Details of the Drug

General Information of Drug (ID: DM8BKU9)

Drug Name

Acitretin

Synonyms

Acitretina; Acitretine; Acitretinum; Etretin; Isoacitretin; Isoetretin; Neotigason; Soriatane; TMMP; Acitretina [Spanish]; Acitretine [French]; Acitretinum [Latin]; Retinoid etretin; U0279; Ro 10-1670; Ro 13-7652; Soriatane (TN); Soriatane, Acitretin; Acitretin (USAN/INN); Acitretin [USAN:INN:BAN]; All-trans-Acitretin; Ro 10-1670/000; Ro-10-1670; Ro-13-7652; Ro-10-1670/000; All-trans-3,7-Dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonatetraenoic acid; (2E,4E,6E,8E)-3,7-dimethyl-9-[2,3,6-trimethyl-4-(methyloxy)phenyl]nona-2,4,6,8-tetraenoic acid; (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid; (all-E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid; 13-cis-Acitretin; 9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid; 9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid

Indication

Disease Entry	ICD 11	Status	REF
Psoriasis vulgaris	EA90	Approved	[1]
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Therapeutic Class

Keratolytic Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

326.4

Logarithm of the Partition Coefficient (xlogp)

6.1

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Bioavailability: 59% of drug becomes completely available to its intended biological destination(s) [3]
Elimination: 0% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 49 (range 33 - 96) hours [4]
Metabolism: The drug is metabolized via simple isomerization []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.82919 micromolar/kg/day [5]

Chemical Identifiers

Formula: C21H26O3
IUPAC Name: (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid
Canonical SMILES: CC1=CC(=C(C(=C1/C=C/C(=C/C=C/C(=C/C(=O)O)/C)/C)C)C)OC
InChI: InChI=1S/C21H26O3/c1-14(8-7-9-15(2)12-21(22)23)10-11-19-16(3)13-20(24-6)18(5)17(19)4/h7-13H,1-6H3,(H,22,23)/b9-7+,11-10+,14-8+,15-12+
InChIKey: IHUNBGSDBOWDMA-AQFIFDHZSA-N

Cross-matching ID

PubChem CID: 5284513
ChEBI ID: CHEBI:50173
CAS Number: 55079-83-9
DrugBank ID: DB00459
TTD ID: D05QDC
VARIDT ID: DR00827
ACDINA ID: D00012

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Signal transducer and activator of transcription 3 (STAT3)	TTH8FZW	STAT3_HUMAN	Inhibitor	[6]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[7]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[8]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[9]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Gene/Protein Processing	[9]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Gene/Protein Processing	[10]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Gene/Protein Processing	[9]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Gene/Protein Processing	[11]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Gene/Protein Processing	[11]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Gene/Protein Processing	[11]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Psoriasis vulgaris

ICD Disease Classification

EA90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Signal transducer and activator of transcription 3 (STAT3)	DTT	STAT3	6.50E-03	-0.12	-0.21

