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Compound Detail

CHEMBL16

PHENYTOIN
💊 Approved Drug
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💊 Approved Drug
O=C1NC(=O)C(c2ccccc2)(c2ccccc2)N1

Basic Information

ChEMBL ID CHEMBL16
Name PHENYTOIN
Phase Approved
Structure Type MOL
InChI Key CXOFVDLJLONNDW-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Dilabid Dilantin Dilantin-125 Dilantin-30 Diphenylhydantoin Epamin Fenitoina Hydantol Lepitoin NSC-8722 Phentytoin Phenytoin +4 more
10
Targets
32
Activities
3
Assay Types
25
PK Parameters
20
Publications
16
Known Names
18
Indications
1
Mechanisms

Molecular Properties

252.3
MW (Da)
1.77
ALogP
2
HBA
2
HBD
58.2
PSA (Ų)
0.80
QED
0
Ro5 Violations
2
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1953
Availability Prescription
Chirality Achiral

Routes of Administration

Oral Parenteral

Flags

Black Box Warning Natural Product
USAN Stem -toin
USAN Year 1975

Extended Properties

Molecular Formula C15H12N2O2
MW 252.27
Aromatic Rings 2
Heavy Atoms 19
NP-Likeness -0.27

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Sodium channel alpha subunit blocker BLOCKER Sodium channel alpha subunit

Indications

Epilepsy Seizures Anxiety Dementia Depressive Disorder Schizophrenia Anemia, Sickle Cell Optic Neuritis Pancreatic Neoplasms Polyneuropathies Thalassemia Wounds and Injuries Anemia Cocaine-Related Disorders Immune System Diseases Leukemia Lymphoma Neuroblastoma

ATC Classification

N03AB02
phenytoin
Level 1: NERVOUS SYSTEM
Level 2: ANTIEPILEPTICS
N03AB52
phenytoin, combinations
Level 1: NERVOUS SYSTEM
Level 2: ANTIEPILEPTICS

Activity Summary

IC50 25 meas. best 6.07
Ki 5 meas. best 5.22
EC50 2 meas.

