Details of the Drug

General Information of Drug (ID: DMX9ZM4)

• Drug Name: PEG-SN38
• Synonyms: EZN-2208

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[1]
Metastatic colorectal cancer	2B91	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 4:
  Molecular Weight (mw); 2300.3
  Logarithm of the Partition Coefficient (xlogp); 3.6
  Rotatable Bond Count (rotbonds); 54
  Hydrogen Bond Donor Count (hbonddonor); 8
  Hydrogen Bond Acceptor Count (hbondacc); 41
• Chemical Identifiers:
  Formula: C118H122N12O37
  IUPAC Name: [(19S)-10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl] 2-[[2-[2-[3-[2,3-bis[2-[2-[[2-[[(19S)-10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl]oxy]-2-oxoethyl]amino]-2-oxoethoxy]ethoxy]propoxy]-2-[2-[2-[[2-[[(19S)-10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl]oxy]-2-oxoethyl]amino]-2-oxoethoxy]ethoxy]propoxy]ethoxy]acetyl]amino]acetate
  Canonical SMILES: CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)[C@@]4(CC)OC(=O)CNC(=O)COCCOCC(COCC(COCCOCC(=O)NCC(=O)O[C@]5(C6=C(COC5=O)C(=O)N7CC8=C(C9=C(C=CC(=C9)O)N=C8C7=C6)CC)CC)OCCOCC(=O)NCC(=O)O[C@]3(C4=C(COC3=O)C(=O)N3CC5=C(C6=C(C=CC(=C6)O)N=C5C3=C4)CC)CC)OCCOCC(=O)NCC(=O)O[C@]3(C4=C(COC3=O)C(=O)N3CC5=C(C6=C(C=CC(=C6)O)N=C5C3=C4)CC)CC)C2=NC2=C1C=C(C=C2)O
  InChI: InChI=1S/C118H122N12O37/c1-9-67-71-33-61(131)17-21-87(71)123-103-75(67)45-127-91(103)37-83-79(107(127)143)53-160-111(147)115(83,13-5)164-99(139)41-119-95(135)57-153-27-25-151-49-65(158-31-29-155-59-97(137)121-43-101(141)166-117(15-7)85-39-93-105-77(47-129(93)109(145)81(85)55-162-113(117)149)69(11-3)73-35-63(133)19-23-89(73)125-105)51-157-52-66(159-32-30-156-60-98(138)122-44-102(142)167-118(16-8)86-40-94-106-78(48-130(94)110(146)82(86)56-163-114(118)150)70(12-4)74-36-64(134)20-24-90(74)126-106)50-152-26-28-154-58-96(136)120-42-100(140)165-116(14-6)84-38-92-104-76(46-128(92)108(144)80(84)54-161-112(116)148)68(10-2)72-34-62(132)18-22-88(72)124-104/h17-24,33-40,65-66,131-134H,9-16,25-32,41-60H2,1-8H3,(H,119,135)(H,120,136)(H,121,137)(H,122,138)/t65?,66?,115-,116-,117-,118-/m0/s1
  InChIKey: CXWRXYDTWCBSJF-DPTNTHPESA-N
• Cross-matching ID:
  PubChem CID: 59443782
  CAS Number: 946062-05-1
  TTD ID: D05UFP
  INTEDE ID: DR1826
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase I (TOP1)	TTGTQHC	TOP1_HUMAN	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

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

Molecular Expression Atlas of This Drug

• The Studied Disease: Breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
DNA topoisomerase I (TOP1)	DTT	TOP1	6.65E-01	0.2	0.39
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	5.59E-39	-3.76E-01	-1.64E+00

References

• [1] ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
• [2] EZN-2208 (PEG-SN38) overcomes ABCG2-mediated topotecan resistance in BRCA1-deficient mouse mammary tumors. PLoS One. 2012;7(9):e45248.
• [3] Phase I dose-escalation study of EZN-2208 (PEG-SN38), a novel conjugate of poly(ethylene) glycol and SN38, administered weekly in patients with advanced cancer. Cancer Chemother Pharmacol. 2013 Jun;71(6):1499-506.