Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM32B5U)

• Drug Name: Upadacitinib Drug Info
• Synonyms: ABT-494

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Approved	[1]
Psoriatic arthritis	FA21	Phase 3	[2]
Atopic dermatitis	EA80	Phase 2	[2]
Crohn disease	DD70	Phase 2	[3]
Ulcerative colitis	DD71	Phase 2	[3]

• Cross-matching ID:
  PubChem CID: 58557659
  CAS Number: CAS 1310726-60-3
  TTD Drug ID: DM32B5U
  ACDINA Drug ID: D01513

Molecule-Related Drug Atlas

Drug(s) Targeting Janus kinase 1 (JAK-1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Baricitinib	DM4ONW5	Rheumatoid arthritis	FA20	Approved	[5]
Ruxolitinib	DM7Q98D	Essential thrombocythemia	3B63.1Z	Approved	[6]
ASP-015K	DMZ1UOI	Psoriasis vulgaris	EA90	Phase 3	[7]
SHR0302	DMUL8ZT	Ulcerative colitis	DD71	Phase 3	[8]
Cerdulatinib	DMSCR2H	B-cell lymphoma	2A86	Phase 2	[2]
CTP-543	DM3SYOK	Alopecia	ED70	Phase 2	[3]
INCB039110	DMD9RV3	Malignant neoplasm	2A00-2F9Z	Phase 2	[7]
PF-06700841	DMMGSFV	Asthma	CA23	Phase 2	[2]
ATI-501	DMTY6OF	Alopecia	ED70	Phase 2	[9]
ATI-502	DM8NODR	Alopecia	ED70	Phase 2	[10]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[19]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[20]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[21]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[23]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[24]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[25]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[26]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[27]

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	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Population pharmacokinetics of upadacitinib using the immediate-release and extended-release formulations in healthy subjects and subjects with rheumatoid arthritis: analyses of phase I-III clinical trials. Clin Pharmacokinet. 2019 Aug;58(8):1045-1058.
• [5] Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.
• [6] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [7] 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).
• [8] Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial. Am J Clin Dermatol. 2021 Nov;22(6):877-889.
• [9] Clinical pipeline report, company report or official report of Aclaris Therapeutics.
• [10] 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.
• [11] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [12] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [13] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [14] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [15] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [16] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [17] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [18] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [19] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [20] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [21] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [22] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [23] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [24] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [25] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [26] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [27] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.