Natural Product (NP) Details

General Information of the NP (ID: NP9888)
Name
Acitretin
Synonyms
Acitretin; 55079-83-9; Etretin; Soriatane; Neotigason; all-trans-Acitretin; Acitretine; Retinoid etretin; (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid; Acitretina; Acitretinum; TMMP; Ro 10-1670; 13-cis-Acitretin; Ro 10-1670/000; UNII-LCH760E9T7; (all-E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid; all-trans-3,7-Dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonatetraenoic acid; CHEBI:50173; 2,4,6,8-Nonatetraenoic acid, 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-, (all-E)-; Ro-101670000; LCH760E9T7; 54757-46-9; NCGC00163127-02; Acitretine [French]; Acitretinum [Latin]; Acitretina [Spanish]; 2,4,6,8-Nonatetraenoic acid, 3,7-dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-, (all-E)-; Soriatane CK; Soriatane (TN); CCRIS 5534; Ro-10-1670; HSDB 7187; EINECS 259-474-4; CHEBI:50172; Acitretin/; U0279; all-trans-Etretin; Acitretin [USAN:USP:INN:BAN]; Acitretin,(S); 69427-46-9; Acitretin (USP/INN); Spectrum5_002065; DSSTox_CID_2553; Ro-10-1670/000; SCHEMBL3759; CHEMBL1131; DSSTox_RID_76624; DSSTox_GSID_22553; MLS001076667; BIDD:GT0617; GTPL7598; DTXSID6022553; BCPP000437; HMS2234L17; HMS3259J12; HMS3714E17; 2-Ethynyl-5-Methylpyridine1-oxide; Acitretin, >=98.0% (HPLC); HY-B0107; ZINC3798734; Tox21_112012; ABP000589; BDBM50088429; MFCD00866632; s1368; STL565770; AKOS015889991; AB07538; AC-4702; BCP9000229; CCG-220668; CS-1855; DB00459; KS-5246; NC00723; 2,4,6,8-Nonatetraenoic acid, 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-; NCGC00163127-01; NCGC00163127-03; (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-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid; (2E,4E,6E,8E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid; AS-12644; SMR000499573; AB0007949; CAS-55079-83-9; SW199134-2; D02754; AB00698376-08; AB00698376_09; Acitretin 100 microg/mL in Acetonitrile:Acetone; 079A839; A830475; Q341500; SR-01000763200; SR-01000763200-3; BRD-K90699611-001-01-4; Acitretin, British Pharmacopoeia (BP) Reference Standard; Acitretin, European Pharmacopoeia (EP) Reference Standard; Acitretin, United States Pharmacopeia (USP) Reference Standard; Acitretin, Pharmaceutical Secondary Standard; Certified Reference Material; 2,4,6,8-Nonatetraenoic acid, 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-, (2E,4E,6E,8E)-
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Species Origin Homo sapiens ...     Click to Show/Hide
Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Disease Plaque psoriasis [ICD-11: EA90] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.823
 
MDCK Permeability
 -4.72
 
PAMPA
 ++
 
HIA
 - - -
 
Distribution
VDss
 -0.337
 
PPB
 98%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 +
CYP1A2 substrate
 +++
CYP2C19 inhibitor
 -
CYP2C19 substrate
 +
CYP2C9 inhibitor
 -
CYP2C9 substrate
 - -
CYP2D6 inhibitor
 - -
CYP2D6 substrate
 - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 +
CYP2B6 inhibitor
 ++
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 - - -
 
