Details of the Drug

General Information of Drug (ID: DMSE3I7)

• Drug Name: Gemcitabine
• Synonyms: Gemcitabine hydrochloride; DDFC; DFdC; DFdCyd; Folfugem; GEO; Gamcitabine; GemLip; Gemcel; Gemcin; Gemcitabina; Gemcitabinum; Gemtro; Gemzar; Zefei; Gemcitabine HCl; Gemcitabine stereoisomer; LY 188011; LY188011; Gemcitabina [INN-Spanish]; Gemcitabinum [INN-Latin]; Gemzar (TN); Gemzar (hydrochloride); Inno-D07001; LY-188011; Gemcitabine (USAN/INN)

Indication

Disease Entry	ICD 11	Status	REF
Anterior urethra cancer	N.A.	Approved	[1]
Biliary tract cancer	2C17	Approved	[1]
Carcinoma	2A00-2F9Z	Approved	[1]
Cervical cancer	2C77.0	Approved	[1]
Cholangiocarcinoma	2C12.10	Approved	[1]
Fallopian tube neoplasm	N.A.	Approved	[1]
Gallbladder carcinoma	N.A.	Approved	[1]
Leiomyosarcoma	2B58	Approved	[1]
Leukemia	N.A.	Approved	[1]
Lung cancer	2C25.0	Approved	[1]
MALT lymphoma	N.A.	Approved	[1]
Nodal marginal zone lymphoma	2A85.0	Approved	[1]
Non-small-cell lung cancer	2C25	Approved	[2]
Ovarian disorder	N.A.	Approved	[1]
Ovarian neoplasm	N.A.	Approved	[1]
Pancreatic adenocarcinoma	N.A.	Approved	[1]
Pancreatic ductal carcinoma	2C10.0	Approved	[1]
Pancreatic tumour	2C10	Approved	[1]
Posterior urethra cancer	N.A.	Approved	[1]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Splenic marginal zone lymphoma	N.A.	Approved	[1]
Urethral cancer	2C93	Approved	[1]
Urinary bladder neoplasm	N.A.	Approved	[1]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[4]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[4]
Colon cancer	2B90.Z	Investigative	[1]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 263.2
  Logarithm of the Partition Coefficient (xlogp); -1.5
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [5]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 32 mL/min/kg [6]
  Elimination: Within a week following administration of a single dose of 1000 mg/m2 infused over 30 minutes, about 92-98% of the dose was recovered in urine where 89% of the recovered dose was excreted as difluorodeoxyuridine (dFdU) and less than 10% as gemcitabine [7]
  Half-life: The concentration or amount of drug in body reduced by one-half in 0.7 - 1.6 hours [8]
  Metabolism: The drug is metabolized via the deoxycytidine kinase [9]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 93.9 micromolar/kg/day [10]
  Unbound Fraction: The unbound fraction of drug in plasma is 1% [6]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.5 L/kg [6]
  Water Solubility: The ability of drug to dissolve in water is measured as 15 mg/mL [5]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Fatigue	Not Available	ERBB2	OTOAUNCK	[11]
Haematotoxicity	rs11141915	DAPK1	OTNCNUCO	[12]
Neutropenia	rs9609078	OSBP2	OTDGLB4J	[13]
Neutropenia	rs2547917	PDE4D	OT1RWFV0	[13]
Neutropenia	rs12900463	ALPK3	OTLUYSMO	[13]

• Chemical Identifiers:
  Formula: C9H11F2N3O4
  IUPAC Name: 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
  Canonical SMILES: C1=CN(C(=O)N=C1N)[C@H]2C([C@@H]([C@H](O2)CO)O)(F)F
  InChI: InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
  InChIKey: SDUQYLNIPVEERB-QPPQHZFASA-N
• Cross-matching ID:
  PubChem CID: 60750
  ChEBI ID: CHEBI:175901
  CAS Number: 95058-81-4
  DrugBank ID: DB00441
  TTD ID: D03UVS
  VARIDT ID: DR00063
  INTEDE ID: DR0765
• 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
Ribonucleoside-diphosphate reductase M2 (RRM2)	TTBWDI0	RIR2_HUMAN	Modulator	[14]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Concentrative nucleoside transporter 1 (SLC28A1)	DT0EQPW	S28A1_HUMAN	Substrate	[15]
Multidrug resistance-associated protein 5 (ABCC5)	DTYVM24	MRP5_HUMAN	Substrate	[16]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[17]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytidine aminohydrolase (CDA)	DEKEDRC	CDD_HUMAN	Substrate	[18]
Cytidine deaminase (cdd)	DETX3A5	CDD_ECOLI	Substrate	[19]
Cytidine deaminase (cdd)	DEFVABT	CDD_KLEP7	Substrate	[19]
Uridine/cytidine monophosphate kinase (UMPK)	DEMPH4I	KCY_HUMAN	Substrate	[20]
Cytidine deaminase (cdd)	DEYILK4	E0TLJ6_MYCHH	Substrate	[21]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[22]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2)	OT5I4Y9K	PLCB_HUMAN	Gene/Protein Processing	[22]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Post-Translational Modifications	[23]
3',5'-cyclic-AMP phosphodiesterase 4D (PDE4D)	OT1RWFV0	PDE4D_HUMAN	Drug Response	[13]
3-phosphoinositide-dependent protein kinase 1 (PDPK1)	OTT09ZVP	PDPK1_HUMAN	Drug Response	[24]
5,6-dihydroxyindole-2-carboxylic acid oxidase	OTRK49R4	TYRP1_HUMAN	Gene/Protein Processing	[22]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Gene/Protein Processing	[25]
ADP-ribosylation factor 1 (ARF1)	OT5C4C3L	ARF1_HUMAN	Gene/Protein Processing	[22]
Aldehyde dehydrogenase 1A1 (ALDH1A1)	OTCUWZKB	AL1A1_HUMAN	Gene/Protein Processing	[26]
Alpha-2-macroglobulin (A2M)	OTFTX90K	A2MG_HUMAN	Gene/Protein Processing	[25]

