Pemetrexed Disodium
Description References- Product Name
- Pemetrexed Disodium
- CAS No.
- 150399-23-8
- Chemical Name
- Pemetrexed Disodium
- Synonyms
- ALIMTA;LY-231514;PEMETREXED SODIUM;Alimt;AliMta disodiuM;LY231514 disodiuM;LY 231514 disodiuM;LY-231514 disodiuM;PeMetexed DisodiuM;Pemwtrexed Disodium
- CBNumber
- CB4385473
- Molecular Formula
- C20H22N5NaO6
- Formula Weight
- 451.41
- MOL File
- 150399-23-8.mol
Pemetrexed Disodium Property
- Melting point:
- 254-258°C (dec.)
- storage temp.
- Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
- solubility
- Methanol, Water
- form
- Solid
- color
- Off-White
- Stability:
- Hygroscopic
- InChI
- InChI=1/C20H21N5O6.Na.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);;/t13-;;/s3
- InChIKey
- UTEALKYVANXUSG-NVZXTOETNA-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] |&1:20,r|
- CAS DataBase Reference
- 150399-23-8(CAS DataBase Reference)
Safety
- Hazard Codes
- T;Xi,Xi,T
- Risk Statements
- 36/38-60-61-68
- Safety Statements
- 36/37/39-53
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H302Harmful if swallowed
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
N-Bromosuccinimide Price
- Product number
- A4390
- Product name
- Pemetrexed
- Packaging
- 1unit
- Price
- $28
- Updated
- 2021/12/16
- Product number
- A4390
- Product name
- Pemetrexed
- Packaging
- 100mg
- Price
- $50
- Updated
- 2021/12/16
- Product number
- A4390
- Product name
- Pemetrexed
- Packaging
- 10mM(in 1mL DMSO)
- Price
- $50
- Updated
- 2021/12/16
- Product number
- BP164243
- Product name
- Pemetrexed disodium
- Packaging
- 50mg
- Price
- $50
- Updated
- 2021/12/16
- Product number
- A4390
- Product name
- Pemetrexed
- Packaging
- 200mg
- Price
- $80
- Updated
- 2021/12/16
Pemetrexed Disodium Chemical Properties,Usage,Production
Description
Pemetrexed disodium (marketed as ALIMTA®, “pemetrexed”) is a novel, multi-targeted antifolate. It suppresses tumor growth by impeding both DNA synthesis and folate metabolism. Pemetrexed disodium has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck.
Pemetrexed disodium is approved to be used alone or with other drugs to treat malignant pleural mesothelioma in patients who cannot be treated with surgery and non-small cell lung cancer (certain types) in patients whose disease is locally advanced or has metastasized (spread to other parts of the body). Pemetrexed disodium is also being studied in the treatment of other types of cancer.
References
[1] https://www.cancer.gov/about-cancer/treatment/drugs/pemetrexeddisodium
[2] Axel-R. Hanauske, V. Chen P. Paoletti, C. Niyikiza (2001) Pemetrexed Disodium: A Novel Antifolate Clinically Active Against Multiple Solid Tumors, The Oncologist, 6, 363-373
Description
Pemetrexed, a pyrrolo[2,3-d]pyrimidine-based antifolate that disrupts cell replication by inhibiting multiple folate-dependent metabolic processes, was initially developed and launched in the US for the treatment of malignant pleural mesothelioma in conjunction with cisplatin. Patients who are not candidates for surgery may benefit from this combination therapy. Clinical data demonstrated that the median overall survival time increased to 12.1 months, compared with 9.3 months for patients receiving cisplatin alone. In August of 2004, the FDA also approved pemetrexed as a second-line treatment of non-small-cell lung cancer (NSCLC). While median survival is comparable to the standard second-line treatment docetaxel, the improved toxicity profile (significant reduction in neutropenia) accelerated the approval for NSCLC. Its effectiveness as an anticancer drug is derived from its ability to gain internal cell access via the reduced folate carrier and membrane folate binding protein transport systems. Once inside, pemetrexed undergoes polyglutamation, and the resultant polyglutamate forms (predominantly the pentaglutamate) inhibit the folate-dependent enzymes thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). Against recombinant human TS, pemetrexed has a Ki of 109nM while the triglutamate and pentaglutamate forms have Ki values of 1.6nM and 1.3 nM, respectively. All forms of pemetrexed display similar potency against