Details of the Drug

General Information of Drug (ID: DMX2358)

• Drug Name: Adapalene
• Synonyms: Adaferin; Adapaleno; Adapalenum; Differin; Differine; CD 271; CD271; Adaferin (TN); Adapaleno [INN-Spanish]; Adapalenum [INN-Latin]; CD-271; Differin (TN); Differin, Adapalene; KS-1196; Adapalene [USAN:BAN:INN]; Adapalene (JAN/USAN/INN); 6-(3-(1-Adamantyl)-4-methoxyphenyl)-2-naphthoic acid; 6-(3-adamantan-1-yl-4-methoxyphenyl)naphthalene-2-carboxylic acid; 6-[3-(1-adamantyl)-4-methoxyphenyl]naphthalene-2-carboxylic acid; 6-[3-(adamantan-1-yl)-4-methoxyphenyl]-2-naphthoic acid

Indication

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[1], [2]

• Therapeutic Class: Dermatologic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 412.5
  Topological Polar Surface Area (xlogp); 7.7
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.2078 micromolar/kg/day [4]
• Chemical Identifiers:
  Formula: C28H28O3
  IUPAC Name: 6-[3-(1-adamantyl)-4-methoxyphenyl]naphthalene-2-carboxylic acid
  Canonical SMILES: COC1=C(C=C(C=C1)C2=CC3=C(C=C2)C=C(C=C3)C(=O)O)C45CC6CC(C4)CC(C6)C5
  InChI: InChI=1S/C28H28O3/c1-31-26-7-6-23(21-2-3-22-12-24(27(29)30)5-4-20(22)11-21)13-25(26)28-14-17-8-18(15-28)10-19(9-17)16-28/h2-7,11-13,17-19H,8-10,14-16H2,1H3,(H,29,30)
  InChIKey: LZCDAPDGXCYOEH-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 60164
  ChEBI ID: CHEBI:31174
  CAS Number: 106685-40-9
  DrugBank ID: DB00210
  TTD ID: D0JC9N
  ACDINA ID: D00808

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Retinoic acid receptor (RAR)	TTOD7B3	NOUNIPROTAC	Binder	[5], [6]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Adapalene (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Porfimer Sodium	DM7ZWNY	Moderate	Increased risk of photosensitivity reactions by the combination of Adapalene and Porfimer Sodium.	Lung cancer [2C25]	[17]
Methoxsalen	DME8FZ9	Moderate	Increased risk of photosensitivity reactions by the combination of Adapalene and Methoxsalen.	Mycosis fungoides [2B01]	[18]
Verteporfin	DMIY6DB	Moderate	Increased risk of photosensitivity reactions by the combination of Adapalene and Verteporfin.	Psoriasis [EA90]	[19]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Acrylic acid	E00132	6581	Other agent
methylparaben	E00149	7456	Antimicrobial preservative
Edetate disodium	E00186	8759	Complexing agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Sodium hydroxide	E00234	14798	Alkalizing agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Adapalene 0.3% gel	0.30%	Gel	Topical
Adapalene 0.1% gel	0.10%	Gel	Topical

Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 5429).
• [2] Topical retinoids in acne vulgaris: update on efficacy and safety. Am J Clin Dermatol. 2008;9(6):369-81.
• [3] BDDCS applied to over 900 drugs
• [4] 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
• [5] A review of adapalene in the treatment of acne vulgaris. J Adolesc Health. 2008 Nov;43(5):421-4.
• [6] Topical treatment in acne: current status and future aspects. Dermatology. 2003;206(1):29-36.
• [7] Vitamins and cofactors: highlights of ESBOC 2009. Nat Chem Biol. 2009 Aug;5(8):530-3.
• [8] Retinoids--which dermatological indications will benefit in the near future Skin Pharmacol Appl Skin Physiol. 2001 Sep-Oct;14(5):303-15.
• [9] Retinoid agonist isotretinoin ameliorates obstructive renal injury. J Urol. 2003 Oct;170(4 Pt 1):1398-402.
• [10] National Cancer Institute Drug Dictionary (drug id 39582).
• [11] Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma. BMC Cancer. 2013 Apr 15;13:191.
• [12] 13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. J Invest Dermatol. 2000 Aug;115(2):321-7.
• [13] Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663-74.
• [14] Initial clinical trial of oral TAC-101, a novel retinoic acid receptor-alpha selective retinoid, in patients with advanced cancer. J Clin Oncol. 2002 Aug 15;20(16):3522-32.
• [15] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027956)
• [16] An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium. Br J Cancer. 2004 Aug 2;91(3):580-8.
• [17] Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]
• [18] Cerner Multum, Inc. "Australian Product Information.".
• [19] Cerner Multum, Inc. "UK Summary of Product Characteristics.".