Details of the Drug

General Information of Drug (ID: DMME8LH)

Drug Name
Alitretinoin
Indication
Disease Entry ICD 11 Status REF
Kaposi sarcoma 2B57 Approved [1]
Therapeutic Class
Anticancer Agents
Affected Organisms
Humans and other mammals
ATC Code
D11AH04: Alitretinoin
D11AH: Agents for dermatitis, excluding corticosteroids
D11A: OTHER DERMATOLOGICAL PREPARATIONS
D11: OTHER DERMATOLOGICAL PREPARATIONS
D: DERMATOLOGICALS
L01XF02: Alitretinoin
L01XF: Retinoids for cancer treatment
L01X: OTHER ANTINEOPLASTIC AGENTS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 300.4
Logarithm of the Partition Coefficient (xlogp) 6.3
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.3328 micromolar/kg/day [2]
Chemical Identifiers
Formula
C20H28O2
IUPAC Name
(2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid
Canonical SMILES
CC1=C(C(CCC1)(C)C)/C=C/C(=C\\C=C\\C(=C\\C(=O)O)\\C)/C
InChI
InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8-,16-14+
InChIKey
SHGAZHPCJJPHSC-ZVCIMWCZSA-N
Cross-matching ID
PubChem CID
449171
ChEBI ID
CHEMBL705
CAS Number
5300-03-8
UNII
1UA8E65KDZ
DrugBank ID
DB00523
TTD ID
D0G3PI
VARIDT ID
DR00315
INTEDE ID
DR2501
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Retinoic acid receptor beta (RARB) TTISP28 RARB_HUMAN Agonist [3]
Retinoic acid receptor gamma (RARG) TT1Q3IE RARG_HUMAN Modulator [3]
Retinoic acid receptor RXR-alpha (RXRA) TT6PEUO RXRA_HUMAN Agonist [3]
Retinoic acid receptor RXR-beta (RXRB) TTKLV96 RXRB_HUMAN Agonist [3]
Retinoic acid receptor RXR-gamma (RXRG) TTH029C RXRG_HUMAN Agonist [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) OT6EBDHM DHB1_HUMAN Gene/Protein Processing [5]
AH receptor-interacting protein (AIP) OTDJ3OSV AIP_HUMAN Gene/Protein Processing [6]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Gene/Protein Processing [6]
Annexin A1 (ANXA1) OT5OFDJC ANXA1_HUMAN Gene/Protein Processing [7]
ATP-binding cassette sub-family C member 6 (ABCC6) OTZT0LKT MRP6_HUMAN Gene/Protein Processing [8]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [9]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Gene/Protein Processing [10]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Gene/Protein Processing [11]
CD83 antigen (CD83) OT1V4WQF CD83_HUMAN Gene/Protein Processing [12]
Cellular retinoic acid-binding protein 1 (CRABP1) OTISDG5X RABP1_HUMAN Drug Response [13]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Kaposi sarcoma
ICD Disease Classification 2B57
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Retinoic acid receptor beta (RARB) DTT RARB 9.92E-02 -0.05 -0.21
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Alitretinoin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Porfimer Sodium DM7ZWNY Moderate Increased risk of photosensitivity reactions by the combination of Alitretinoin and Porfimer Sodium. Lung cancer [2C25] [14]
Methoxsalen DME8FZ9 Moderate Increased risk of photosensitivity reactions by the combination of Alitretinoin and Methoxsalen. Mycosis fungoides [2B01] [15]

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: 2645).
2 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
3 Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4.
4 Alitretinoin in dermatology-an update. Indian J Dermatol. 2015 Sep-Oct;60(5):520.
5 Organotin compounds enhance 17beta-hydroxysteroid dehydrogenase type I activity in human choriocarcinoma JAr cells: potential promotion of 17beta-estradiol biosynthesis in human placenta. Biochem Pharmacol. 2006 Apr 28;71(9):1349-57.
6 Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
7 Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics. Toxicol Lett. 2017 Nov 5;281:26-34. doi: 10.1016/j.toxlet.2017.09.001. Epub 2017 Sep 5.
8 Expression of the human ABCC6 gene is induced by retinoids through the retinoid X receptor. Biochem Biophys Res Commun. 2006 Dec 1;350(4):1082-7. doi: 10.1016/j.bbrc.2006.10.007. Epub 2006 Oct 10.
9 Investigation of the mechanisms by which EB1089 abrogates apoptosis induced by 9-cis retinoic acid in pancreatic cancer cells. Pancreas. 2006 Jan;32(1):93-100.
10 Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
11 Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro. Toxicology. 2023 Mar 15;487:153461. doi: 10.1016/j.tox.2023.153461. Epub 2023 Feb 16.
12 9-cis-Retinoic acid (9cRA), a retinoid X receptor (RXR) ligand, exerts immunosuppressive effects on dendritic cells by RXR-dependent activation: inhibition of peroxisome proliferator-activated receptor gamma blocks some of the 9cRA activities, and precludes them to mature phenotype development. J Immunol. 2007 May 15;178(10):6130-9. doi: 10.4049/jimmunol.178.10.6130.
13 Cellular retinoic acid binding protein I: expression and functional influence in renal cell carcinoma. Tumour Biol. 2005 Nov-Dec;26(6):313-23. doi: 10.1159/000089262. Epub 2005 Oct 25.
14 Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]
15 Cerner Multum, Inc. "Australian Product Information.".