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Acitretin

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Verteporfin	DMIY6DB	Moderate	Increased risk of photosensitivity reactions by the combination of Acitretin and Verteporfin.	Psoriasis [EA90]	[12]
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Coadministration of a Drug Treating the Disease Different from Acitretin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[13]
Tretinoin	DM49DUI	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and Tretinoin.	Acne vulgaris [ED80]	[12]
Isotretinoin	DM4QTBN	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and Isotretinoin.	Acne vulgaris [ED80]	[12]
Sarecycline	DMLZNIQ	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and Sarecycline .	Acne vulgaris [ED80]	[14]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[15]
Oxytetracycline	DMOVH1M	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and Oxytetracycline.	Bacterial infection [1A00-1C4Z]	[14]
Omadacycline	DMR2J95	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and Omadacycline.	Bacterial infection [1A00-1C4Z]	[14]
Minocycline	DMVN5OH	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and Minocycline.	Bacterial infection [1A00-1C4Z]	[14]
Tetracycline	DMZA017	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and Tetracycline.	Bacterial infection [1A00-1C4Z]	[14]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Acitretin and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[16]
Demeclocycline	DMZEPFJ	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and Demeclocycline.	Bronchitis [CA20]	[14]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Cannabidiol.	Epileptic encephalopathy [8A62]	[12]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[17]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[18]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Acitretin and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[19]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Acitretin and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[20]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Acitretin and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[21]
TP-434	DM5A31S	Major	Increased risk of pseudotumor cerebri by the combination of Acitretin and TP-434.	Infectious gastroenteritis/colitis [1A40]	[14]
Methotrexate	DM2TEOL	Major	Increased risk of hepatotoxicity by the combination of Acitretin and Methotrexate.	Leukaemia [2A60-2B33]	[20]
Porfimer Sodium	DM7ZWNY	Moderate	Increased risk of photosensitivity reactions by the combination of Acitretin and Porfimer Sodium.	Lung cancer [2C25]	[22]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[23]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Idelalisib.	Mature B-cell leukaemia [2A82]	[24]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Clofarabine.	Mature B-cell lymphoma [2A85]	[25]
Methoxsalen	DME8FZ9	Moderate	Increased risk of photosensitivity reactions by the combination of Acitretin and Methoxsalen.	Mycosis fungoides [2B01]	[13]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Acitretin and Leflunomide.	Rheumatoid arthritis [FA20]	[20]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[12]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Acitretin and Naltrexone.	Substance abuse [6C40]	[26]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
FD&C blue no. 1	E00263	19700	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Quinoline yellow WS	E00309	24671	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Ammonia	E00007	222	Alkalizing agent
Crospovidone	E00626	Not Available	Disintegrant
Dextrin	E00359	62698	Binding agent; Diluent; Microencapsulating agent; Stiffening agent; Suspending agent; Viscosity-controlling agent
Edetate disodium	E00186	8759	Complexing agent
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Poloxamer 188	E00645	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Poloxamer 407	E00646	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Potassium hydroxide	E00233	14797	Alkalizing agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Sodium ascorbate	E00554	23667548	Antioxidant
Sodium hydroxide	E00234	14798	Alkalizing agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Acitretin 25 mg capsule	25 mg	Oral Capsule	Oral
Acitretin 17.5 mg capsule	17.5 mg	Oral Capsule	Oral
Acitretin 10 mg capsule	10 mg	Oral Capsule	Oral
Acitretin 22.5 mg capsule	22.5 mg	Oral Capsule	Oral

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References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7598).
2	BDDCS applied to over 900 drugs
3	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells. Zhonghua Zhong Liu Za Zhi. 2006 Jan;28(1):21-4.
7	[Effects of all-trans-retinoic acid, acitretin and tazarotene on apoptosis and Bax/Bcl-2 expressions of human melanoma cells A375 and the significance]. Di Yi Jun Yi Da Xue Xue Bao. 2005 Aug;25(8):972-4, 978.
8	Effects of ATRA, acitretin and tazarotene on growth and apoptosis of Tca8113 cells. J Huazhong Univ Sci Technolog Med Sci. 2005;25(4):393-6. doi: 10.1007/BF02828205.
9	Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1. J Cell Mol Med. 2009 Sep;13(9A):2888-98. doi: 10.1111/j.1582-4934.2008.00397.x. Epub 2009 Jun 20.
10	Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
11	[Acitretin induces apoptosis and changes of relative signaling pathway in epidermoid carcinoma cell line A431]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Mar;35(2):182-8. doi: 10.3785/j.issn.1008-9292.2006.02.013.
12	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
13	Cerner Multum, Inc. "Australian Product Information.".
14	Gardner K, Cox T, Digre KB "Idiopathic intracranial hypertension associated with tetracycline use in fraternal twins: case reports and review." Neurology 45 (1995): 6-10. [PMID: 7824136]
15	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
16	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
17	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
18	Elsharkawy AM, Schwab U, McCarron B, et al. "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol 58 (2013): 331-3. [PMID: 23763943]
19	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
20	Canadian Pharmacists Association.
21	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
22	Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]
23	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
24	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
25	Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
26	Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.