
1200 mg single, oral Highest studied dose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7929871/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/7929871/	Sources: https://pubmed.ncbi.nlm.nih.gov/7929871/
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14747227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14747227/	Disc. AE: Transaminases increased... AEs leading to discontinuation/dose reduction: Transaminases increased (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/14747227/

AEs

AE	Significance	Dose	Population
Transaminases increased	2% Disc. AE	500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14747227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14747227/

PubMed

Title	Date	PubMed
Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-κB and MAPK pathways.	2013-11-15	24021941
Aldose reductase inhibition suppresses airway inflammation.	2011-05-30	21334316
Aldose reductase and AGE-RAGE pathways: central roles in the pathogenesis of vascular dysfunction in aging rats.	2010-10	20670350
Polyol pathway impairs the function of SERCA and RyR in ischemic-reperfused rat hearts by increasing oxidative modifications of these proteins.	2010-07	20025885
Role of aldose reductase in the high glucose induced expression of fibronectin in human mesangial cells.	2010-07	19821053
[Effect of PKC signalling pathway and aldose reductase on expression of fibronectin induced by transforming growth factor-β1 in human mesangial cells].	2010-06	21055159
Elevated Serum Sorbitol and not Fructose in Type 2 Diabetic Patients.	2010-05-04	20520742
Inhibition of aldose reductase attenuates endotoxin signals in human non-pigmented ciliary epithelial cells.	2010-05	20138035
Inhibition of aldose reductase prevents growth factor-induced G1-S phase transition through the AKT/phosphoinositide 3-kinase/E2F-1 pathway in human colon cancer cells.	2010-04	20354121
Inhibition of aldose reductase prevents experimental allergic airway inflammation in mice.	2009-08-06	19657391
Cancer biomarker AKR1B10 and carbonyl metabolism.	2009-03-16	19028477
Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts.	2008-10-28	18957123
A 41-year-old man with polyarthritis and severe autonomic neuropathy.	2008-08	19209266
Endotoxin causes pulmonary hypertension by upregulating smooth muscle endothelin type-B receptors: role of aldose reductase.	2008-08	18091567
Merging the binding sites of aldose and aldehyde reductase for detection of inhibitor selectivity-determining features.	2008-06-20	18495158
Aldose reductase regulates hepatic peroxisome proliferator-activated receptor alpha phosphorylation and activity to impact lipid homeostasis.	2008-06-20	18445591
Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress.	2008-05	18326808
Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers.	2008-04-28	18325492
Contribution of polyol pathway to arteriolar dysfunction in hyperglycemia. Role of oxidative stress, reduced NO, and enhanced PGH(2)/TXA(2) mediation.	2007-11	17873009
Aldose reductase inhibition prevents endotoxin-induced uveitis in rats.	2007-10	17898287
The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient.	2007	18224243
Current concepts in targeted therapies for the pathophysiology of diabetic microvascular complications.	2007	18200803
Aldose reductase inhibitor zopolrestat restores allergic hyporesponsiveness in alloxan-diabetic rats.	2006-11-07	16979157
Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages.	2006-11	17174561
Expect the unexpected or caveat for drug designers: multiple structure determinations using aldose reductase crystals treated under varying soaking and co-crystallisation conditions.	2006-10-13	16952371
Aldose reductase regulates TGF-beta1-induced production of fibronectin and type IV collagen in cultured rat mesangial cells.	2006-04	16669970
A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners.	2005-10-06	16190759
[Effects of aldose reductase on the transforming growth factor-beta1-induced expression of fibronectin and collagen IV: experiment with cultured rat mesangial cells].	2005-07-13	16253186
[Effects of aldose reductase transfection on the proliferation of rat mesangial cells in vitro].	2005-07	16251047
Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.	2005-05-05	15857120
Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options.	2005-05	15814847
Aldose reductase pathway mediates JAK-STAT signaling: a novel axis in myocardial ischemic injury.	2005-05	15746188
[Effects of aldose reductase on the expression of fibronectin and collagen IV in cultured rat renal mesangial cells].	2005-03	15938830
Effects of inhibition of the polyol pathway during chronic peritoneal exposure to a dialysis solution.	2005-02	16048249
Interaction between the polyol pathway and non-enzymatic glycation on aortic smooth muscle cell migration and monocyte adhesion.	2004-12-10	15530506
Cardiac abnormalities in diabetic patients with neuropathy: effects of aldose reductase inhibitor administration.	2004-02	14747227
Interaction between the polyol pathway and non-enzymatic glycation on mesangial cell gene expression.	2004	15528949
Aldose reductase induced by hyperosmotic stress mediates cardiomyocyte apoptosis: differential effects of sorbitol and mannitol.	2003-10-03	12881532
High glucose augments the angiotensin II-induced activation of JAK2 in vascular smooth muscle cells via the polyol pathway.	2003-08-15	12777386
The response of antioxidant genes to hyperglycemia is abnormal in patients with type 1 diabetes and diabetic nephropathy.	2003-03	12606529
Substituted pyrrol-1-ylacetic acids that combine aldose reductase enzyme inhibitory activity and ability to prevent the nonenzymatic irreversible modification of proteins from monosaccharides.	2003-01-30	12540241
Hyperglycemia increases endothelial superoxide that impairs smooth muscle cell Na+-K+-ATPase activity.	2002-03	11832341
Aldose reductase activation is a key component of myocardial response to ischemia.	2002-02	11772943
[1,2,4]Triazino[4,3-a]benzimidazole acetic acid derivatives: a new class of selective aldose reductase inhibitors.	2001-12-06	11728182

