Details of the Drug

General Information of Drug (ID: DMAO80I)

• Drug Name: Pralatrexate
• Synonyms: Folotyn (TN)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1], [2], [3]
Peripheral T-cell lymphoma	2A90.C	Approved	[1], [2], [3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 477.5
  Topological Polar Surface Area (xlogp); -0.9
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 5
  Hydrogen Bond Acceptor Count (hbondacc); 11
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 2.7 mL/min/kg [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 12 - 18 hours [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.33% [4]
  Vd: The volume of distribution (Vd) of drug is 105 L [5]
• Chemical Identifiers:
  Formula: C23H23N7O5
  IUPAC Name: (2S)-2-[[4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl]amino]pentanedioic acid
  Canonical SMILES: C#CCC(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
  InChI: InChI=1S/C23H23N7O5/c1-2-3-14(10-15-11-26-20-18(27-15)19(24)29-23(25)30-20)12-4-6-13(7-5-12)21(33)28-16(22(34)35)8-9-17(31)32/h1,4-7,11,14,16H,3,8-10H2,(H,28,33)(H,31,32)(H,34,35)(H4,24,25,26,29,30)/t14?,16-/m0/s1
  InChIKey: OGSBUKJUDHAQEA-WMCAAGNKSA-N
• Cross-matching ID:
  PubChem CID: 148121
  ChEBI ID: CHEBI:71223
  CAS Number: 146464-95-1
  DrugBank ID: DB06813
  TTD ID: D02LWU
  VARIDT ID: DR00041
  INTEDE ID: DR1320
  ACDINA ID: D01353

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Folate transporter 1 (SLC19A1)	DTOSN46	S19A1_HUMAN	Substrate	[6]
Proton-coupled folate transporter (SLC46A1)	DTDJEMI	PCFT_HUMAN	Substrate	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Folylpolyglutamate synthase (FPGS) Main DME	DECWT2V	FOLC_HUMAN	Substrate	[7]

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
Polypeptide deformylase (PDF)	DTT	PDF	8.87E-16	-0.54	-0.86
Folate transporter 1 (SLC19A1)	DTP	FLOT1	3.94E-04	-1.44E-01	-3.83E-01
Proton-coupled folate transporter (SLC46A1)	DTP	PCFT	2.13E-02	-3.56E-02	-2.38E-01
Folylpolyglutamate synthase (FPGS)	DME	FPGS	4.94E-49	5.45E-01	1.87E+00

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Pralatrexate and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[22]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Pralatrexate and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[23]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Pralatrexate and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[24]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Pralatrexate and Cannabidiol.	Epileptic encephalopathy [8A62]	[25]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Pralatrexate and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[26]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Pralatrexate and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[27]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Pralatrexate and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[28]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Pralatrexate and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[29]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Pralatrexate and Idelalisib.	Mature B-cell leukaemia [2A82]	[30]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Pralatrexate and Tecfidera.	Multiple sclerosis [8A40]	[31]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Pralatrexate and Siponimod.	Multiple sclerosis [8A40]	[22]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Pralatrexate and Fingolimod.	Multiple sclerosis [8A40]	[32]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Pralatrexate and Ocrelizumab.	Multiple sclerosis [8A40]	[33]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Pralatrexate and Ozanimod.	Multiple sclerosis [8A40]	[25]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Pralatrexate when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[34]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Hydrochloric acid	E00015	313	Acidulant
Sodium chloride	E00077	5234	Diluent; Tonicity agent
Sodium hydroxide	E00234	14798	Alkalizing agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Pralatrexate 20mg/ml solution	20mg/ml	Solution	Intravenous
Pralatrexate 40mg/2ml solution	40mg/2ml	Solution	Intravenous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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• [26] Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
• [27] Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [28] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
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