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

General Information of Drug (ID: DMJ2O7B)

• Drug Name: Gemtuzumab ozogamicin Drug Info
• Synonyms: Mylotarg (TN)

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  TTD Drug ID: DMJ2O7B
  VARIDT Drug ID: DR00402
  INTEDE Drug ID: DR0767

Molecule-Related Drug Atlas

Drug(s) Targeting Myeloid cell surface antigen CD33 (CD33)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vadastuximab talirine	DM9LH10	Acute myeloid leukaemia	2A60	Phase 3	[4]
Actimab-A	DMKBIPR	Acute myeloid leukaemia	2A60	Phase 2	[4]
BI-836858	DMUVMY9	Myelodysplastic syndrome	2A37	Phase 2	[5]
Actimab-MDS	DMP8EEX	Myelodysplastic syndrome	2A37	Phase 2	[6]
GTB-3550	DMK2RIB	Acute myelogenous leukaemia	2A41	Phase 1/2	[7]
SGN-CD33A	DMRC7PI	Acute myeloid leukaemia	2A60	Phase 1/2	[8]
CART33 cells	DM81JIT	Myeloid leukaemia	2B33.1	Phase 1/2	[9]
CD33-specific gene-engineered T cells	DMM35D2	Acute myeloid leukaemia	2A60	Phase 1/2	[10]
Anti-CD33 CAR-T cells	DM9NPF6	Myeloid leukaemia	2B33.1	Phase 1/2	[11]
HuM-195-Ac-225	DMIU1HY	Acute myelogenous leukaemia	2A41	Phase 1/2	[12]

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	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[14]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Myeloid cell surface antigen CD33 (CD33)	TTJVYO3	CD33_HUMAN	Not Available	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]

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: 6775).
• [2] Targeted treatment of acute myeloid leukemia in older adults: role of gemtuzumab ozogamicin. Clin Interv Aging. 2009;4:197-205.
• [3] Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998 Feb;34(2):155-62.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] The past and future of CD33 as therapeutic target in acute myeloid leukemia. Blood Rev. 2014 Jul;28(4):143-53.
• [6] Clinical pipeline report, company report or official report of Actinium Pharmaceuticals
• [7] Clinical pipeline report, company report or official report of GT Biopharma.
• [8] SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood. 2013 Aug 22;122(8):1455-63.
• [9] ClinicalTrials.gov (NCT01864902) Treatment of Relapsed and/or Chemotherapy Refractory CD33 Positive Acute Myeloid Leukemia by CART-33
• [10] ClinicalTrials.gov (NCT03222674) Multi-CAR T Cell Therapy for Acute Myeloid Leukemia
• [11] ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
• [12] J Clin Oncol 29: 2011 (suppl; abstr 6516).
• [13] 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.
• [14] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [15] 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.
• [16] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [17] 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.
• [18] 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.
• [19] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [20] 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.
• [21] 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.