recombinant human DHFR (7 nM), but the pentaglutamate form is significantly more potent against recombinant murine GARFT than the parent (Ki=65nM versus 9.3μM). The selectivity of pemetrexed may be explained by the fact that polyglutamation is more likely to occur in cancer cells compared to normal cells while its prolonged duration of action may be attributed to decreased cellular efflux of the polyglutamate forms. While several different routes have provided pemetrexed, one of the most efficient exploits the propensity of 2,6-diamino-3Hpyrimidin- 4-one to undergo Michael additions at its unsubstituted C-5 position. Using ethyl 4-(4-nitrobut-3-enyl)benzoate as the Michael acceptor, the resulting adduct is then converted to the ultimate precursor for glutamyl coupling via a onepot, three-step process (Nef reaction to transform the nitro to the aldehyde, intramolecular condensation to afford the pyrrole, and saponification of the ethyl ester). A typical treatment regimen involves intravenous administration of pemetrexed, infused over ten minutes, at a dose of 500mg/m2 followed by a thirty minute wash-out period and then cisplatin intravenously over two hours at a dose of 75mg/m2. Both drugs are given on Day 1 of a 21-day cycle. In order to reduce treatment-related hematological and GI toxicity, patients are instructed to take folic acid and vitamin B12 as a prophylactic measure. Pretreatment with a corticosteroid is also recommended to prevent possible skin rashes. Pemetrexed is primarily excreted intact in the urine, with 70–90% of the dose being recovered within 24 hours of administration. The half-life of pemetrexed is 3.5 hours in patients with normal renal function, and the total systemic clearance is 91.8mL/min. As expected, clearance decreases as renal impairment increases. The drug’s plasma protein binding is 81%, and it has a steady state volume of distribution of 16.1 L. The pharmacokinetics of pemetrexed is linear with dose and remains unchanged over multiple treatment cycles. While in vitro studies suggest that pemetrexed would not interfere with drugs metabolized by CYP3A4, CYP2D6, CYP2C9, and CYP1A2, ibuprofen (400mg q.d.) does reduce pemetrexed clearance by 20%. Caution should, therefore, be taken when administering pemetrexed concurrently with ibuprofen to patients with renal insufficiency and should not be given at all to patients whose creatinine clearance is ＜45mL/min. .
Chemical Properties
Crystalline Solid
Originator
Eli Lilly (US)
Uses
Multitargeted antifolate; inhibits thymidylate synthase as well as other folate dependent enzymes. Antineoplastic.
Uses
Pemetrexed is a novel antifolate and antimetabolite for TS, DHFR and GARFT with Ki of 1.3 nM, 7.2 nM and 65 nM, respectively
Definition
ChEBI: An organic sodium salt that is the disodium salt of N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid. Inhibits thymidylate synthase (TS), 4 1 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT).
brand name
Alimta (Lilly).
General Description
The drug is available in a 100-mg sterile vial for IV use. Thedrug appears to be effective against a range of tumors includingmesothelioma, NSCLC, colorectal cancer, bladdercancer, and lung cancer. The mechanism of action involvesinhibition of TS resulting in inhibition of thymidylate andDNA synthesis. This drug is a pyrrolopyrimidine analog offolate with antifolate activity. Resistance can occur by increasedexpression of TS, decreased binding affinity for TS,or decreased drug transport into cells. The drug is administeredonly via the IV route and distributes to all tissues.Cellular activation to the more potent polyglutamated formsoccurs, and the majority of the dose is excreted unchangedin the urine. The drug interaction and toxicity profiles aresimilar to that of methotrexate.
Mechanism of action
Like methotrexate, it is actively transported into tumor cells through reduced folate carriers and, in polyglutamated form, inhibits the synthesis of pyrimidine and purine-based nucletotides by disrupting folatedependent metabolic processes . In addition to DHFR, this pyrrolopyrimidine-based inhibitor binds tightly to thymidylate synthase and GAR transformylase.
