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
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
CHEBI:50648
CAS Number
5300-03-8
DrugBank ID
DB00523
TTD ID
D0G3PI
VARIDT ID
DR00315
INTEDE ID
DR2501
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
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1) OTO7FJA9 DHI1_HUMAN Gene/Protein Processing [5]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) OT6EBDHM DHB1_HUMAN Gene/Protein Processing [6]
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38) OTG0TTX7 CD38_HUMAN Gene/Protein Processing [7]
AH receptor-interacting protein (AIP) OTDJ3OSV AIP_HUMAN Gene/Protein Processing [5]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Gene/Protein Processing [5]
Annexin A1 (ANXA1) OT5OFDJC ANXA1_HUMAN Gene/Protein Processing [8]
Annexin A2 (ANXA2) OTFNS0CC ANXA2_HUMAN Gene/Protein Processing [8]
Annexin A5 (ANXA5) OTZS877V ANXA5_HUMAN Gene/Protein Processing [8]
Apolipoprotein A-II (APOA2) OTQ3HGTC APOA2_HUMAN Gene/Protein Processing [9]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [10]
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] [11]
Methoxsalen DME8FZ9 Moderate Increased risk of photosensitivity reactions by the combination of Alitretinoin and Methoxsalen. Mycosis fungoides [2B01] [12]

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 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.
6 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.
7 Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells. Mol Cell Biol. 2005 Jul;25(13):5648-63.
8 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.
9 Retinoids increase human apolipoprotein A-11 expression through activation of the retinoid X receptor but not the retinoic acid receptor. Mol Cell Biol. 1996 Jul;16(7):3350-60. doi: 10.1128/MCB.16.7.3350.
10 Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-gamma and altered expression of Bcl-2/Bax. Br J Cancer. 2002 Aug 27;87(5):555-61. doi: 10.1038/sj.bjc.6600496.
11 Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]
12 Cerner Multum, Inc. "Australian Product Information.".