Details of the Drug

General Information of Drug (ID: DMHTYK3)

Drug Name

Ustekinumab

Synonyms

6,6-Dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine; WR99210; WR-99210; 6,6-DIMETHYL-1-[3-(2,4,5-TRICHLOROPHENOXY)PROPOXY]-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE; 47326-86-3; BRN 0629517; WR 99210; 1,3,5-Triazine-2,4-diamine, 1,6-dihydro-6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-; WR-99,210; CHEMBL129788; BRL 6231; 1,6-Dihydro-6,6-dimethyl-1-(3-(2,4,5-trichlorophenoxy)-propoxy)-1,3,5-triazine-2 ,4-diamine; 1-(2',4',5'-Trichlorophenoxypropoxy)-1,2-dihydro-2,2-dimethyl-4,6-diamino-s-triazine; Stelara (TN)

Indication

Disease Entry	ICD 11	Status	REF
Plaque psoriasis	EA90.0	Approved	[1], [2]
Psoriasis vulgaris	EA90	Phase 3	[1], [2]
Inflammatory bowel disease	DD72	Phase 2/3	[1], [2]
Malaria	1F40-1F45	Investigative	[3], [4]

Drug Type

Antibody

Sequence

>heavy chain
EVQLVQSGAEVKKPGESLKISCKGSGYSFTTYWLGWVRQMPGKGLDWIGIMSPVDSDIRY
SPSFQGQVTMSVDKSITTAYLQWNSLKASDTAMYYCARRRPGQGYFDFWGQGTLVTVSSS
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH
>light chain
DIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYNIYPYTFGQGTKLEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

ADMET Property

Bioavailability: The bioavailability of drug is 57.2% [5]
Clearance: The clearance of drug is 2.7-5.3 mL/day/kg [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 19.8 days (adminutesistration of a single subcutaneous dose of 45 mg), and 21.2 days (adminutesistration of a single subcutaneous dose of 90 mg) [5]
Metabolism: The drug is metabolized via the catabolic pathways in the same manner as endogenous IgG [6]
Vd: The volume of distribution (Vd) of drug is 4.62 L [7]

Cross-matching ID

DrugBank ID: DB05679
TTD ID: D0A2UV

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Interleukin-12 alpha (IL12A)	TTRTK6Y	IL12A_HUMAN	Not Available	[2], [8], [9]
Interleukin-23 (IL23)	TTC1GLB	IL23A_HUMAN	Not Available	[2], [8], [9]
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[3], [4]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Plaque psoriasis

ICD Disease Classification

EA90.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Interleukin-12 alpha (IL12A)	DTT	IL12A	2.40E-03	0.29	1

Molecular Expression Atlas (MEA)

MEA Detail

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 Ustekinumab (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Oliceridine	DM6MDCF	Moderate	Altered metabolism of Ustekinumab due to Oliceridine alters the formation of CYP450 enzymes.	Acute pain [MG31]	[25]
Levonorgestrel	DM1DP7T	Moderate	Altered metabolism of Ustekinumab due to Levonorgestrel alters the formation of CYP450 enzymes.	Contraceptive management [QA21]	[25]
Rivaroxaban	DMQMBZ1	Moderate	Altered metabolism of Ustekinumab due to Rivaroxaban alters the formation of CYP450 enzymes.	Deep vein thrombosis [BD71]	[25]
Oestradiol valerate and dienogest	DMZK0FQ	Moderate	Altered metabolism of Ustekinumab due to Oestradiol valerate and dienogest alters the formation of CYP450 enzymes.	Endometriosis [GA10]	[26]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Ustekinumab and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[27]
Levamlodipine	DM92S6N	Moderate	Altered metabolism of Ustekinumab due to Levamlodipine alters the formation of CYP450 enzymes.	Hypertension [BA00-BA04]	[25]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Ustekinumab and Denosumab.	Low bone mass disorder [FB83]	[28]
Lurbinectedin	DMEFRTZ	Moderate	Additive myelosuppressive effects by the combination of Ustekinumab and Lurbinectedin.	Lung cancer [2C25]	[25]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Ustekinumab and Siponimod.	Multiple sclerosis [8A40]	[29]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Ustekinumab and Fingolimod.	Multiple sclerosis [8A40]	[30]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Ustekinumab and Ocrelizumab.	Multiple sclerosis [8A40]	[31]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Ustekinumab and Ozanimod.	Multiple sclerosis [8A40]	[25]
Temsirolimus	DMS104F	Moderate	Additive immunosuppressive effects by the combination of Ustekinumab and Temsirolimus.	Renal cell carcinoma [2C90]	[25]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Ustekinumab and Canakinumab.	Rheumatoid arthritis [FA20]	[32]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Ustekinumab and Rilonacept.	Rheumatoid arthritis [FA20]	[32]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Ustekinumab and Golimumab.	Rheumatoid arthritis [FA20]	[33]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Ustekinumab when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[34]
Apixaban	DM89JLN	Moderate	Altered metabolism of Ustekinumab due to Apixaban alters the formation of CYP450 enzymes.	Thrombosis [DB61-GB90]	[25]
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⏷ Show the Full List of 18 DDI Information 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: 6885).
2	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
3	Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother. 2002 Nov;46(11):3362-9.
4	Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6.
5	STELARA? (ustekinumab) Product Monograph - Janssen Inc.
6	STELARA? (ustekinumab) injection - FDA Label
7	STELARA? (ustekinumab) injection -Janssen Full Prescribing Information
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9	Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59.
10	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
11	Interleukin-23 in the pathogenesis and treatment of psoriasis. Skin Therapy Lett. 2015 Mar-Apr;20(2):1-4.
12	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
13	Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015 Jul;136(1):116-124.e7.
14	Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9.
15	Clinical pipeline report, company report or official report of Moderna Therapeutics.
16	Preclinical development of AMG 139, a human antibody specifically targeting IL-23. Br J Pharmacol. 2015 Jan;172(1):159-72.
17	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
18	Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis. Arthritis Res Ther. 2008;10(5):R122.
19	The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
20	Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
21	Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. J Mol Biol. 2000 Jan 14;295(2):307-23.
22	Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
23	Loss of folylpoly-gamma-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int J Cancer. 2003 Feb 20;103(5):587-99.
24	How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
25	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
26	Product Information. Cosentyx (secukinumab). Novartis Pharmaceuticals, East Hanover, NJ.
27	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
28	Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
29	Cerner Multum, Inc. "Australian Product Information.".
30	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
31	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
32	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
33	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
34	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]