Details of the Drug

General Information of Drug (ID: DM7UP8X)

• Drug Name: Pegfilgrastim
• Synonyms: Neulasta; Neulasta (TN); Pegfilgrastim (INN)

Indication

Disease Entry	ICD 11	Status	REF
Central nervous system neoplasm	N.A.	Approved	[1]
Hemoglobinopathy	N.A.	Approved	[2]
Lymphoma	2A80-2A86	Approved	[3]
Malignant solid tumour	2C10-2F32	Approved	[4]
MALT lymphoma	N.A.	Approved	[2]
Nodal marginal zone lymphoma	2A85.0	Approved	[2]
Non-small-cell lung cancer	2C25.Y	Approved	[5]
Plasma cell myeloma	2A83.1	Approved	[6]
Splenic marginal zone lymphoma	N.A.	Approved	[2]
Thalassemia	3A50	Approved	[7]

• Therapeutic Class: Immunomodulatory Agents
• Affected Organisms: Humans and other mammals
• ATC Code:
  L03AA13: Pegfilgrastim
  L03AA: Colony stimulating factors
  L03A: IMMUNOSTIMULANTS
  L03: IMMUNOSTIMULANTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• Sequence:
  MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA
  PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ
  QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 730.7
  Logarithm of the Partition Coefficient (xlogp); -8.6
  Rotatable Bond Count (rotbonds); 19
  Hydrogen Bond Donor Count (hbonddonor); 12
  Hydrogen Bond Acceptor Count (hbondacc); 20
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 360 mcgh/L [8]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 21 mcg/L [8]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 4-5 h [8]
  Bioavailability: The bioavailability of drug is 80% [8]
  Clearance: The clearance of drug is 14 mL/h/kg [9]
  Half-life: The concentration or amount of drug in body reduced by one-half in 15 - 80 hours [10]
  Metabolism: The drug is metabolized via the neutrophil and undergoes nonspecific degradation [11]
  Vd: The volume of distribution (Vd) of drug is 170 L []
• Chemical Identifiers:
  Formula: C27H46N4O19
  IUPAC Name: (2R,4S,5R,6R)-2-[[(2R,3R,4R,5R,6S)-5-acetamido-6-[(1S,2R)-1-amino-1-carboxypropan-2-yl]oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
  Canonical SMILES: C[C@H]([C@@H](C(=O)O)N)O[C@@H]1[C@@H]([C@H]([C@H]([C@H](O1)CO[C@@]2(C[C@@H]([C@H]([C@@H](O2)[C@@H]([C@@H](CO)O)O)NC(=O)CNC(=O)OCCOC)O)C(=O)O)O)O)NC(=O)C
  InChI: InChI=1S/C27H46N4O19/c1-10(16(28)23(40)41)48-24-18(30-11(2)33)21(39)20(38)14(49-24)9-47-27(25(42)43)6-12(34)17(22(50-27)19(37)13(35)8-32)31-15(36)7-29-26(44)46-5-4-45-3/h10,12-14,16-22,24,32,34-35,37-39H,4-9,28H2,1-3H3,(H,29,44)(H,30,33)(H,31,36)(H,40,41)(H,42,43)/t10-,12+,13-,14-,16+,17-,18-,19-,20+,21-,22-,24+,27-/m1/s1
  InChIKey: GAQMWPRWVIGRRV-IVDGIBIRSA-N
• Cross-matching ID:
  PubChem CID: 70683024
  UNII: 3A58010674
  DrugBank ID: DB00019
  TTD ID: D0AT8C
• 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
Granulocyte colony-stimulating factor receptor (G-CSF-R)	TTC70AJ	CSF3R_HUMAN	Binder	[12]

Molecular Expression Atlas of This Drug

• The Studied Disease: Central nervous system neoplasm

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Granulocyte colony-stimulating factor receptor (G-CSF-R)	DTT	CSF3R	2.08E-08	0.36	0.96

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cladribine	DM3JDRP	Major	Additive immunosuppressive effects by the combination of Pegfilgrastim and Cladribine.	Mature B-cell leukaemia [2A82]	[13]

References

• [1] Pegfilgrastim-induced hyperleukocytosis. Ann Pharmacother. 2007 Sep;41(9):1524-30.
• [2] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [3] Feasibility and efficacy of low-dose pegfilgrastim for CD34(+) cell mobilization in lymphoma. J Clin Apher. 2020 Sep;35(5):413-419.
• [4] 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: 6969).
• [5] Efficacy and safety of second-line therapy of docetaxel plus ramucirumab after first-line platinum-based chemotherapy plus immune checkpoint inhibitors in non-small cell lung cancer (SCORPION): a multicenter, open-label, single-arm, phase 2 trial. EClinicalMedicine. 2023 Nov 10;66:102303.
• [6] Effectiveness of biosimilar pegfilgrastim in patients with multiple myeloma after high-dose melphalan and autologous stem cell transplantation. Ann Hematol. 2023 Jul;102(7):1915-1925.
• [7] Evaluating the safety and effectiveness of PegaGen(?) (pegfilgrastim) for the prevention of chemotherapy-induced febrile neutropenia: a post-marketing surveillance study. Support Care Cancer. 2022 Oct;30(10):8151-8158.
• [8] The clinical pharmacokinetics of escitalopram. Clin Pharmacokinet. 2007;46(4):281-90. doi: 10.2165/00003088-200746040-00002.
• [9] Neulasta (pegfilgrastim) - FDA Label
• [10] The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Curr Pharm Des. 2004;10(11):1235-44. doi: 10.2174/1381612043452613.
• [11] pegfilgrastim | Cancer Care Ontario
• [12] Evidence that the granulocyte colony-stimulating factor (G-CSF) receptor plays a role in the pharmacokinetics of G-CSF and PegG-CSF using a G-CSF-R KO model. Pharmacol Res. 2004 Jul;50(1):55-8.
• [13] Cerner Multum, Inc. "UK Summary of Product Characteristics.".