Details of the Drug

General Information of Drug (ID: DMZ1UOI)

• Drug Name: Asp-015K
• Synonyms: Peficitinib; ASP015K; UNII-HPH1166CKX; 944118-01-8; ASP-015K; HPH1166CKX; 4-[[(1R,3S)-5-hydroxy-2-adamantyl]amino]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide; 4-[[(1S,3R)-5-oxidanyl-2-adamantyl]amino]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide; Peficitinib [USAN:INN]; ASP 015K; JNJ-54781532; 9T6; Peficitinib (USAN/INN); SCHEMBL1154421; SCHEMBL9990248; SCHEMBL4447032; GTPL8315; SCHEMBL9990240; SCHEMBL1154418; CHEMBL3137308; SCHEMBL17645135; BCP18465; BDBM50124208; SB16834; DB11708; SC-17960; ASP015K; JNJ-54781532; D10653; Peficitinib pound A

Indication

Disease Entry	ICD 11	Status	REF
Psoriasis vulgaris	EA90	Phase 3	[1], [2]
Rheumatoid arthritis	FA20	Phase 2	[3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 326.4
  Topological Polar Surface Area (xlogp); 1.9
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C18H22N4O2
  IUPAC Name: 4-[[(1S,3R)-5-hydroxy-2-adamantyl]amino]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide
  Canonical SMILES: C1[C@@H]2CC3(C[C@@H](C2NC4=C5C=CNC5=NC=C4C(=O)N)CC1C3)O
  InChI: InChI=1S/C18H22N4O2/c19-16(23)13-8-21-17-12(1-2-20-17)15(13)22-14-10-3-9-4-11(14)7-18(24,5-9)6-10/h1-2,8-11,14,24H,3-7H2,(H2,19,23)(H2,20,21,22)/t9?,10-,11+,14?,18?
  InChIKey: DREIJXJRTLTGJC-JQCLMNFQSA-N
• Cross-matching ID:
  PubChem CID: 57928403
  CAS Number: 944118-01-8
  DrugBank ID: DB11708
  TTD ID: D06EIC
  INTEDE ID: DR1774

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Inhibitor	[4]
Janus kinase 3 (JAK-3)	TTT7PJU	JAK3_HUMAN	Inhibitor	[5]
Tyrosine-protein kinase (PTK)	TTJSQEF	NOUNIPROTAC	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Sulfotransferase 2A1 (SULT2A1)	DE0P6LK	ST2A1_HUMAN	Substrate	[6]
Nicotinamide N-methyltransferase (NNMT)	DECVGJ3	NNMT_HUMAN	Substrate	[6]

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
Janus kinase 3 (JAK-3)	DTT	JAK3	4.94E-03	0.28	1.41
Nicotinamide N-methyltransferase (NNMT)	DME	NNMT	2.73E-02	-1.27E-01	-4.45E-01
Nicotinamide N-methyltransferase (NNMT)	DME	NNMT	1.75E-03	-4.71E-01	-1.97E+00
Sulfotransferase 2A1 (SULT2A1)	DME	SULT2A1	5.88E-01	3.51E-02	3.36E-01
Sulfotransferase 2A1 (SULT2A1)	DME	SULT2A1	2.71E-04	-2.83E-01	-2.39E+00

References

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• [2] ClinicalTrials.gov (NCT02308163) A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDs. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 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. (Target id: 2047).
• [5] 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. (Target id: 2049).
• [6] Human mass balance, metabolite profile and identification of metabolic enzymes of [14C]ASP015K, a novel oral janus kinase inhibitor. Xenobiotica. 2015;45(10):887-902.
• [7] Sulfation of environmental estrogens by cytosolic human sulfotransferases. Drug Metab Pharmacokinet. 2002;17(3):221-8.
• [8] Abiraterone for the treatment of metastatic castrate-resistant prostate cancer. Ann Pharmacother. 2012 Jul-Aug;46(7-8):1016-24.
• [9] Expression and characterization of the human 3 beta-hydroxysteroid sulfotransferases (SULT2B1a and SULT2B1b). J Steroid Biochem Mol Biol. 2001 Jun;77(4-5):261-9.
• [10] In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium-competitive acid blocker. Xenobiotica. 2017 Dec;47(12):1027-1034.
• [11] Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects. Birth Defects Res A Clin Mol Teratol. 2008 Mar;82(3):155-65.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.
• [15] Clinical pipeline report, company report or official report of Aclaris Therapeutics.
• [16] ClinicalTrials.gov (NCT03759340) ATI-502 Topical Solution for the Treatment of Alopecia Areata (AA), Alopecia Universalis (AU) and Alopecia Totalis (AT). U.S. National Institutes of Health.
• [17] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
• [18] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [21] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [22] Clinical pipeline report, company report or official report of Concert Pharmaceuticals.