Molecular Expression Atlas of This Drug

• The Studied Disease: Anterior urethra cancer

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Ribonucleoside-diphosphate reductase M2 (RRM2)	DTT	RRM2	1.66E-04	2.66	1.68
Multidrug resistance-associated protein 5 (ABCC5)	DTP	MRP5	8.28E-03	6.40E-01	7.46E-01
P-glycoprotein 1 (ABCB1)	DTP	P-GP	2.74E-01	-2.19E-01	-3.03E-01
Concentrative nucleoside transporter 1 (SLC28A1)	DTP	CNT1	2.99E-02	-3.24E-01	-1.02E+00
Uridine/cytidine monophosphate kinase (UMPK)	DME	CMPK1	2.73E-04	5.37E-01	1.41E+00
Cytidine aminohydrolase (CDA)	DME	CDA	1.62E-05	4.67E-01	8.77E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Gemcitabine

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[27]

Coadministration of a Drug Treating the Disease Different from Gemcitabine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[28]
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Gemcitabine and Roflumilast.	Asthma [CA23]	[27]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[29]
Ciprofloxacin XR	DM2NLS9	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Ciprofloxacin XR.	Bacterial infection [1A00-1C4Z]	[29]
Trovafloxacin	DM6AN32	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Trovafloxacin.	Bacterial infection [1A00-1C4Z]	[29]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[29]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[29]
Norfloxacin	DMIZ6W2	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Norfloxacin.	Bacterial infection [1A00-1C4Z]	[29]
ABT-492	DMJFD2I	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[29]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[29]
Lomefloxacin	DMVRH9C	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Lomefloxacin.	Bacterial infection [1A00-1C4Z]	[29]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Gemcitabine and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[30]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Cannabidiol.	Epileptic encephalopathy [8A62]	[27]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[31]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[32]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Gemcitabine and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[33]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Gemcitabine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[34]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Gemcitabine and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[35]
Methotrexate	DM2TEOL	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Methotrexate.	Leukaemia [2A60-2B33]	[27]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Gemcitabine and Denosumab.	Low bone mass disorder [FB83]	[36]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[37]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Idelalisib.	Mature B-cell leukaemia [2A82]	[38]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Clofarabine.	Mature B-cell lymphoma [2A85]	[39]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Gemcitabine and Thalidomide.	Multiple myeloma [2A83]	[40]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Gemcitabine and Tecfidera.	Multiple sclerosis [8A40]	[41]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Gemcitabine and Siponimod.	Multiple sclerosis [8A40]	[42]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Gemcitabine and Fingolimod.	Multiple sclerosis [8A40]	[43]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Gemcitabine and Ocrelizumab.	Multiple sclerosis [8A40]	[44]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Gemcitabine and Ozanimod.	Multiple sclerosis [8A40]	[27]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Gemcitabine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[45]
Gatifloxacin	DMSL679	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[29]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Gemcitabine and Canakinumab.	Rheumatoid arthritis [FA20]	[46]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Gemcitabine and Rilonacept.	Rheumatoid arthritis [FA20]	[46]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Gemcitabine and Golimumab.	Rheumatoid arthritis [FA20]	[47]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Gemcitabine and Leflunomide.	Rheumatoid arthritis [FA20]	[34]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Gemcitabine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[48]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Gemcitabine and Naltrexone.	Substance abuse [6C40]	[49]
Azathioprine	DMMZSXQ	Moderate	Additive immunosuppressive effects by the combination of Gemcitabine and Azathioprine.	Transplant rejection [NE84]	[42]
Cinoxacin	DM4EWNS	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Cinoxacin.	Urinary tract infection [GC08]	[29]
Nalidixic acid	DMRM0JV	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Nalidixic acid.	Urinary tract infection [GC08]	[29]
Enoxacin	DMYTE6L	Minor	Decreased absorption of Gemcitabine due to intestinal mucosa variation caused by Enoxacin.	Urinary tract infection [GC08]	[29]
Ganciclovir	DM1MBYQ	Moderate	Additive myelosuppressive effects by the combination of Gemcitabine and Ganciclovir.	Virus infection [1A24-1D9Z]	[42]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Gemcitabine and Valganciclovir.	Virus infection [1A24-1D9Z]	[42]

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