Pemetrexed | CAS#137281-23-3 | nucleic acid synthesis inhibitor

MedKoo Cat#: 597222 | Name: Pemetrexed

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Pemetrexed is a multi-targeted antifolate chemotherapeutic agent primarily used in the treatment of malignant pleural mesothelioma and non-small cell lung cancer (NSCLC). It is a folate analog metabolic inhibitor that disrupts essential cellular processes required for DNA and RNA synthesis, leading to the inhibition of cancer cell proliferation. Pemetrexed demonstrates potent inhibitory activity against its target enzymes: Thymidylate Synthase (TS): IC₅₀ = ~1.3 nM; Dihydrofolate Reductase (DHFR): IC₅₀ = ~7.2 nM; Glycinamide Ribonucleotide Formyltransferase (GARFT): IC₅₀ = ~65 nM/ These values indicate that pemetrexed is most potent against TS, followed by DHFR and GARFT. Its strong inhibition of TS is a critical factor in its efficacy as an anticancer agent. Additionally, pemetrexed requires active cellular uptake via the reduced folate carrier (RFC) and folate receptor-mediated transport. Once inside the cell, it undergoes polyglutamation by folylpolyglutamate synthetase (FPGS), which enhances intracellular retention and prolongs enzyme inhibition.

Chemical Structure

Pemetrexed

CAS#137281-23-3 (free acid)

Theoretical Analysis

MedKoo Cat#: 597222

Name: Pemetrexed

CAS#: 137281-23-3 (free acid)

Chemical Formula: C20H21N5O6

Exact Mass: 427.1492

Molecular Weight: 427.41

Elemental Analysis: C, 56.20; H, 4.95; N, 16.39; O, 22.46

Price and Availability

Size	Price	Availability
100mg	USD 180.00	Ready to ship
250mg	USD 350.00	Ready to ship
500mg	USD 550.00	Ready to ship
1g	USD 850.00	2 weeks

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Related CAS #

357166-29-1 (sodium hydrate) 150399-23-8 (disodium) 137281-23-3 (free acid) 357166-30-4 (sodium 2.5 hydrate) 1851348-04-3 (tromethamine)

Synonym

Pemetrexed; Premetrexed; Alimta; NSC 698037; NSC-698037; NSC698037;

IUPAC/Chemical Name

(4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzoyl)-L-glutamic acid

InChi Key

WBXPDJSOTKVWSJ-ZDUSSCGKSA-N

InChi Code

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

SMILES Code

O=C(O)CC[C@@H](C(O)=O)NC(C1=CC=C(CCC2=CNC(NC(N)=N3)=C2C3=O)C=C1)=O

Appearance

Solid powder

Purity

>96% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A22M08B17

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Pemetrexed (LY231514) is an antifolate, the Ki values of the pentaglutamate of Pemetrexed (LY231514) are 1.3, 7.2, and 65 nM for inhibition of thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively.

In vitro activity:

In non-limited glucose condition, PEM (pemetrexed) alone led to the repression (72%) of protein synthesis confirming that the reduction in biomass in response to the drug could be attributed to the repression of protein translation. However, when PEM-treated cells were maintained in 1 mM glucose, the rate of protein synthesis was significantly higher than that in the glucose-starved condition alone. These results show that PEM treatment partially relieves translation inhibition caused by low glucose. Reference: Metabolites. 2021 Mar 26;11(4):198. https://pubmed.ncbi.nlm.nih.gov/33810430/

In vivo activity:

To define an appropriate oral dose of PMX (pemetrexed)/DCK-OP, the tumor inhibitory effect thereof was assessed using the A549 xenograft mouse model. After 24 days of treatment, PMX/DCK-OP exhibited a dose-dependent tumor inhibitory effect; tumor volumes fell by 40.1, 57.2, and 64.2% when PMX/DCK-OP was given at 10, 20, and 40 mg/kg PMX, respectively, compared to the control group (p < 0.001) (Figure 6A). After treatment, all tumors were excised and weighed (Figure 6B). The tumor weight graph well-reflected the tumor volume results; dose-dependent inhibition of tumor volume was apparent. PMX/DCK-OP at 40 mg/kg PMX maximally reduced tumor weight (by 59.1%) compared to the control (p < 0.001) (Figure 6C). Reference: Pharmaceutics. 2019 Jul 13;11(7):332. https://pubmed.ncbi.nlm.nih.gov/31337061/