Clinical Use
Pemetrexed is a novel multitarget antifolate used by the IV route for the treatment of advanced or metastatic nonsmall cell lung cancer and in combination with cisplatin in malignant pleural mesothelioma.
Side effects
Patients on pemetrexed must take folate and vitamin B12 supplements to reduce the risk of bone marrow suppression (neutropenia, thrombocytopenia, and anemia) and GI side effects. Pretreatment with corticosteroids can reduce the risk of drug-induced skin rash. Pemetrexed has a half-life of 3.5 hours and is excreted primarily unchanged via the kidneys. Significant cross-resistance has been noted between pemetrexed and other pyrimidine and folate antagonists.
Synthesis
A number of papers outlining the syntheses of pemetrexed and related analogs have appeared. A practical and scalable synthetic route is depicted in Scheme 9. Palladium (0) coupling of methyl 4-bromobenzoate (57) with 3-butyn-1-ol (58) gave crystalline 59, which was then reduced over palladium on carbon in DCM to give alcohol 60. Filtration of the catalyst afforded a DCM solution of alcohol 60, which was utilized directly in a TEMPO-catalyzed sodium hypochlorite oxidation, providing known aldehyde 61 without isolation. Addition of 5,5-dibromobarbituric acid (DBBA) and catalytic amount of HBr in acetic acid to the DCM solution of 61 effected the conversion to a-bromoaldehyde 62. After aqueous work-up, the solution was concentrated and diluted with acetonitrile to exchange solvents. Addition of commercially available 2,4-diamino-6-hydroxypyrimidine (63), aqueous sodium acetate and heating to 45??C resulted in cyclic condensation and precipitation of pyrrolo[2,3- d]pyrimidine 64 from the reaction mixture in 67% yield based on 60. Saponification of 64 with aqueous sodium hydroxide followed by acidification afforded the carboxylic acid derivative 65, which was elaborated to 66 by chlorodimethoxytriazine active ester coupling method. Reaction of 65 with 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) in the presence of N-methylmorpholine in DMF solution followed by reaction of the resulting dimethoxy-s-triazinyl ester with diethyl L-glutamate afforded crude 66, which was isolated via crystallization as pTSA salt 67. Saponification of 67 with aqueous sodium hydroxide followed by acidification with HCl gave pemetrexed as the free acid, which was crystallized as disodium salt form.
target
MEK | ERK
Drug interactions
Potentially hazardous interactions with other drugs
Antimalarials: antifolate effect increased by
pyrimethamine.
Antipsychotics: avoid with clozapine, increased risk
of agranulocytosis.
Nephrotoxic agents: may reduce clearance of
pemetrexed - use with caution.
Live vaccines: avoid use; YELLOW
FEVER VACCINE ABSOLUTELY
CONTRAINDICATED.
Metabolism
Pemetrexed undergoes minimal hepatic metabolism, and about 70-90% of a dose is eliminated unchanged in the urine within 24 hours. In vitro studies indicate that pemetrexed is actively secreted by OAT3 (organic anion transporter).
