General
Preferred name
isotretinoin
Synonyms
ISOTRETINON ()
13-cis RA ()
13-cis-retinoic acid ()
13-cis retinoic acid ()
Accutane ()
Isotretinoine ()
Absorica ()
Claravis ()
Roaccutane ()
Retinoic acid 13-cis-form ()
Zenatane ()
RO-4-3780 ()
Retinoic acid, 13-cis- ()
Isotrex ()
Myorisan ()
Absorica ld ()
Isotretinoina ()
Vitamin a acid, 13-cis ()
RO 4-3780 ()
PAT-001 ()
13 Cis-Retinoic Acid ()
NSC-758156 ()
Sotret ()
Ro-43780 ()
Amnesteem ()
??13-cis-Retinoic Acid-d5 ()
P&D ID
PD001433
CAS
4759-48-2
97950-17-9
Tags
available
drug
Approved by
FDA
First approval
1982
Drug indication
Acne vulgaris
Coronavirus Disease 2019 (COVID-19)
Keratolytic
Drug Status
approved
withdrawn
Max Phase
4.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE Isotretinoin and its metabolites are conjugated and excreted in the urine and feces in similar amounts.[Label] 53-74% of an oral dose is eliminated as unchanged isotretinoin in the feces.[A179089]
PHARMACODYNAMICS The pharmacodynamics of isotretinoin are poorly understood.[Label]
MOA Isotretinoin produces its effects through altering progress through the cell cycle, cell differentiation, survival, and apoptosis.[A179091] These actions reduce sebum production, preventing the blockage of pores, and growth of acne causing bacteria.[A179091] Isotretinoin and 4-oxo-isotretinoin both significantly reduce the production of sebum.[A179091,Label] Isotretinoin has little to no affinity for retinol binding proteins (RBPs) and retinoic acid nuclear receptors (RARs).[A179091] Tretinoin and 4-oxo-tretinion bind to the RAR-γ receptor, which is suspected to be part of the action of acne treatment by isotretinoin.[A179091] Isotretinoin induces apoptosis in sebocytes, leading to a decrease in sebum production.[A179091] Isotretinoin also reduces the formation of comedones by reducing hyperkeratinization through an unknown mechanism.[A179091] Isotretinoin does not directly kill bacteria but it does reduce the size of sebum ducts and makes the microenvironment less hospitable to acne causing bacteria.[A179091] It may also increase immune mechanisms and alter chemotaxis of monocytes to reduce inflammation.[A179091]; ; There is preliminary evidence suggesting isotretinoin may interact with FoxO1, which may explain a substantial number of isotretinoin's unexplained actions.[A179122]
INDICATION Isotretinoin is indicated to treat severe recalcitrant nodular acne and patients ≥12 years enrolled in the iPLEDGE program.[Label,L6579]
METABOLISM Isotretinoin, or 13-cis-retinoic acid can undergo reversible cis-trans isomerization to all-trans-retinoic acid.[A179116] Isotretinoin undergoes 4-hydroxylation to 4-hydroxy-13-cis-retinoic acid, which is oxidized to the main metabolite 4-oxo-13-cis-retinoic acid.[A179116,A179101]. All-trans-retinoic acid undergoes 4-hydroxylation to 4-hydroxy-all-trans-retinoic acid, which is oxidized to 4-oxo-all-trans-retinoic acid.[A179116] 4-oxo-13-cis-retinoic acid can undergo reversible cis-trans isomerization to 4-oxo-all-trans-retinoic acid.[A179116]
HALF-LIFE The half life ranges from 7-39 hours[L6589] with a mean elimination half life of 20 hours.[A179089] The half life of 4-oxo-13-cis-retinoic acid ranges from 17-50 hours with a mean elimination half life of 25 hours.[L6589]
ABSORPTION Patients reach a maximum concentration of 74-511ng/mL after 1-4 hours following a 100mg oral dose.[A179089] Isotretinoin is better absorbed with a high fat meal and bioavailability may change from one brand to another.[Label]; ; Following a 40mg oral dose, fasted subjects reached a maximum concentration of 314ng/mL in 2.9 hours with an area under the curve of 4055ng/mL\*hr.[Label] Subjects given a high fat meal and a 40mg oral doses reached a maximum concentration of 395ng/mL in 6.4 hours with an area under the curve of 6095ng/mL\*mL.[Label]