	Solvent	mg/mL	mM
Solubility
	DMSO	125.9	294.60

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 427.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Piecyk M, Triki M, Laval PA, Dragic H, Cussonneau L, Fauvre J, Duret C, Aznar N, Renno T, Manié SN, Chaveroux C, FerraroPeyret C. Pemetrexed Hinders Translation Inhibition upon Low Glucose in Non-Small Cell Lung Cancer Cells. Metabolites. 2021 Mar 26;11(4):198. doi: 10.3390/metabo11040198. PMID: 33810430; PMCID: PMC8067050. 2. Li X, Song H, Kong F, Guo Y, Chen Y, Zhang L, Gao D, Zhao X, Zhang H. Pemetrexed exerts anticancer effects by inducing G0/G1-phase cell cycle arrest and activating the NOXA/Mcl-1 axis in human esophageal squamous cell carcinoma cells. Oncol Lett. 2019 Feb;17(2):1851-1858. doi: 10.3892/ol.2018.9753. Epub 2018 Nov 23. PMID: 30675247; PMCID: PMC6341790. 3. Maharjan R, Pangeni R, Jha SK, Choi JU, Chang KY, Choi YK, Park JW, Byun Y. Anti-Angiogenic Effect of Orally Available Pemetrexed for Metronomic Chemotherapy. Pharmaceutics. 2019 Jul 13;11(7):332. doi: 10.3390/pharmaceutics11070332. PMID: 31337061; PMCID: PMC6680992

In vitro protocol:

In vivo protocol:

1. Maharjan R, Pangeni R, Jha SK, Choi JU, Chang KY, Choi YK, Park JW, Byun Y. Anti-Angiogenic Effect of Orally Available Pemetrexed for Metronomic Chemotherapy. Pharmaceutics. 2019 Jul 13;11(7):332. doi: 10.3390/pharmaceutics11070332. PMID: 31337061; PMCID: PMC6680992

