Pemetrexed Disodium Heptahydrate Chemical Properties

storage temp. 

2-8°C

solubility 

H2O: soluble30mg/mL, clear

form 

powder

color 

white to beige

Stability:

Stable for 1 year as supplied. Solutions in distilled water may be stored at -20° for up to 31month.

InChI

InChI=1/C20H21N5O6.Na.H2O.H/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);;1H2;/t13-;;;/s3

InChIKey

AEZRDYKQLPDYEH-YTCXBBKHNA-N

SMILES

C(C1=CNC2NC(N)=NC(=O)C1=2)CC1C=CC(C(=O)N[C@H](C(=O)O)CCC(=O)O)=CC=1.[NaH].O |&1:20,r|

Safety Information

Safety Statements 

24/25

WGK Germany 

3

HS Code 

29335990

Pemetrexed Disodium Heptahydrate Usage And Synthesis

Description

Pemetrexed Disodium Heptahydrate(357166-29-1) is a multi-targeted antifolate with antitumor activity. Its formal name is N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid disodium salt hydrate. It potently inhibits folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase (Ki?= 109 nM), dihydrofolate reductase (Ki?= 7 nM), glycinamide ribonucleotide formyltransferase (Ki?= 9.3 μM), and aminoimidazole carboxamide ribonucleotide formyltransferase (Ki?= 3.6 μM). It is a clinically useful anticancer agent. Indirectly activates the metabolic kinase AMPK and consequently influences the mTORC1 pathway in human carcinomas. Activation of AMPK is associated with pemetrexed resistance. Induces G0/G1-phase cell cycle arrest in esophageal squamous cell carcinoma cells.

Uses

Pemetrexed Disodium Heptahydrate is an chemotherapy drug for the treatment of pleural mesothelioma and non-small cell lung cancer. Pemetrexed Disodium Heptahydrate exhibit inhibitory activities towards thymidylate synthase as well as other folate dependent enzymes.

Uses

These Secondary Standards are qualified as Certified Reference Materials. These are suitable for use in several analytical applications including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements.

Definition

ChEBI: Pemetrexed disodium heptahydrate is an organic sodium salt that is the heptahydrate form of pemetrexed disodium. Inhibits thymidylate synthase (TS), 421 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). It has a role as an antimetabolite, an antineoplastic agent, an EC 1.5.1.3 (dihydrofolate reductase) inhibitor, an EC 2.1.1.45 (thymidylate synthase) inhibitor and an EC 2.1.2.2 (phosphoribosylglycinamide formyltransferase) inhibitor. It is an organic sodium salt and a hydrate. It contains a pemetrexed disodium.

General Description

Pemetrexed Disodium Heptahydrate secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
Pemetrexed is an anionic anticancer drug with a narrow therapeutic index. As a folate anti metabolite, it acts as an inhibitor of thymidylate synthase. It can act effectively against a broad-spectrum of solid tumors such as non-small-cell lung and breast cancers in clinical trials. It is also effective against both dihydrofolate reductase and glycinamide ribonucleotide formyl transferase.

Biochem/physiol Actions

Pemetrexed exhibits its activity against several tumors such as colorectal, breast, gastric, pancreatic, and cervical cancer. It acts as a substrate for multidrug resistance protein transporters.

in vitro

Pemetrexed (LY231514) disodium is a novel classical antifolate, the antitumor activity of which may result from simultaneous and multipie inhibition of several key folate-requiring enzymes via its polyglutamated metabolites. Pemetrexed (LY231514) is one of the best substrates that is known for the enzyme FPGS (Km=1.6 μM and Vmax/Km=621). It is likely that polyglutamation and the polyglutamated metabolites of LY231514 play profound roles in determining both the selectivity and the antitumor activity of this novel agent. Whereas LY23l5l4 only moderately inhibits TS (Ki=340 nM, recombinant mouse), the pentaglutamate of LY23l5l4 is 100-fold more potent (Ki=3.4 nM), making LY231514 one of the most potent folate-based TS inhibitors.

in vivo

The group of mice treated with PC61 plus Pemetrexed demonstrates statistically longer survival than other groups. In a survival analysis, significantly better survival is observed in the group of mice treated with PC61 plus Pemetrexed compare with those treated with PC61 alone, rat IgG plus Pemetrexed, or no treatment.

References

1) Shih?et al.?(1997),?LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes; Cancer Res.?57?1116 2) Hanauske?et al. (2001),?Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors; Oncologist?6?363 3) Rothbart?et al. (2010),?Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomas; Cancer Res.?70?10299 4) Qin?et al.?(2019),?AMPK activation induced in pemetrexed-treated cells is associated with development of drug resistance independently of target enzyme expression; Mol. Oncol.?13?1419 5) Li?et al.?(2019),?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.?17?1851

Pemetrexed Disodium Heptahydrate(357166-29-1)Related Product Information

• 4-(4-Hydroxybutyl)benzoic acid Methyl ester
• Pemetrexed disodium hemipentahydrate
• Methyl 4-bromobenzoate
• N-[4-[3-(2,6-DiaMino-1,4-dihydro-4-oxo-5-pyriMidinyl)-3-oxopropyl]benzoyl]-L-glutaMic Acid
• but-3-en-1-yl 4-methylbenzene-1-sulfonate
• PeMetrexed EP IMpurity A
• 4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid methyl ester
• 4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pymol[2,3-d]pyrimodin-5-yl)ethyl]benzoic acid
• 2,4-Diamino-6-hydroxypyrimidine
• 3-Butyn-1-ol
• Methyl 4-(4-hydroxybut-1-ynyl)benzoate
• N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid 1,5-diethyl ester
• N-[4-[2-(2-AMino-4,5,6,7-tetrahydro-4,6-dioxo-1H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl]benzoyl]-L-glutaMic Acid
• 3-Buten-1-ol
• Methyl 4-(4-oxobutyl)benzoate
• Pemetrexed Disodium
• Pemetrexed
• 4-[2’-(7’’-Deazaguanine)ethyl]benzoic Acid N-Hydroxysuccinimide Ester