Pemetrexed Disodium Preparation Products And Raw materials
Raw materials
Preparation Products
Pemetrexed Disodium Suppliers
- Tel
- 13585114296
- liuhongwei@ask-pharm.com
- Country
- China
- ProdList
- 1122
- Advantage
- 58
- Tel
- 18115209001
- 3425423740@qq.com
- Country
- China
- ProdList
- 53
- Advantage
- 58
- Tel
- 025-85566666-8770 15195996671
- API@simcere.com
- Country
- China
- ProdList
- 19
- Advantage
- 58
- Tel
- 18036652731
- 476682145@qq.com
- Country
- China
- ProdList
- 55
- Advantage
- 58
- Tel
- 18210857532; 18210857532
- Fax
- 86-10-82849933
- jkinfo@jkchemical.com
- Country
- China
- ProdList
- 96815
- Advantage
- 76
- Tel
- +86-21-20908456
- Fax
- 021-58180499
- sales@BioChemBest.com
- Country
- China
- ProdList
- 6003
- Advantage
- 61
- Tel
- 18515581800 18501085097
- Fax
- 010-89508210
- sales.bj@hwrkchemical.com
- Country
- China
- ProdList
- 9400
- Advantage
- 55
- Tel
- 021-50135380
- shchemsky@sina.com
- Country
- China
- ProdList
- 32321
- Advantage
- 50
- Tel
- 15527768836
- 1791901229@qq.com
- Country
- China
- ProdList
- 6950
- Advantage
- 52
- Tel
- 18270980682
- Fax
- 021 51613951
- mlcheng@sunwaypharm.cn
- Country
- China
- ProdList
- 8669
- Advantage
- 57
- Tel
- 0571-82693216
- Fax
- +86-571-82880190
- info@yuhaochemical.com
- Country
- China
- ProdList
- 6387
- Advantage
- 52
- Tel
- 027-59207852 13308628970
- Fax
- QQ3130921841
- buy@fortunachem.com
- Country
- China
- ProdList
- 2744
- Advantage
- 58
- Tel
- 86-21-34053660
- Fax
- 86-21-34053661
- sale@labgogo.com
- Country
- China
- ProdList
- 9865
- Advantage
- 52
- Tel
- 010-56205725
- Fax
- 010-65763397
- waley188@sohu.com
- Country
- China
- ProdList
- 12335
- Advantage
- 58
- Tel
- 4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988
- Fax
- +86-27-87599188
- Country
- China
- ProdList
- 1493
- Advantage
- 55
- Tel
- +86 (21) 5811-6473 5811-6475
- Fax
- +86 (21) 6129-4103
- sales@koutingchina.com
- Country
- China
- ProdList
- 496
- Advantage
- 60
- Tel
- 021-58950125
- Fax
- (86) 21-58955996
- info@chemexpress.com
- Country
- China
- ProdList
- 7552
- Advantage
- 61
- Tel
- 400-6206333 13167063860
- Fax
- 021-50323701
- anhua.mao@aladdin-e.com
- Country
- China
- ProdList
- 25003
- Advantage
- 65
- Tel
- +86(0)21 60484900
- Fax
- +86(0)21 60484900
- Country
- China
- ProdList
- 764
- Advantage
- 50
- Tel
- 025-57798810
- Fax
- 025-57019371
- sales@sunlidabio.com
- Country
- China
- ProdList
- 3239
- Advantage
- 55
- Tel
- 021-021-33632979 15002134094
- Fax
- 021-33632979
- marketing@targetmol.com
- Country
- China
- ProdList
- 7783
- Advantage
- 58
- Tel
- 021-61119791,13386096464
- Fax
- 021-50190009
- bzswkf@foxmail.com
- Country
- China
- ProdList
- 3921
- Advantage
- 50
- Tel
- 027-27-81302488 15972195220
- Fax
- 027-81302088
- info@dkybpc.com
- Country
- China
- ProdList
- 1758
- Advantage
- 58
- Tel
- 13971561712, 13995564702, 027-50664929
- Fax
- 027-50664927
- hbeixys2001@163.com
- Country
- China
- ProdList
- 3120
- Advantage
- 55
- Tel
- 0554-2106669
- Fax
- 0554-2666215
- sales1@kedichem.com
- Country
- China
- ProdList
- 4924
- Advantage
- 55
- Tel
- 0755-0755-66853366 13670046396
- Fax
- 0755-28363542
- sales@chem-strong.com
- Country
- China
- ProdList
- 18333
- Advantage
- 56
- Tel
- 400-1166-196 13458535857
- Fax
- QQ：800101999
- cdhxsj@163.com
- Country
- China
- ProdList
- 13350
- Advantage
- 58
