Drug Details

General Information of the Drug (ID: DR8475)
Name
Pemetrexed
Synonyms
Pemetrexed; 137281-23-3; Pemetrexed disodium; Alimta; LY231514; UNII-04Q9AIZ7NO; Pemetrexed acid; CHEBI:63616; 04Q9AIZ7NO; LY-231514; (S)-2-(4-(2-(2-Amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioic acid; N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid; C20H21N5O6; 137281-23-3 (free acid); LY 231514; NSC-698037; LY-2315; N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid; Alimta (TN); (S)-2-(4-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioic acid; 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC ACID; N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid; (4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzoyl)-L-glutamic acid; (S)-2-(4-(2-(2-Amino-4-oxo-4,7-dihydro-1H-pyrrolo-[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioic acid; LYA; N-[4-[2(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid; Pemetrexed [INN:BAN]; HSDB 7316; 1juj; Pemetrexed (TN); N-(4-[2-(2-amino-4,7-Dihydro-4-Oxo-1H-Pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl)-L-Glutamic Acid; Pemetrexed (INN); Alimta (TN) (Lilly); SCHEMBL7968; US9422297, Pemetrexed; N-(4-(2-(2-Amino-3,4-dihydro-4-oxo-7H-pyrrolo(2,3-d)pyrimdin-5-yl)ethyl)benzoyl)glutamic acid; CHEMBL225072; DTXSID2048329; Premetrexed [Common mis-spelling]; ZINC1540998; BDBM50027656; CP0119; NSC698037; s5971; AKOS015896253; AKOS016842348; AC-1701; CS-1297; DB00642; NCGC00166414-11; NCGC00167517-01; NCGC00242485-01; AS-30680; HY-10820; L-Glutamic acid, N-(4-(2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo(2,3-d)pyrimidin-5-yl)ethyl)benzoyl)-; DB-024764; P2288; A12668; D07472; S-4927; 41413-EP2270012A1; 41413-EP2270013A1; 41413-EP2305681A1; 41413-EP2311838A1; 41421-EP2270012A1; 41421-EP2270013A1; 41421-EP2305681A1; 41421-EP2311838A1; 89077-EP2270012A1; 89077-EP2270013A1; 89077-EP2305681A1; AB01273937-01; 281P233; Q415220; J-502393; L-Glutamic acid,3-d]pyrimidin-5-yl]ethyl]benzoyl]-; 1006872-74-7; N-({4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]phenyl}carbonyl)-L-glutamic acid; N-[4-[2(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo [2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid; N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7h-pyrrolo[2,3-d]pyrimi-din-5-yl)ethyl]benzoyl]l-glutamic acid; N-[4-[2-[2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl]ethyl]benzoyl]glutamic acid
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Molecular Type
Small molecule
Disease Pleural mesothelioma [ICD-11: 2C26] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability
Clearance
The drug present in the plasma can be removed from the body at the rate of 1.3 mL/min/kg
Elimination
80% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 3.5 hours
Metabolism
The drug is metabolized via the cytochrome P450 Enzymes
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.377 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 0.19%
Vd
The volume of distribution (Vd) of drug is 16.1 L
Water Solubility
The ability of drug to dissolve in water is measured as 90 mg/mL
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Formula
C20H21N5O6
PubChem CID
135410875
Canonical SMILES
C1=CC(=CC=C1CCC2=CNC3=C2C(=O)NC(=N3)N)C(=O)NC(CCC(=O)O)C(=O)O
InChI
1S/C20H21N5O6/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29)/t13-/m0/s1
InChIKey
WBXPDJSOTKVWSJ-ZDUSSCGKSA-N
CAS Number
CAS 137281-23-3
ChEBI ID
CHEBI:63616
TTD Drug ID
D0Y4GO
DrugBank ID
DB00642
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Metformin      Galega officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Metformin synergistic pemetrexed suppresses non-small-cell lung cancer cell proliferation and invasion in vitro.
Target and Pathway
Target(s) Candida thymidylate synthase (Candi TMP1)  Molecule Info  [3]
BioCyc Pyrimidine deoxyribonucleotides biosynthesis from CTP Click to Show/Hide
2 Pyrimidine deoxyribonucleotides de novo biosynthesis
3 Superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis
4 Superpathway of pyrimidine deoxyribonucleoside salvage
5 DTMP de novo biosynthesis (mitochondrial)
6 Pyrimidine deoxyribonucleosides salvage
KEGG Pathway Pyrimidine metabolism Click to Show/Hide
2 One carbon pool by folate
3 Metabolic pathways
Panther Pathway De novo pyrimidine deoxyribonucleotide biosynthesis Click to Show/Hide
2 Formyltetrahydroformate biosynthesis
Pathwhiz Pathway Pyrimidine Metabolism Click to Show/Hide
Pathway Interaction Database E2F transcription factor network Click to Show/Hide
Reactome E2F mediated regulation of DNA replication Click to Show/Hide
2 Pyrimidine biosynthesis
3 G1/S-Specific Transcription
WikiPathways Trans-sulfuration and one carbon metabolism Click to Show/Hide
2 Retinoblastoma (RB) in Cancer
3 One Carbon Metabolism
4 Integrated Pancreatic Cancer Pathway
5 miR-targeted genes in muscle cell - TarBase
6 miR-targeted genes in lymphocytes - TarBase
7 miR-targeted genes in leukocytes - TarBase
8 miR-targeted genes in epithelium - TarBase
9 Metabolism of nucleotides
10 Fluoropyrimidine Activity
References
Reference 1 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: 6837).
Reference 2 Metformin synergistic pemetrexed suppresses non-small-cell lung cancer cell proliferation and invasion in vitro. Cancer Med. 2017 Aug;6(8):1965-1975.
Reference 3 Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40.
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