Patents

Sample Use Guides

In Vivo Use Guide

500 mg or 1,000 mg daily (12 months)

Route of Administration: Oral

In Vitro Use Guide

Hearts from acute diabetic (Type I) and age-matched control rats were isolated and retrogradely perfused. Hearts had either control perfusion or exposure to 1 microM zopolrestat for 10 min, followed by 20 min of global ischemia and 60 min of reperfusion. Zopolrestat blunted the rise in [Na]i during ischemia in both diabetic hearts and non-diabetic hearts. The end-ischemic [Na]i was 21.3 +/- 2.6 mM in the zopolrestat treated diabetics and 25.9 +/- 2.3 in zopolrestat treated non-diabetics, versus 31.6 +/- 2.6 mM and 32.9 +/- 2.8 mM in the untreated diabetics and untreated non-diabetics, respectively, (P = 0.002). Similarly, the rise in [Ca]i at the end of ischemia was significantly reduced in zopolrestat treated diabetic and non-diabetic hearts (P = 0.005). Zopolrestat increased the activity of Na-,K(+)-ATPase in diabetic hearts under baseline conditions (11.70 +/- 0.95 versus 7.28 +/- 0.98 mumol/h/mg protein, P = 0.005) as well as during ischemia and reperfusion. Similar changes in Na+,K(+)-ATPase activity were also observed in non-diabetic hearts.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:28:54 GMT 2025` Edited by `admin` on `Mon Mar 31 21:28:54 GMT 2025`
Record UNII	1PV3S9WP3D
Record Status	`Validated (UNII)`
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Name

Type

Language

ZOPOLRESTAT

Official Name

English

ALOND

Preferred Name

English

zopolrestat [INN]

Common Name

English

3,4-Dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]-1-phthalazineacetic acid

Systematic Name

English

ZOPOLRESTAT [USAN]

Common Name

English

ZOPOLRESTAT [MI]

Common Name

English

1-PHTHALAZINEACETIC ACID, 3,4-DIHYDRO-4-OXO-3-((5-(TRIFLUOROMETHYL)-2-BENZOTHIAZOLYL)METHYL)-

Common Name

English

Zopolrestat [WHO-DD]

Common Name

English

CP-73850

Code

English

CP-73,850

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C72880