106400-81-1 Usage
Description
Lometrexol, also known as Lometrexol hydrate, is a folate analog antimetabolite with antineoplastic activity. It is a potent inhibitor of glycinamide ribonucleotide formyltransferase (GARFTase), an enzyme essential for de novo purine synthesis. Lometrexol works by inhibiting GARFT at nanomolar concentrations, which in turn prevents de novo purine synthesis, inhibits DNA synthesis, arrests cells in the S phase of the cell cycle, and ultimately inhibits tumor cell proliferation.
Uses
Used in Pharmaceutical Industry:
Lometrexol is used as an antineoplastic agent for its ability to inhibit tumor cell proliferation by targeting the GARFTase enzyme, which is crucial for de novo purine synthesis. This makes it a valuable compound in the development of cancer treatments.
Used in Cancer Research:
In the field of cancer research, Lometrexol is used as a potent inhibitor of human GARFTase to study the biological activity and its effects on cancer cell growth and proliferation. This helps researchers understand the mechanisms of action and potential therapeutic applications of Lometrexol in cancer treatment.
Used in Drug Development:
Lometrexol is utilized in the development of new drugs and therapies targeting cancer cells. Its ability to inhibit GARFTase makes it a promising candidate for the creation of novel anticancer drugs that can potentially improve patient outcomes and survival rates.
Biochem/physiol Actions
Glycinamide Ribonucleotide Formyltransferase (GARFTase) is a folate-dependent enzyme required for de novo purine synthesis. Lometrexate is a potent inhibitor of GARFTase, but does not interfere with enzymes involved in the synthesis of folate. Lometrexerol has been tested clinically for the treatment of various cancers as an anti-folate like agent, similar to methotrexate. Treatment with lometrexol rapidly decreases ATP and GTP levels, cell cycle arrest and induces apoptosis. Although depletion of nucleotide pools induces p53 expression, lometrexol is cytotoxic in both wild-type and mutant p53 expressing tumor cells. Lometrexol is cytotoxic in CCRF-CEm leukemia cells with an IC50 of 2.9 nM.
Check Digit Verification of cas no
The CAS Registry Mumber 106400-81-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,6,4,0 and 0 respectively; the second part has 2 digits, 8 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 106400-81:
(8*1)+(7*0)+(6*6)+(5*4)+(4*0)+(3*0)+(2*8)+(1*1)=81
81 % 10 = 1
So 106400-81-1 is a valid CAS Registry Number.
InChI:InChI=1/C21H25N5O6/c22-21-25-17-14(19(30)26-21)9-12(10-23-17)2-1-11-3-5-13(6-4-11)18(29)24-15(20(31)32)7-8-16(27)28/h3-6,12,15H,1-2,7-10H2,(H,24,29)(H,27,28)(H,31,32)(H4,22,23,25,26,30)/t12-,15+/m1/s1
106400-81-1Relevant articles and documents
Synthesis of (6R)- And (6S)-5,10-dideazatetrahydrofolate oligo-γ-glutamates: Kinetics of multiple glutamate ligations catalyzed by folylpoly-γ-glutamate synthetase
Tomsho, John W.,McGuire, John J.,Coward, James K.
, p. 3388 - 3398 (2007/10/03)
Folylpoly-γ-glutamate synthetase (FPGS, EC 6.3.2.17) catalyzes the ATP-dependent ligation of glutamic acid to reduced folates including (6S)-5,6,7,8-tetrahydrofolate (H4PteGlu), as well as to anticancer drugs such as 5,10-dideaza-5,6,7,8-tetrahydrofolate ((6R)-DDAH 4PteGlu1, (6R)-DDATHF, Lometrexol(tm)). Synthesis of unlabeled mono- and polyglutamates, DDAH4PteGlu n (6R, n = 1-6; 6S, n = 1-2), as well as (6R)-DDAH 4Pte[14C]Glu1, was effected from (6R)- or (6S)-5,10-dideazatetrahydropteroyl azide and glutamic acid, H-Glu-γ- Glun-y-Glu-OH (n = 0-4), or [14C]glutamic acid, respectively. These compounds were evaluated as FPGS substrates to determine steady-state kinetic constants. Michaelis-Menten kinetics were observed for (6-R)-DDAH4PteGlu1, the isomer corresponding to H 4PteGlu, whereas marked substrate inhibition was observed for (6S)-DDAH4PteGlun (n = 1-2) and (6R)-DDAH 4PteGlun (n = 2-5), but not (6.R)-DDAH 4PteGlu6. Multiple ligation of glutamate renders a quantitative analysis of these data difficult. However, approximate values of KM = 0.65-1.6 μM and K1, = 144-417 μM for DDAH 4PteGln were obtained using a simple kinetic model. The Royal Society of Chemistry 2005.
Enantioselective synthesis of antifolates
-
, (2008/06/13)
A process and intermediates for the enantioselective synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid are disclosed.
Synthesis and Antifolate Activity of 5-Methyl-5,10-dideaza Analogues of Aminopterin and Folic Acid and an Alternative Synthesis of 5,10-Dideazatetrahydrofolic Acid, a Potent Inhibitor of Glycinamide Ribonucleotide Formyltransferase
Piper, J. R.,McCaleb, G. S.,Montgomery, J. A.,Kisliuk, R. L.,Gaumont, Y.,et al.
, p. 2164 - 2169 (2007/10/02)
The title compounds were prepared in extensions of a general synthetic approach used earlier to prepare 5-alkyl-5-deaza analogues of classical antifolates.Wittig condensation of 2,4-diaminopyridopyrimidine-6-carboxaldehyde (2a) and its 5-methyl ana