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Pemetrexed-Induced Syncope. Am J Ther. 2018 Jun 15. doi: 10.1097/MJT.0000000000000803. [Epub ahead of print] PubMed PMID: 29927772. 5: Pangeni R, Choi JU, Panthi VK, Byun Y, Park JW. Enhanced oral absorption of pemetrexed by ion-pairing complex formation with deoxycholic acid derivative and multiple nanoemulsion formulations: preparation, characterization, and in vivo oral bioavailability and anticancer effect. Int J Nanomedicine. 2018 Jun 6;13:3329-3351. doi: 10.2147/IJN.S167958. eCollection 2018. PubMed PMID: 29922055; PubMed Central PMCID: PMC5995301. 6: Xu D, Liang SQ, Yang H, Lüthi U, Riether C, Berezowska S, Marti TM, Hall SRR, Bruggmann R, Kocher GJ, Schmid RA, Peng RW. Increased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma. Br J Cancer. 2018 Jun 20. doi: 10.1038/s41416-018-0145-3. [Epub ahead of print] PubMed PMID: 29921948. 7: Xu H, Xu F, Zhu W, Ying J, Wang Y. Comparing first-line treatment patterns and clinical outcomes of patients with pan-negative advanced non-squamous non-small cell lung cancer. Thorac Cancer. 2018 Jun 19. doi: 10.1111/1759-7714.12777. [Epub ahead of print] PubMed PMID: 29917332. 8: Petri GL, Cascioferro S, Parrino B, Peters GJ, Diana P, Giovannetti E. Proton-coupled folate transporter as a biomarker of outcome to treatment for pleural mesothelioma. Pharmacogenomics. 2018 Jun 19. doi: 10.2217/pgs-2018-0071. [Epub ahead of print] PubMed PMID: 29916298. 9: Müller C, Guzik P, Siwowska K, Cohrs S, Schmid RM, Schibli R. Combining Albumin-Binding Properties and Interaction with Pemetrexed to Improve the Tissue Distribution of Radiofolates. Molecules. 2018 Jun 16;23(6). pii: E1465. doi: 10.3390/molecules23061465. PubMed PMID: 29914162. 10: Alshangiti A, Chandhoke G, Ellis PM. Antiangiogenic therapies in non-small-cell lung cancer. Curr Oncol. 2018 Jun;25(Suppl 1):S45-S58. doi: 10.3747/co.25.3747. Epub 2018 Jun 13. Review. PubMed PMID: 29910647; PubMed Central PMCID: PMC6001774. 11: Nishimoto K, Karayama M, Inui N, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inami N, Matsuura S, Kaida Y, Matsui T, Asada K, Matsuda H, Fujii M, Toyoshima M, Imokawa S, Suda T. Switch maintenance therapy with docetaxel and bevacizumab after induction therapy with cisplatin, pemetrexed, and bevacizumab in advanced non-squamous non-small cell lung cancer: a phase II study. Med Oncol. 2018 Jun 16;35(7):108. doi: 10.1007/s12032-018-1172-x. PubMed PMID: 29909581. 12: Carneiro-Leão L, Barzylovych V, Cernadas J. Pemetrexed anaphylaxis - an unusual suspect. J Allergy Clin Immunol Pract. 2018 Jun 13. pii: S2213-2198(18)30392-1. doi: 10.1016/j.jaip.2018.06.004. [Epub ahead of print] PubMed PMID: 29908333. 13: Mahmud F, Jeon OC, Alam F, Maharjan R, Choi JU, Park J, Lee S, Park JW, Lee DS, Byun Y. Oral pemetrexed facilitates low-dose metronomic therapy and enhances antitumor efficacy in lung cancer. J Control Release. 2018 Jun 13. pii: S0168-3659(18)30364-X. doi: 10.1016/j.jconrel.2018.06.018. [Epub ahead of print] PubMed PMID: 29908222. 14: Laslett NF, Park S, Masters GA, Biggs DD, Schneider CJ, Misleh JG, Suppiah K, Simpson PS, Grubbs S, Wozniak TF, Guarino M. Phase II study of carboplatin, pemetrexed, and bevacizumab in advanced nonsquamous non-small-cell lung cancer. Cancer Med. 2018 Jun 14. doi: 10.1002/cam4.1569. [Epub ahead of print] PubMed PMID: 29905018. 15: Bittoni MA, Arunachalam A, Li H, Camacho R, He J, Zhong Y, Lubiniecki GM, Carbone DP. Real-World Treatment Patterns, Overall Survival, and Occurrence and Costs of Adverse Events Associated With First-line Therapies for Medicare Patients 65 Years and Older With Advanced Non-small-cell Lung Cancer: A Retrospective Study. Clin Lung Cancer. 2018 May 7. pii: S1525-7304(18)30099-8. doi: 10.1016/j.cllc.2018.04.017. 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[Epub ahead of print] PubMed PMID: 29871545. 19: Severi L, Losi L, Fonda S, Taddia L, Gozzi G, Marverti G, Magni F, Chinello C, Stella M, Sheouli J, Braicu EI, Genovese F, Lauriola A, Marraccini C, Gualandi A, D'Arca D, Ferrari S, Costi MP. Proteomic and Bioinformatic Studies for the Characterization of Response to Pemetrexed in Platinum Drug Resistant Ovarian Cancer. Front Pharmacol. 2018 May 8;9:454. doi: 10.3389/fphar.2018.00454. eCollection 2018. PubMed PMID: 29867465; PubMed Central PMCID: PMC5952181. 20: Baxevanos P, Mountzios G. Novel chemotherapy regimens for advanced lung cancer: have we reached a plateau? Ann Transl Med. 2018 Apr;6(8):139. doi: 10.21037/atm.2018.04.04. Review. PubMed PMID: 29862228; PubMed Central PMCID: PMC5952027.