Pemetrexed disodium | CAS#150399-23-8 | CAS#357166-29-1 | 150399-23-8 | 137281-23-3 | thymidylate synthase

MedKoo Cat#: 100710 | Name: Pemetrexed disodium heptahydrate

Description:

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

Pemtrexed disodium is the disodium salt of a synthetic pyrimidine-based antifolate. Pemetrexed binds to and inhibits the enzyme thymidylate synthase (TS) which catalyses the methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP), an essential precursor in DNA synthesis.

Chemical Structure

Pemetrexed disodium heptahydrate

CAS#357166-29-1 (sodium hydrate)

Theoretical Analysis

MedKoo Cat#: 100710

Name: Pemetrexed disodium heptahydrate

CAS#: 357166-29-1 (sodium hydrate)

Chemical Formula: C20H33N5Na2O13

Exact Mass: 0.0000

Molecular Weight: 597.49

Elemental Analysis: C, 40.21; H, 5.57; N, 11.72; Na, 7.70; O, 34.81

Price and Availability

Size	Price	Availability
1g	USD 150.00	Ready to ship
2g	USD 250.00	Ready to ship
5g	USD 550.00	Ready to ship
10g	USD 950.00	Ready to ship

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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

LY231514; LY-231514; LY 231514; Pemetrexed, US brand name: ALIMTA. Abbreviation: MTA.

IUPAC/Chemical Name

sodium (S)-2-(4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioate heptahydrate.

InChi Key

QJVSMHJWAOSBMD-MYXYZBIASA-L

InChi Code

InChI=1S/C20H21N5O6.2Na.7H2O/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);;;7*1H2/q;2*+1;;;;;;;/p-2/t13-;;;;;;;;;/m0........./s1

SMILES Code

O=C([O-])[C@@H](NC(C1=CC=C(CCC2=CNC(NC(N)=N3)=C2C3=O)C=C1)=O)CCC([O-])=O.[H]O[H].[H]O[H].[H]O[H].[H]O[H].[H]O[H].[H]O[H].[H]O[H].[Na+].[Na+]

Appearance

white solid powder

Purity

>98% (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

Very poorly soluble in DMSO; soluble in water at 100 mg/mL; very poorly soluble in ethanol.

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO or water.

Stock Solution Storage

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

HS Tariff Code

2934.99.9001

More Info

Related CAS# CAS#357166-29-1 (Pemetrexed disodium heptahydrate); CAS#150399-23-8 (Pemetrexed Disodium) CAS#137281-23-3 (Pemetrexed) Pemetrexed (fre acid) Chemical Formula: C20H21N5O6 Exact Mass: 427.1492 Molecular Weight: 427.4170 Elemental Analysis: C, 56.20; H, 4.95; N, 16.39; O, 22.46

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC60317

View CoA: current batch, Lot#YYP30820

QC Data

View QC data: current batch, Lot#YYP30820

View QC data: current batch, Lot#TZC60317

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Pemtrexed disodium is the disodium salt of a synthetic pyrimidine-based antifolate that binds to and inhibits the enzyme thymidylate synthase (TS).

In vitro activity:

In this study, the effects of PEM (pemetrexed) on the sensitivity of human NSCLC cells to two different types of cytotoxic immune cells were examined. The expression of NK receptor ligands, including MICA/B and ULBP1/2/5/6, on PC9 and A549 cells after PEM treatment were exmained. The results showed that although ULBP2/5/6 expression on both cell lines was upregulated by PEM treatment, PEM treatment significantly increased the expression of ULBP2/5/6 on PC9 cells; the increased expression of ULBP2/5/6 on A549 cells was not significant (Figure 5A and B). Because the antibody against ULBP2/5/6 was unable to discriminate among ULBP molecules, quantitative RT‐PCR (RT‐qPCR) was performed and found that PEM treatment mainly increased the mRNA expression of ULBP2/5/6 in PC9 and A549 cells (Figure 5C). In addition, given that PEM can induce senescence in lung cancer cells 13 and that NK receptor ligands on senescent cells can be targets in immunosurveillance, 20 senescence in PEM‐treated cancer cell lines was next examined. On confocal imaging, PEM treatment increased the expression of SA β‐gal (Figure 5D). In addition, PEM treatment increased the expression of p21 in A549 cells (Figure 5E) and the production of IL‐6 by PC9 cells and IL‐8 by A549 cells (Figure 5F). The production of IL‐8 by PC9 cells was slightly but significantly decreased by PEM treatment. The expression of SA β‐gal, growth arrest and production of inflammatory cytokines are features of senescent cells; these results suggest that PEM can increase the expression of NK receptor ligands, ULBP, in association with the induction of senescence, and increase the sensitivity to NK cells. Reference: Cancer Sci. 2020 Jun;111(6):1910-1920. https://pubmed.ncbi.nlm.nih.gov/32232903/

