Compound Detail

CHEMBL436

TOLRESTAT

💊 Approved Drug

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💊 Approved Drug

COc1ccc2c(C(=S)N(C)CC(=O)O)cccc2c1C(F)(F)F

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL436
Name	TOLRESTAT
Phase	Approved
Structure Type	MOL
InChI Key	LUBHDINQXIHVLS-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

Alderase Alredase AY-27,773 AY-27773 Tolrestat

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

357.4

MW (Da)

3.56

ALogP

HBA

HBD

49.8

PSA (Å²)

0.85

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	1989
Availability	Withdrawn
Chirality	Achiral

Flags

Withdrawn

USAN Stem	-stat
USAN Year	1984

Extended Properties

Molecular Formula	C16H14F3NO3S
MW	357.35
Aromatic Rings	2
Heavy Atoms	24
NP-Likeness	-0.14

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Aldose reductase inhibitor	INHIBITOR	Aldo-keto reductase family 1 member B1	✓	✓

Indications

Diabetes Mellitus

ATC Classification

A10XA01

tolrestat

Level 1: ALIMENTARY TRACT AND METABOLISM

Level 2: DRUGS USED IN DIABETES

Drug Warnings

Withdrawn

hepatotoxicity

Hepatic necrosis

Country: Worldwide Year: 1996

Withdrawn

hepatotoxicity

Hepatic necrosis

Country: Worldwide Year: 1996

Withdrawn

hepatotoxicity

Hepatic necrosis

Country: Worldwide Year: 1996

Activity Summary

IC50 48 meas. best 8.7

Ki 2 meas. best 7.3

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Aldo-keto reductase family 1 member B1 CHEMBL2622	IC50	8.7	7.207	2.0	10
Aldo-keto reductase family 1 member B1 CHEMBL1900	IC50	8.0	7.5125	10.0	8
Aldo-keto reductase family 1 member B10 CHEMBL5983	IC50	7.94	7.4933	11.6	3
Homo sapiens CHEMBL372	IC50	7.82	7.82	15.0	1
Rattus norvegicus CHEMBL376	IC50	7.82	6.6967	15.0	3
Aldo-keto reductase family 1 member B1 CHEMBL4559	IC50	7.82	7.7133	15.0	3
Unchecked CHEMBL612545	IC50	7.7	7.2875	20.0	4
Aldo-keto reductase family 1 member B1 CHEMBL3081	IC50	7.48	7.4043	33.0	7
Aldo-keto reductase family 1 member B10 CHEMBL5983	Ki	7.3	7.3	50.0	1
Aldo-keto reductase family 1 member A1 CHEMBL2246	IC50	7.19	6.3467	65.0	3
Aldo-keto reductase family 1 member A1 CHEMBL4049	IC50	6.27	5.965	540.0	2
Aldo-keto reductase family 1 member A1 CHEMBL3871	IC50	5.92	5.92	1210.0	1
Aldo-keto reductase family 1 member C21 CHEMBL1075270	Ki	4.66	4.66	22000.0	1
Aldo-keto reductase family 1 member C21 CHEMBL1075270	IC50	4.32	4.32	48000.0	1