Excretion
CLplasma
 3.28
 
T1/2
 1.093
Toxicity
DILI
 ++
 
Rat Oral Acute Toxicity
 -
 
FDAMDD
 +
 
Respiratory
 ++
 
Human Hepatotoxicity
 ++
 
Ototoxicity
 +
 
Drug-induced Nephrotoxicity
 ++
 
Drug-induced Neurotoxicity
 -
 
Hematotoxicity
 +
 
Genotoxicity
 -
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C21H26O3
PubChem CID
5284513
Canonical SMILES
CC1=CC(=C(C(=C1C=CC(=CC=CC(=CC(=O)O)C)C)C)C)OC
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
CAS Number
CAS 55079-83-9
ChEBI ID
CHEBI:50173
TTD Drug ID
D05QDC
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Methotrexate      Leukaemia     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Male K14-VEGF mice (10 weeks old) were used in this study.
                    Experimental
                    Result(s)		 The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis.
          Hydroxyurea      Myeloproliferative neoplasm     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 Hydroxyurea and acitretin as a novel combination therapy in severe plaque psoriasis.
Target and Pathway
Target(s) STAT factor 3 (STAT3)  Molecule Info  [4]
KEGG Pathway Chemokine signaling pathway Click to Show/Hide
2 HIF-1 signaling pathway
3 FoxO signaling pathway
4 Signaling pathways regulating pluripotency of stem cells
5 Jak-STAT signaling pathway
6 Prolactin signaling pathway
7 Adipocytokine signaling pathway
8 Toxoplasmosis
9 Hepatitis C
10 Hepatitis B
11 Measles
12 Epstein-Barr virus infection
13 Pathways in cancer
14 Viral carcinogenesis
15 Proteoglycans in cancer
16 MicroRNAs in cancer
17 Pancreatic cancer
18 Acute myeloid leukemia
19 Inflammatory bowel disease (IBD)
Panther Pathway Angiogenesis Click to Show/Hide
2 EGF receptor signaling pathway
3 Inflammation mediated by chemokine and cytokine signaling pathway
4 Interleukin signaling pathway
5 JAK/STAT signaling pathway
6 PDGF signaling pathway
7 Ras Pathway
8 CCKR signaling map ST
Pathway Interaction Database GMCSF-mediated signaling events Click to Show/Hide
2 IL27-mediated signaling events
3 Signaling events mediated by PTP1B
4 IL12-mediated signaling events
5 Signaling events mediated by TCPTP
6 Signaling events mediated by HDAC Class I
7 IL2-mediated signaling events
8 CXCR4-mediated signaling events
9 EGF receptor (ErbB1) signaling pathway
10 IFN-gamma pathway
11 ErbB1 downstream signaling
12 ErbB2/ErbB3 signaling events
13 IL6-mediated signaling events
14 PDGFR-beta signaling pathway
15 Neurotrophic factor-mediated Trk receptor signaling
16 IL23-mediated signaling events
17 Signaling events mediated by Stem cell factor receptor (c-Kit)
18 FGF signaling pathway
19 RAC1 signaling pathway
20 Notch-mediated HES/HEY network
21 IL12 signaling mediated by STAT4
Reactome Interleukin-6 signaling Click to Show/Hide
2 Senescence-Associated Secretory Phenotype (SASP)
3 POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
4 Transcriptional regulation of pluripotent stem cells
5 Growth hormone receptor signaling
WikiPathways Serotonin Receptor 2 and STAT3 Signaling Click to Show/Hide
2 Notch Signaling Pathway
3 Interferon type I signaling pathways
4 EPO Receptor Signaling
5 TGF Beta Signaling Pathway
6 IL-2 Signaling Pathway
7 EGF/EGFR Signaling Pathway
8 IL-4 Signaling Pathway
9 IL-6 signaling pathway
10 Signaling of Hepatocyte Growth Factor Receptor
11 Kit receptor signaling pathway
12 Nuclear Receptors Meta-Pathway
13 Estrogen Receptor Pathway
14 TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
15 IL-3 Signaling Pathway
16 Dopaminergic Neurogenesis
17 Transcriptional regulation of pluripotent stem cells
18 Mammary gland development pathway - Involution (Stage 4 of 4)
19 Signaling by SCF-KIT
20 Interleukin-6 signaling
21 Growth hormone receptor signaling
22 JAK/STAT
23 PDGF Pathway
24 BDNF signaling pathway
25 Oncostatin M Signaling Pathway
26 Adipogenesis
27 Interleukin-11 Signaling Pathway
28 AGE/RAGE pathway
29 Prostate Cancer
30 TSLP Signaling Pathway
31 IL-9 Signaling Pathway
32 IL17 signaling pathway
33 IL-7 Signaling Pathway
34 Regulation of Microtubule Cytoskeleton
35 Leptin signaling pathway
36 TSH signaling pathway
37 Cell Differentiation - Index
38 Cell Differentiation - meta
39 Signaling by PDGF
40 NGF signalling via TRKA from the plasma membrane
41 TFs Regulate miRNAs related to cardiac hypertrophy
42 MicroRNAs in cardiomyocyte hypertrophy
43 Physiological and Pathological Hypertrophy of the Heart
44 Androgen receptor signaling pathway
45 IL-5 Signaling Pathway
References
Reference 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).
Reference 2 The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis. Pharmacol Res. 2017 Jul;121:158-168.
Reference 3 Hydroxyurea and acitretin as a novel combination therapy in severe plaque psoriasis. Br J Dermatol. 2018 Nov;179(5):1212-1213.
Reference 4 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.
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