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Unchecked
CHEMBL612545
IC50 6.07 4.7657 860.0 7
Cytochrome P450 2C9
CHEMBL3397
Ki 5.22 5.11 6000.0 2
Sodium channel alpha subunits; brain (Types I, II, III)
CHEMBL2096682
IC50 4.73 4.73 18500.0 1
Voltage-gated L-type calcium channel
CHEMBL2095229
IC50 4.66 4.66 21900.0 1
Sodium channel protein type 2 subunit alpha
CHEMBL3399
IC50 4.66 4.66 22000.0 2
Sodium channel protein type 4 subunit alpha
CHEMBL2072
Ki 4.62 4.62 24000.0 1
Sodium channel alpha subunits; brain (Types I, II, III)
CHEMBL2095171
IC50 4.4 4.4 40000.0 5
Sodium channel protein type 5 subunit alpha
CHEMBL1980
IC50 4.31 4.31 49000.0 1
Sodium channel protein type 2 subunit alpha
CHEMBL4187
Ki 4.27 4.27 53370.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.0 4.0 100000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 0.37 mL.min-1.kg-1 Homo sapiens
CL 0.4 mL.min-1.kg-1 Homo sapiens
CL 0.57 mL.min-1.kg-1 Homo sapiens
CL 2.8 mL.min-1.kg-1 Canis lupus familiaris
CL 7.4 mL.min-1.kg-1 Rattus norvegicus
CL 7.9 mL.min-1.kg-1 Macaca
CL 1.2e-05 mL.min-1.g-1 Homo sapiens
CL - - Homo sapiens
CL 0.012 uL/min Homo sapiens
F 80.0 % Homo sapiens
F 90.0 % Homo sapiens
Fu 0.095 - Homo sapiens
Fu 0.081 - Rattus norvegicus
Fu 0.047 - Sus scrofa
Fu 0.114 - Macaca fascicularis
Fu 0.259 - Canis lupus familiaris
Fu 0.082 - Cavia porcellus
Fu 0.088 - Mus musculus
Fu 0.134 - Rattus norvegicus
Fu 0.1 - Rattus norvegicus
T1/2 0.05167 hr Mus musculus
T1/2 0.01333 hr Mus musculus
T1/2 0.025 hr Mus musculus
T1/2 0.5 hr Rattus norvegicus
T1/2 16.5 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Unchecked IC50 = 860.0 nM 6.07 Apparent IC50 value by [3H]batrachotoxinin-A-20-alpha-benzoate-binding test perf... 9719582
Cytochrome P450 2C9 Ki = 6000.0 nM 5.22 Binding affinity towards cytochrome P450 2C9 14761192
Unchecked IC50 = 9800.0 nM 5.01 Inhibition of human aquaporin 4 M23 isoform expressed in Xenopus laevis oocytes 18178093
Cytochrome P450 2C9 Ki = 10000.0 nM 5.0 Binding affinity was measured on Cytochrome P450 2C9 10956186
Sodium channel alpha subunits; brain (Types I, II, III) IC50 = 18500.0 nM 4.73 Inhibition of [3H]BTX binding to guinea pig voltage-dependent sodium channel 3016269
Unchecked IC50 = 21000.0 nM 4.68 Inhibition of veratridine-induced guanidine flux in cardiac voltage-gated sodium... 11170622
Sodium channel protein type 2 subunit alpha IC50 = 22000.0 nM 4.66 Inhibition of rat Nav1.2 channel expressed in chinese hamster CHL1610 cells at p... 19388676
Sodium channel protein type 2 subunit alpha IC50 = 22000.0 nM 4.66 Inhibition of rat Nav1.2 expressed in CHL1610 cells at -67 to -107 mV after 2 to... 24205976
Voltage-gated L-type calcium channel IC50 = 21900.0 nM 4.66 Inhibition of Cav1.2 current measured using QPatch automatic path clamp system i... 23812503
Sodium channel protein type 4 subunit alpha Ki = 24000.0 nM 4.62 Affinity for inactive human SkM1 sodium channel expressed in HEK293 cells 14998340
Sodium channel alpha subunits; brain (Types I, II, III) IC50 = 40000.0 nM 4.4 Inhibition of [3H]BTX-B binding to neurotoxin site 2 of sodium channel of rat ce... 7562939
Unchecked IC50 = 40000.0 nM 4.4 Displacement of [3H]batrachotoxin from neurotoxin site 2 of voltage-gated sodium... 20638856
Unchecked IC50 = 39810.72 nM 4.4 Displacement of [3H]-BTX-B from neuronal voltage-gated sodium channel in rat cer... 19346132
Unchecked IC50 = 40000.0 nM 4.4 Displacement of [3H]-BTX-B from neuronal voltage-gated sodium channel in rat cer... 19346132
Sodium channel alpha subunits; brain (Types I, II, III) IC50 = 40000.0 nM 4.4 Inhibition of binding to sodium channel of rat cerebral cortex 7932556
Unchecked IC50 = 40000.0 nM 4.4 Inhibition of [3H]BTX binding to cardiac voltage-gated sodium channel 11170622
Sodium channel alpha subunits; brain (Types I, II, III) IC50 = 40000.0 nM 4.4 Inhibition of [3H]BTX-B binding to Neuronal voltage-dependent sodium channel of ... 9046351
Sodium channel alpha subunits; brain (Types I, II, III) IC50 = 40000.0 nM 4.4 In vitro inhibition of [3H]-BTX-B binding to sodium channels in rat brain synapt... 2846842
Sodium channel alpha subunits; brain (Types I, II, III) IC50 = 40000.0 nM 4.4 In vitro inhibition of Voltage-gated sodium channel by the displacement of [3H]b... 10229624
Sodium channel protein type 5 subunit alpha IC50 = 49000.0 nM 4.31 Inhibition of sodium current measured using whole-cell patch clamp experiments i... 21300721

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 1381
- 10.6019/CHEMBL3885881 Rattus norvegicus 467
- 10.5281/zenodo.13943903 ADMET 85
31158845 10.1038/s41586-019-1291-3 ADMET 58
16190747 10.1021/jm050283b Rattus norvegicus 20
3599026 10.1021/jm00390a015 Mus musculus 20
16472241 10.2174/1570163043334794 Hepatotoxicity 18
23085104 10.1016/j.ejmech.2012.08.037 Mus musculus 18
20116140 10.1016/j.ejmech.2009.12.062 Mus musculus 18
2308142 10.1021/jm00165a007 Mus musculus 16
8691481 10.1021/jm950761q Mus musculus 16
- 10.1007/s00044-012-0271-z Mus musculus 15
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
33545637 10.1016/j.ejmech.2021.113222 Mus musculus 14
26519928 10.1016/j.ejmech.2014.01.010 Mus musculus 12
26970661 10.1016/j.bmc.2016.02.026 Mus musculus 12
23993970 10.1016/j.bmc.2013.07.029 Rattus norvegicus 12
23265873 10.1016/j.bmcl.2012.11.051 Rattus norvegicus 12
26241874 10.1016/j.ejmech.2015.07.017 Mus musculus 12
27597416 10.1016/j.ejmech.2016.08.032 NON-PROTEIN TARGET 12

Data from ChEMBL 36 via Core Engine