DESCRIPTION Isotretinoin is a retinoid type drug ie it is a vitamin A-like molecule. It is the endogenous agonist for retinoic acid receptors (RARs). (GtoPdb)
TOXICITY Patients experiencing an overdose may present with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia.[Label] These symptoms may rapidly resolve.[Label] Generally no treatment is required for these overdoses.[A179113]; ; The oral lowest dose causing toxic effect (TDLO) for children is 30mg/kg/21W, oral TDLO for men is 24mg/kg/4W, oral TDLO for women is 56mg/kg/8W.[L6592] The intraperitoneal LD50 for rats is 901mg/kg, oral LD50 for mice is 3389mg/kg, oral LD50 for rats is >4000mg/kg.[L6592]; ; Isotretinoin is associated with major congenital malformations, spontaneous abortion, and premature birth.[Label] It is unknown if isotretinoin is expressed in breast milk but due to the associated hazards a decision should be made to either stop nursing or stop taking isotretinoin.[Label]; ; In animal studies, isotretinoin was associated with an increased risk of pheochromocytoma and adrenal medullary hyperplasia at doses above the recommended clinical dose.[Label] Isotretinoin was negative for the Ames test of mutagenicity once and weakly positive a second time.[Label] It has not been shown to be clastogenic.[Label] A study in dogs noted testicular atrophy after doses of 10-30 times the recommended clinical dose for 30 weeks.[Label] In trials with men there were no effects seen on sperm count, motility, morphology, ejaculate volume, and seminal plasma fructose.[Label]
DESCRIPTION Anti-inflammatory and antitumor actions mediated through RAR-beta and RAR-alpha receptors (LOPAC library)
Cell lines
1
Organisms
1
Compound Sets
26
AdooQ Bioactive Compound Library
A10485
Cayman Chemical Bioactives
21648
21855
ChEMBL Approved Drugs
CHEMBL547
ChEMBL Drugs
CHEMBL547
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB00982
DrugBank Approved Drugs
DB00982
DrugCentral
1508
DrugCentral Approved Drugs
1508
DrugMAP
DM4QTBN
DMBJTVL
DrugMAP Approved Drugs
DM4QTBN
Guide to Pharmacology
7600
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL547
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
CHEMBL547
Mcule NIBR MoA Box Subset
MCULE-9871118009
MedChem Express Bioactive Compound Library
HY-15127
NCATS Inxight Approved Drugs
EH28UP18IF
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NURSA ligand set
nursa/index.jsf?doi=10.1621%2FNDJZFRT4P4
Prestwick Chemical Library
Selleckchem Bioactive Compound Library
Isotretinoin
TargetMol Bioactive Compound Library
T1611
Withdrawn 2.0
w198
External IDs
58
Properties
(calculated by RDKit )
Molecular Weight
300.21
Hydrogen Bond Acceptors
1
Hydrogen Bond Donors
1
Rotatable Bonds
5
Ring Count
1
Aromatic Ring Count
0
cLogP
5.6
TPSA
37.3
Fraction CSP3
0.45
Chiral centers
0.0
Largest ring
6.0
QED
0.53
Structural alerts
2
aggregator (ZINC)
Aggregators
aggregator (Aggregator Advisor)
Aggregators
Related compounds
Custom attributes
(extracted from source data)
Selectivity
RAR-alpha, beta
Pathway
Metabolism
Autophagy
Metabolic Enzyme/Protease
Vitamin D Related/Nuclear Receptor
Target
RAR
RARA, RARB, RARG
Endogenous Metabolite
RAR/RXR
hydroxylase
MOA
Retinoid Receptor inhibitor
Retinoid RAR Agonists
Retinoid Receptor agonist
Member status
virtual
Indication
acne vulgaris (AV)
ATC
D10AD04
D10AD54
D10BA01
Toxicity type
reproductive
Therapeutic Class
Antiacne Agents
Antiviral Agents
Source data