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

General Information of Drug (ID: DMSQ8MD)

• Drug Name: Anagrelide Drug Info
• Synonyms: Anagrelida; Anagrelidum; BL 416201; Agrylin (TN); Anagrelida [INN-Spanish]; Anagrelide [BAN:INN]; Anagrelide [INN:BAN]; Anagrelidum [INN-Latin]; Xagrid (TN); Anagrelide (INN/BAN); 6,7-Dichlor-1,5-dihydroimidazo(2,1-b)chinazolin-2(3H)-on; 6,7-Dichloro-1,5-dihydroimidazo(2,1-b)quinazolin-2(3H)-one; 6,7-dichloro-1,5-dihydroimidazo[2,1-]quinazolin-2(3H)-one; 6,7-dichloro-5,10-dihydro-3H-imidazo[2,1-b]quinazolin-2-one

Indication

Disease Entry	ICD 11	Status	REF
Thrombocythemia	3B63	Approved	[1]
Essential thrombocythemia	3B63.1Z	Phase 2	[2]

• Therapeutic Class: Antithrombotic Agents
• Cross-matching ID:
  PubChem CID: 135409400
  ChEBI ID: CHEMBL760
  CAS Number: CAS 68475-42-3
  TTD Drug ID: DMSQ8MD
  INTEDE Drug ID: DR0112
  ACDINA Drug ID: D00038

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 3A (PDE3A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cilostazol	DMZMSCT	Intermittent claudication	BD40.00	Approved	[5]
Aminophylline	DML2NIB	Bronchial asthma	CA23	Approved	[6]
Enoximone	DMQVZJD	Congestive heart failure	BD10	Approved	[7]
VESNARINONE	DMBKX3C	Cardiac failure	BD10-BD13	Approved	[8]
BEMORADAN	DMUL6GY	Heart failure	BD10-BD13	Phase 2	[9]
CI-930	DMADPQX	N. A.	N. A.	Discontinued in Phase 2	[10]
EMD-53998	DMVS8IE	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 1	[9]
IMAZODAN	DMWTFO3	N. A.	N. A.	Terminated	[11]
LAS-31180	DMW2K1L	Heart failure	BD10-BD13	Terminated	[12]
BMY-20844	DMDPJ8M	N. A.	N. A.	Terminated	[13]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[14]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
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
Phosphodiesterase 3A (PDE3A)	TT06AWU	PDE3A_HUMAN	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[4]

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: 7114).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45.
• [4] Open-label, dose-titration and continuation study to assess efficacy, safety, and pharmacokinetics of anagrelide in treatment-nae Japanese patients with essential thrombocythemia. Int J Hematol. 2013 Mar;97(3):360-8.
• [5] A new generation of phosphodiesterase inhibitors: multiple molecular forms of phosphodiesterase and the potential for drug selectivity. J Med Chem. 1985 May;28(5):537-45.
• [6] Topical fat reduction from the waist. Diabetes Obes Metab. 2007 May;9(3):300-3.
• [7] Inhibitors of cyclic AMP phosphodiesterase. 2. Structural variations of N-cyclohexyl-N-methyl-4-[(1,2,3,5-tetrahydro- 2-oxoimidazo[2,1-b]quinazolin... J Med Chem. 1987 Feb;30(2):303-18.
• [8] Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors. Bioorg Med Chem. 2010 Jan 15;18(2):855-62.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [10] Cardiotonic agents. 9. Synthesis and biological evaluation of a series of (E)-4,5-dihydro-6-[2-[4-(1H-imidazol-1-yl)phenyl]ethenyl]-3 (2H)-pyridazi... J Med Chem. 1989 Feb;32(2):342-50.
• [11] 3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase. J Med Chem. 1992 Feb 21;35(4):620-8.
• [12] Pharmacological profile of LAS 31180, a new inotropic/vasodilator quinolone derivative. Arzneimittelforschung. 2000 Nov;50(11):980-6.
• [13] Inhibitors of blood platelet cAMP phosphodiesterase. 3. 1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives with enhanced aqueous solubility. J Med Chem. 1992 Jul 10;35(14):2688-96.
• [14] 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.
• [15] 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.
• [16] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [17] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [18] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [19] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [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.