In vivo activity:

To characterize the effects of pemetrexed on intratumor immune response, initial experiments were performed in immunocompetent syngeneic mouse tumor models. To meet the research objective, the models had to meet 2 prerequisites: (i) demonstrate sensitivity to pemetrexed and (ii) responsiveness to PD(L)1 blockade. MC38 tumors were responsive to pemetrexed at 50 and 100 mg/kg (% tumor growth inhibition of 30% and 52%, respectively; Fig. 1A). Tumors collected after 14 days of pemetrexed therapy were analyzed for changes in immune cell frequencies using flow cytometry. These analyses revealed that pemetrexed increased the frequency of total intratumoral leukocytes (live CD45+cells) at both doses, with a trend towards an increased percentage of total CD3+and cycling (Ki67+) CD8+cells, particularly at 50 mg/kg (Fig. 1B–E). Molecular analysis of tumor samples using a custom-made immune profiling QuantiGene Plex (QGP) gene expression panel revealed that treatment with pemetrexed at 50 and 100 mg/kg promoted a Tcell inflamed phenotype, exemplified by upregulation of T-cell activation-associated genes including Pdcd1, Cd8b, Prf1, and Gzma (Fig. 1G). Beyond these changes, one of the genes most significantly modulated by pemetrexed treatment was Vegfc, which encodes vascular endothelial growth factor C (VEGF-C), a key regulator of lymphangiogenesis. Nos2, which encodes inducible nitric oxide synthase, is produced by myeloid-derived suppressor cells (MDSC) and DCs, was downregulated at both dose levels, suggesting that pemetrexed could potentially negatively impact myeloid cell subsets (Fig. 1G). Collectively, these results suggest that pemetrexed influences the functionality rather than frequency of myeloid cells. Reference: Clin Cancer Res. 2019 Dec 1;25(23):7175-7188. https://pubmed.ncbi.nlm.nih.gov/31409612/

	Solvent	mg/mL	mM
Solubility
	H2O	100.0	167.40

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 597.49 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. Schaer DA, Geeganage S, Amaladas N, Lu ZH, Rasmussen ER, Sonyi A, Chin D, Capen A, Li Y, Meyer CM, Jones BD, Huang X, Luo S, Carpenito C, Roth KD, Nikolayev A, Tan B, Brahmachary M, Chodavarapu K, Dorsey FC, Manro JR, Doman TN, Donoho GP, Surguladze D, Hall GE, Kalos M, Novosiadly RD. The Folate Pathway Inhibitor Pemetrexed Pleiotropically Enhances Effects of Cancer Immunotherapy. Clin Cancer Res. 2019 Dec 1;25(23):7175-7188. doi: 10.1158/1078-0432.CCR-19-0433. Epub 2019 Aug 13. PMID: 31409612. 2. Okimoto T, Kotani H, Iida Y, Koyanagi A, Tanino R, Tsubata Y, Isobe T, Harada M. Pemetrexed sensitizes human lung cancer cells to cytotoxic immune cells. Cancer Sci. 2020 Jun;111(6):1910-1920. doi: 10.1111/cas.14401. Epub 2020 Apr 22. PMID: 32232903; PMCID: PMC7293070. 3. Müller C, Schibli R, Krenning EP, de Jong M. Pemetrexed improves tumor selectivity of 111In-DTPA-folate in mice with folate receptor-positive ovarian cancer. J Nucl Med. 2008 Apr;49(4):623-9. doi: 10.2967/jnumed.107.047704. Epub 2008 Mar 14. PMID: 18344429.

