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

General Information of Drug (ID: DM2OZ3G)

• Drug Name: Ixabepilone Drug Info
• Synonyms: Azaepothilone B; BMS-247550; Ixempra (TN)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]
Breast carcinoma		Approved	[2]

• Cross-matching ID:
  PubChem CID: 6445540
  ChEBI ID: CHEBI:63605
  CAS Number: CAS 219989-84-1
  TTD Drug ID: DM2OZ3G
  VARIDT Drug ID: DR01285
  INTEDE Drug ID: DR0900
  ACDINA Drug ID: D01188

Molecule-Related Drug Atlas

Drug(s) Targeting Tubulin (TUB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[6]
Vinorelbine	DMVXFYE	Advanced cancer	2A00-2F9Z	Approved	[7]
Cabazitaxel	DMPAZHC	Breast cancer	2C60-2C65	Approved	[3]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[8]
Eribulin	DM1DX4Q	Breast cancer	2C60-2C65	Approved	[3]
Epothilon	DMITJRU	Ovarian cancer	2C73	Phase 3	[9]
DOLASTATIN-10	DMDUV1S	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
BMS-188797	DML1CK2	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
Indibulin	DM6OFJ8	Advanced sarcoma	2A60-2C35	Phase 2	[12]
Soblidotin	DMO4EYX	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[14]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[16]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[17]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[16]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[16]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[18]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]

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	[21]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[22]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[24]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[25]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[27]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[28]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[22]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Stablizer	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[5]

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: 6824).
• [2] Ixabepilone FDA Label
• [3] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [4] Ixabepilone, a novel microtubule-targeting agent for breast cancer, is a substrate for P-glycoprotein (P-gp/MDR1/ABCB1) but not breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2011 May;337(2):423-32.
• [5] The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: a first in class epothilone B analogue in late-phase clinical development. Clin Cancer Res. 2008 May 1;14(9):2701-9.
• [6] Docetaxel: a review of its use in metastatic breast cancer. Drugs. 2005;65(17):2513-31.
• [7] Vinca alkaloid and MDR1. Gan To Kagaku Ryoho. 2008 Jul;35(7):1086-9.
• [8] Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity. Biochemistry. 2009 Jul 28;48(29):6963-74.
• [9] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
• [10] Synthesis and biological activity of chimeric structures derived from the cytotoxic natural compounds dolastatin 10 and dolastatin 15. J Med Chem. 1998 Apr 23;41(9):1524-30.
• [11] Phase I and pharmacokinetic study of BMS-188797, a new taxane analog, administered on a weekly schedule in patients with advanced malignancies. Clin Cancer Res. 2003 Nov 1;9(14):5187-94.
• [12] 2011 Pipeline of ZioPharm.
• [13] Antitumor activity of TZT-1027 (Soblidotin). Anticancer Res. 2006 May-Jun;26(3A):1973-81.
• [14] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [15] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [16] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [17] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [18] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [19] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [20] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [21] 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.
• [22] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [23] 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.
• [24] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [25] 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.
• [26] 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.
• [27] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [28] 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.
• [29] 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.