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

General Information of Drug (ID: DMFI7A8)

• Drug Name: 6-Benzyloxy-9H-purin-2-ylamine Drug Info
• Synonyms: 6-O-Benzylguanine; 19916-73-5; 6-(Benzyloxy)-7H-purin-2-amine; 2-amino-6-benzyloxypurine; 6-(benzyloxy)-9H-purin-2-amine; 2-Amino-6-(benzyloxy)purine; O(6)-Bgua; 6-(Benzyloxy)guanine; 6-Benzyloxyguanine; 6-Benzyloxy guanine; 6-(Phenylmethoxy)-1H-purin-2-amine; 2-Amino-6-(phenylmethoxy)-9H-purine; O6-BG; UNII-01KC87F8FE; 1H-Purin-2-amine, 6-(phenylmethoxy)-; 6-BENZYLGUANINE; Purine, 2-amino-6-(benzyloxy)-; NSC 637037; CHEMBL407874; 01KC87F8FE; 6-benzyloxy-7H-purin-2-amine

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 4578
  ChEBI ID: CHEMBL407874
  CAS Number: CAS 19916-73-5
  TTD Drug ID: DMFI7A8
  INTEDE Drug ID: DR0022

Molecule-Related Drug Atlas

Drug(s) Targeting O-6-methylguanine-DNA-alkyltransferase (MGMT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
O6-Benzylguanine alkylade	DM3L2GT	Sarcoma	2A60-2C35	Phase 3	[3]
S-Methylcysteine	DMAMRKS	Discovery agent	N.A.	Investigative	[4]
6-Benzyloxy-5-nitroso-pyrimidine-2,4-diamine	DMUFSE2	Discovery agent	N.A.	Investigative	[1]
6-Benzyloxy-5-nitro-pyrimidine-2,4-diamine	DMK8XIO	Discovery agent	N.A.	Investigative	[1]
Benzylcysteine	DMTCYHM	Discovery agent	N.A.	Investigative	[4]
6-Allyloxy-9H-purin-2-ylamine	DMI2XUQ	Discovery agent	N.A.	Investigative	[5]

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	[6]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[7]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[8]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[9]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[12]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[13]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[14]

Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[15]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[12]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[21]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
O-6-methylguanine-DNA-alkyltransferase (MGMT)	TTJ8DV7	MGMT_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[2]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[2]

References

• [1] Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)-(benzyloxy)-2,6(4)-... J Med Chem. 1998 Feb 12;41(4):503-8.
• [2] Human liver oxidative metabolism of O6-benzylguanine. Biochem Pharmacol. 1995 Oct 26;50(9):1385-9.
• [3] Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma. J Clin Oncol. 2009 Mar 10;27(8):1262-7.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Resistance-modifying agents. 8. Inhibition of O(6)-alkylguanine-DNA alkyltransferase by O(6)-alkenyl-, O(6)-cycloalkenyl-, and O(6)-(2-oxoalkyl)gua... J Med Chem. 2000 Nov 2;43(22):4071-83.
• [6] 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.
• [7] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [8] 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.
• [9] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [10] 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.
• [11] 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.
• [12] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [13] 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.
• [14] 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.
• [15] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [16] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [17] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [18] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [19] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [20] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [21] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [22] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [23] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.