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

General Information of Drug (ID: DM0D9YJ)

• Drug Name: Dirithromycin Drug Info
• Synonyms: Dirithromycine; Dirithromycinum; Diritromicina; Divitross; Dynabac; Noriclan; Valodin; Dirithromycine [French]; Dirithromycinum [Latin]; Diritromicina [Spanish]; LY 237216; AS-E 136; ASE-136; Dynabac (TN); LY-237216; Dirithromycin (USP/INN); Dirithromycin [USAN:BAN:INN]; (9S)-9-deoxo-11-deoxy-9,11-[imino[2-(2-methoxyethoxy)ethylidene]erythromycin

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]
Bronchitis	CA20	Approved	[2]
Mycoplasma pneumoniae pneumonia		Approved	[2]
Pars planitis		Approved	[2]
Pneumonia	CA40	Approved	[2]
Staphylococcus aureus infection		Approved	[2]

• Therapeutic Class: Antibiotics
• Cross-matching ID:
  PubChem CID: 6473883
  ChEBI ID: CHEBI:474014
  CAS Number: CAS 62013-04-1
  TTD Drug ID: DM0D9YJ
  VARIDT Drug ID: DR01366
  INTEDE Drug ID: DR0516

Molecule-Related Drug Atlas

Drug(s) Targeting Bacterial 50S ribosomal RNA (Bact 50S rRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[6]
Telithromycin	DMZ4P3A	Bacterial infection	1A00-1C4Z	Approved	[7]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[8]
Clindamycin	DM15HL8	Acne vulgaris	ED80	Approved	[8]
Zithromax	DMN4H2O	Syphilis infection	1A6Z	Approved	[9]
Troleandomycin	DMUZNIG	Bacterial infection	1A00-1C4Z	Approved	[10]
Retapamulin	DM9JXB7	Impetigo	1B72	Approved	[11]
Dalfopristin	DM4LTKV	Bacterial infection	1A00-1C4Z	Approved	[12]
Tedizolid	DMG2SKR	Skin infection	1F28-1G0Z	Approved	[13]
Gentamicine sulfate	DMBT7MI	Bacterial infection	1A00-1C4Z	Approved	[14]

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
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	[18]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[19]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[20]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[21]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]

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	[24]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[25]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[26]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[27]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[28]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[29]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[30]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[31]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[25]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial 50S ribosomal RNA (Bact 50S rRNA)	TTUWYEA	NOUNIPROTAC	Binder	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [2] Dirithromycin FDA Label
• [3] Review of macrolides and ketolides: focus on respiratory tract infections. Drugs. 2001;61(4):443-98.
• [4] Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
• [5] Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14.
• [6] A synthetic alanyl-initiator tRNA with initiator tRNA properties as determined by fluorescence measurements: comparison to a synthetic alanyl-elongator tRNA. Nucleic Acids Res. 1991 Oct 25;19(20):5749-54.
• [7] An examination of the differential sensitivity to ketolide antibiotics in ermB strains of Streptococcus pyogenes and Streptococcus pneumoniae. Curr Microbiol. 2004 Oct;49(4):239-47.
• [8] Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
• [9] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [10] Depression of colony formation by human thymus-derived lymphocytes with rifampin and other antimicrobial agents. J Infect Dis. 1981 Jun;143(6):832-5.
• [11] Retapamulin inhibition of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells. Antimicrob Agents Chemother. 2007 Sep;51(9):3385-7.
• [12] The streptogramin antibiotics: update on their mechanism of action. Expert Opin Investig Drugs. 1998 Apr;7(4):591-9.
• [13] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [14] The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo. J Mol Biol. 2002 Sep 13;322(2):273-9.
• [15] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [16] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [17] The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
• [18] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [19] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [20] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [21] The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
• [22] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [23] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [24] 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.
• [25] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [26] 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.
• [27] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [28] 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.
• [29] 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.
• [30] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [31] 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.
• [32] 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.