In vitro protocol:

In vivo protocol:

1. Müller C, Schibli R, Krenning EP, de Jong M. Pemetrexed improves tumor selectivity of 111In-DTPA-folate in mice with folate receptor-positive ovarian cancer. J Nucl Med. 2008 Apr;49(4):623-9. doi: 10.2967/jnumed.107.047704. Epub 2008 Mar 14. PMID: 18344429. 2. Schaer DA, Geeganage S, Amaladas N, Lu ZH, Rasmussen ER, Sonyi A, Chin D, Capen A, Li Y, Meyer CM, Jones BD, Huang X, Luo S, Carpenito C, Roth KD, Nikolayev A, Tan B, Brahmachary M, Chodavarapu K, Dorsey FC, Manro JR, Doman TN, Donoho GP, Surguladze D, Hall GE, Kalos M, Novosiadly RD. The Folate Pathway Inhibitor Pemetrexed Pleiotropically Enhances Effects of Cancer Immunotherapy. Clin Cancer Res. 2019 Dec 1;25(23):7175-7188. doi: 10.1158/1078-0432.CCR-19-0433. Epub 2019 Aug 13. PMID: 31409612.

1: Liu Y, Yin TJ, Zhou R, Zhou S, Fan L, Zhang RG. Expression of thymidylate synthase predicts clinical outcomes of pemetrexed-containing chemotherapy for non-small-cell lung cancer: a systemic review and meta-analysis. Cancer Chemother Pharmacol. 2013 Nov;72(5):1125-32. doi: 10.1007/s00280-013-2299-2. Epub 2013 Sep 26. Review. PubMed PMID: 24067998. 2: Boons CC, VAN Tulder MW, Burgers JA, Beckeringh JJ, Wagner C, Hugtenburg JG. The value of pemetrexed for the treatment of malignant pleural mesothelioma: a comprehensive review. Anticancer Res. 2013 Sep;33(9):3553-61. Review. PubMed PMID: 24023280. 3: Genova C, Rijavec E, Truini A, Coco S, Sini C, Barletta G, Dal Bello MG, Alama A, Savarino G, Pronzato P, Boccardo F, Grossi F. Pemetrexed for the treatment of non-small cell lung cancer. Expert Opin Pharmacother. 2013 Aug;14(11):1545-58. doi: 10.1517/14656566.2013.802774. Epub 2013 May 17. Review. PubMed PMID: 23683110. 4: Tomasini P, Greillier L, Khobta N, Barlesi F. The place of pemetrexed in the management of non-small-cell lung cancer patients. Expert Rev Anticancer Ther. 2013 Mar;13(3):257-66. doi: 10.1586/era.12.171. Review. PubMed PMID: 23477511. 5: Argiris A, Pennella E, Koustenis A, Hossain AM, Obasaju CK. Pemetrexed in head and neck cancer: a systematic review. Oral Oncol. 2013 Jun;49(6):492-501. doi: 10.1016/j.oraloncology.2013.01.007. Epub 2013 Mar 7. Review. PubMed PMID: 23466170. 6: Gilani SN, Gridley R, Searle G, Jegannathen A. Malignant peritoneal mesothelioma (MPM) who responded to rechallenge with cisplatin and pemetrexed with current literature review. BMJ Case Rep. 2013 Jan 3;2013. pii: bcr2012007786. doi: 10.1136/bcr-2012-007786. Review. PubMed PMID: 23291819. 7: Qi WX, Tang LN, He AN, Shen Z, Lin F, Yao Y. Erlotinib and pemetrexed as maintenance therapy for advanced non-small-cell lung cancer: a systematic review and indirect comparison. Curr Med Res Opin. 2012 Apr;28(4):643-50. doi: 10.1185/03007995.2012.675880. Epub 2012 Mar 29. Review. PubMed PMID: 22414178. 8: Morotti M, Valenzano Menada M, Venturini PL, Mammoliti S, Ferrero S. Pemetrexed disodium in ovarian cancer treatment. Expert Opin Investig Drugs. 2012 Apr;21(4):437-49. doi: 10.1517/13543784.2012.661714. Epub 2012 Feb 13. Review. PubMed PMID: 22324304. 9: Qi WX, Tang LN, He AN, Shen Z, Yao Y. Effectiveness and safety of pemetrexed-based doublet versus pemetrexed alone as second-line treatment for advanced non-small-cell lung cancer: a systematic review and meta-analysis. J Cancer Res Clin Oncol. 2012 May;138(5):745-51. doi: 10.1007/s00432-012-1155-9. Epub 2012 Jan 19. Review. PubMed PMID: 22258853. 10: SÃ¸rensen JB. Pharmacokinetic evaluation of pemetrexed. Expert Opin Drug Metab Toxicol. 2011 Jul;7(7):919-28. doi: 10.1517/17425255.2011.587411. Epub 2011 May 21. Review. PubMed PMID: 21599552.