Methotrexate α-tert-butyl ester

Names

[ Name ]:
Methotrexate α-tert-butyl ester

[Synonym ]:
(S)-2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-pentanedioic acid 1-tert-butyl ester
methotrexate-α-tert-butylester
methotrexate-α-OtBu
methotrexate
methotrexate α-tert-butyl ester
α-tert-butyl-N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamate
MTX-α-OtBu

Biological Activity

[Description]:

Methotrexate α-tert-butyl ester, capped by OtBu, significantly reduces tumor growth in HT1080 tumor bearing mice. Methotrexate is an antimetabolite and antifolate agent and is also an immunosuppressant and antineoplastic agent[1][2][3][4].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Antifolate

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

[In Vitro]

OtBu-MTX-PVG is less HT1080 than MTX-PVG against HT1080 cells. It shows that protection of the α-carboxyl group of MTX results in reduced in vitro activity[1].

[In Vivo]

Lys-MTXcleavable- (OtBu) significantly reduces tumor growth in HT1080 tumor bearing mice[1]. The protection of the α-carboxyl group of methotrexate may be used to improve the circulatory half-life and reduce the liver accumulation of similar MTX-conjugated dendrimers, while still retaining antitumor activity in vivo[1]. Animal Model: Female, Balb/c nu/nu, 6 weeks (bearing HT1080 cells)[1] Dosage: 30 mg/kg Administration: Once per week for 2 weeks Result: Showed a significant (63%) reduction in tumor size on day 12.

[References]

[1]. Kaminskas LM, et al. Capping methotrexate α-carboxyl groups enhances systemic exposure and retains the cytotoxicity of drug conjugated PEGylated polylysine dendrimers. Mol Pharm. 2011;8(2):338-349.

[2]. Tian H, et al. Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis. Bull NYU Hosp Jt Dis. 2007;65(3):168-73.

[3]. Swierkot J, et al. Methotrexate in rheumatoid arthritis. Pharmacol Rep. 2006 Jul-Aug;58(4):473-92.

[4]. Ehab Tousson, et al. The Effect of L-carnitine on Amethopterin-induced Toxicity in Rat Large Intestine.

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₄H₃₀N₈O₅

[ Molecular Weight ]:
510.54600

[ Exact Mass ]:
510.23400

[ PSA ]:
199.54000

[ LogP ]:
3.07880

Related Compounds

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