- Tel
- 0510-85629785 18013409632
- Fax
- 051085625359
- sales@reading-chemicals.com
- Country
- China
- ProdList
- 15178
- Advantage
- 58
- Tel
- 0512-87182056 18013166090
- Fax
- 0512-87182056
- lingling.qi@yacoo.com.cn
- Country
- China
- ProdList
- 6295
- Advantage
- 60
- Tel
- 027-59262863 13277907145 3091977954
- Fax
- 027-59420980
- Country
- China
- ProdList
- 4942
- Advantage
- 58
- Tel
- 021-60345187 13671753212
- Fax
- 021-34702061
- lzz841106@aliyun.com
- Country
- China
- ProdList
- 10263
- Advantage
- 55
- Tel
- 15221275939
- Fax
- 021-50706099
- shenlinxing@macklin.cn
- Country
- China
- ProdList
- 15873
- Advantage
- 55
- Tel
- 027-59420981,18702770802
- Fax
- 027-83322098
- Country
- China
- ProdList
- 1975
- Advantage
- 50
- Tel
- 010-1234567 18521000990
- Fax
- 86-021-33275113
- sonyuanchemical@163.com
- Country
- China
- ProdList
- 6479
- Advantage
- 50
- Tel
- 025-58849295 18951903616;
- Fax
- 025-68650336
- info@adooq.cn
- Country
- China
- ProdList
- 2990
- Advantage
- 60
- Tel
- +86 (21) 61124340
- Fax
- +86 (21) 6129-4103
- Country
- China
- ProdList
- 9756
- Advantage
- 58
- Tel
- 027-59599241 18871490274
- Fax
- 027-59599241
- 1400878000@qq.com
- Country
- China
- ProdList
- 9858
- Advantage
- 58
- Tel
- 020-38082199,29065168,38082986,29878298,29866629,4000192398
- Fax
- +86 (20)38082986
- Country
- China
- ProdList
- 830
- Advantage
- 60
- Tel
- 86(21)68097365
- Fax
- 86(21)33321566
- sales@anpharma.net
- Country
- China
- ProdList
- 4891
- Advantage
- 55
- Tel
- 18068075658
- Fax
- -
- sales@chempioneer.com
- Country
- China
- ProdList
- 1811
- Advantage
- 58
- Tel
- 0512-63009836 18994340901
- Fax
- 0512-63006936
- helen@struchem.com
- Country
- China
- ProdList
- 3981
- Advantage
- 60
- Tel
- Fax
- -
- eric_feng1954@126.com
- Country
- China
- ProdList
- 9248
- Advantage
- 55
- Tel
- 025-85090179
- Fax
- 025-85090192
- normal@ask-pharm.com
- Country
- China
- ProdList
- 15
- Advantage
- 58
- Tel
- 18620099427
- Fax
- +86-20-62619665
- amy@howeipharm.com
- Country
- China
- ProdList
- 6687
- Advantage
- 55
- Tel
- 028-86040038 13980902949;
- Fax
- 028-85149890
- market@dingdangchem.com
- Country
- China
- ProdList
- 1853
- Advantage
- 55
- Tel
- 025-87193546 18652950785
- Fax
- 025-87193546
- chemweiao@163.com
- Country
- China
- ProdList
- 9021
- Advantage
- 60
- Tel
- +86 (531) 8099-2215
- Fax
- +86 (531) 8099-2215
- putubio@outlook.com
- Country
- China
- ProdList
- 1261
- Advantage
- 55
- Tel
- +86-400-851-9921
- Fax
- +86-10-82826195
- sales@pharmacodia.com
- Country
- China
- ProdList
- 2317
- Advantage
- 55
- Tel
- 526763801 13301653310
- Fax
- +86-21-51619052
- 526763801@qq.com
- Country
- China
- ProdList
- 9279
- Advantage
- 55
- Tel
- 020-61288194 61288195
- Fax
- 020-61288700
- 505721671@qq.com
- Country
- China
- ProdList
- 3866
- Advantage
- 58
View Lastest Price from Pemetrexed Disodium manufacturers
- Product
- Pemetrexed Disodium 150399-23-8
- Price
- US $5.00-0.50/KG
- Min. Order
- 1KG
- Purity
- 99% hplc
- Supply Ability
- 500TONS
- Release date
- 2025-05-08
- Product
- Pemetrexed disodium 150399-23-8
- Price
- US $0.00/g/Bag
- Min. Order
- 1g
- Purity
- 99%min
- Supply Ability
- 10kg
- Release date
- 2021-10-18
- Product
- Pemetrexed Disodium 150399-23-8
- Price
- US $20.00-80.00/mg
- Min. Order
- 50mg
- Purity
- 99%
- Supply Ability
- 50
- Release date
- 2024-07-10