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Aldo-keto reductase family 1 member B1	IC50	=	2.0	nM	8.7	In vitro inhibition of Aldose reductase (AR) from rat lens (RL)	1956041
Aldo-keto reductase family 1 member B1	IC50	=	2.9	nM	8.54	Inhibitory activity measured against rat lens aldose reductase using 3-pyridinec...	1900532
Aldo-keto reductase family 1 member B1	IC50	=	10.0	nM	8.0	Inhibition of N-terminal 6His-tagged human aldose reductase expressed in Escheri...	20304656
Aldo-keto reductase family 1 member B1	IC50	=	10.0	nM	8.0	Inhibition of human AKR1B1 assessed as decrease in glyceraldehyde reduction	28976752
Aldo-keto reductase family 1 member B10	IC50	=	11.6	nM	7.94	Inhibition of retinaldehyde reductase activity of human AKR1B10	18087047
Aldo-keto reductase family 1 member B1	IC50	=	13.0	nM	7.89	In vitro inhibition of recombinant human aldose reductase expressed in Escherich...	15857120
Rattus norvegicus	IC50	=	15.0	nM	7.82	Inhibition of galactitol accumulation in rat RBC incubated in presence of 50 mM ...	1908522
Homo sapiens	IC50	=	15.0	nM	7.82	Compound was tested for the inhibition of sorbitol accumulation in washed human ...	1899452
Aldo-keto reductase family 1 member B1	IC50	=	15.0	nM	7.82	In vitro inhibitory activity against aldose reductase in porcine lens.	9767647
Aldo-keto reductase family 1 member B1	IC50	=	16.0	nM	7.8	Inhibitory concentration against porcine lens aldose reductase (AR) with DL-glyc...	-
Unchecked	IC50	=	20.0	nM	7.7	Inhibitory activity on sorbital accumulation in human retinal cells was determin...	14613323
Aldo-keto reductase family 1 member B1	IC50	=	23.9	nM	7.62	Compound was evaluated In vitro for inhibition of aldose reductase activity by 5...	8027986
Unchecked	IC50	=	27.2	nM	7.57	Compound was evaluated In vitro for inhibition of aldose reductase activity by 5...	8027986
Aldo-keto reductase family 1 member B1	IC50	=	30.0	nM	7.52	Inhibition of aldose reductase from pig lenses	15456251
Aldo-keto reductase family 1 member B1	IC50	=	33.0	nM	7.48	In vitro inhibition of aldose reductase in partially purified bovine lens prepar...	1901912
Aldo-keto reductase family 1 member B1	IC50	=	33.0	nM	7.48	In vitro inhibition of aldose reductase activity in a partially purified bovine ...	8027986
Aldo-keto reductase family 1 member B1	IC50	=	34.0	nM	7.47	inhibition of aldose reductase activity was measured on partially purified bovin...	1908522
Aldo-keto reductase family 1 member B1	IC50	=	35.0	nM	7.46	Inhibitory activity against aldose reductase enzyme	12540241
Aldo-keto reductase family 1 member B1	IC50	=	35.0	nM	7.46	In vitro inhibition of bovine lens aldose reductase	2539477
Aldo-keto reductase family 1 member B1	IC50	=	35.0	nM	7.46	In vitro inhibition of aldose reductase from the partially purified bovine lens	2120443

Literature References

PubMed	DOI	Target Context	# Activities
12672241	10.1021/jm030762f	Rattus norvegicus	22
11728182	10.1021/jm0109210	Rattus norvegicus	22
19962793	10.1016/j.ejmech.2009.11.031	Rattus norvegicus	20
15646539	10.1016/s0399-8320(04)95062-2	Unchecked	11
18452283	10.1021/jm701613h	Rattus norvegicus	11
1908522	10.1021/jm00112a029	Rattus norvegicus	10
15646539	10.1016/s0399-8320(04)95062-2	NON-PROTEIN TARGET	8
8027986	10.1021/jm00039a017	Rattus norvegicus	6
2509709	10.1021/jm00131a012	Rattus norvegicus	5
2120443	10.1021/jm00172a034	Rattus norvegicus	5
10737739	10.1021/jm990168z	Unchecked	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
2120443	10.1021/jm00172a034	Aldo-keto reductase family 1 member B1	4
1956041	10.1021/jm00115a011	Aldo-keto reductase family 1 member B1	3
20304656	10.1016/j.bmc.2010.02.050	Unchecked	3
1469692	10.1021/jm00102a016	Rattus norvegicus	3
19121944	10.1016/j.bmc.2008.12.024	Unchecked	3
2509709	10.1021/jm00131a012	Aldo-keto reductase family 1 member B1	2
1908522	10.1021/jm00112a029	Aldo-keto reductase family 1 member B1	2
15857120	10.1021/jm0492094	Rattus norvegicus	2

Data from ChEMBL 36 via Core Engine