TALOTREXIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H27N9O6
Molecular Weight	573.56
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(N)=C2N=C(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCCNC(=O)C4=C(C=CC=C4)C(O)=O)C(O)=O)C=NC2=N1

InChI

InChIKey=NYQPLPNEESYGNO-IBGZPJMESA-N

InChI=1S/C27H27N9O6/c28-21-20-22(36-27(29)35-21)32-13-16(33-20)12-31-15-9-7-14(8-10-15)23(37)34-19(26(41)42)6-3-11-30-24(38)17-4-1-2-5-18(17)25(39)40/h1-2,4-5,7-10,13,19,31H,3,6,11-12H2,(H,30,38)(H,34,37)(H,39,40)(H,41,42)(H4,28,29,32,35,36)/t19-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.biospace.com/article/releases/hana-biosciences-inc-receives-orphan-drug-designation-for-talotrexin-pt-523-for-the-treatment-of-acute-lymphoblastic-leukemia-/ | https://clinicaltrials.gov/ct2/show/NCT00458744 | https://clinicaltrials.gov/ct2/show/NCT00112060

Talotrexin (also known as PT-523) was developed as a nonpolyglutamatable antifolate drug for the treatment of various types of tumors. It is known that antifolates are a class of cytotoxic or antineoplastic agents, which inhibit or prevent the maturation and proliferation of malignant cells. Talotrexin was studied in clinical trials for the treatment of brain and central nervous system tumors, leukemia, lymphoma, unspecified childhood solid tumor. However, this study was withdrawn because of toxicity. In addition, was studied in phase I/II multicenter clinical trial in patients with non-small-cell Lung carcinoma, this study was also withdrawn. The withdrawal was related to incidences of dose-limiting mucositis and myelosuppression. However, on May 22, 2006, was announced that the U.S. Food and Drug Administration has granted orphan drug designation for talotrexin in patients with acute lymphoblastic leukemia (ALL).

Originator

Approval Year

PubMed

Title	Date	PubMed
The inverse relationship between reduced folate carrier function and pemetrexed activity in a human colon cancer cell line.	2006 Feb	16505119
Treatment of acute lymphoblastic leukaemia : a new era.	2007	17927282
Emerging therapeutic options for Philadelphia-positive acute lymphocytic leukemia.	2007 Mar	17355221
Clinical potency of methotrexate, aminopterin, talotrexin and pemetrexed in childhood leukemias.	2010 May	19784838
Cancer chemotherapy: targeting folic acid synthesis.	2010 Nov 19	21301589

Sample Use Guides

In Vivo Use Guide

10 mg/m2 dose of PT523 administered day 1 of a 28-day cycle as a 5 minute IV infusion (IV bolus)

Route of Administration: Intravenous

Name

Type

Language

TALOTREXIN

Official Name

English

NSC-633713

Code

English

2-(((4S)-4-CARBOXY-4-((4-(((2,4-DIAMINOPTERIDIN-6-YL)METHYL)AMINO)BENZOYL)AMINO)BUTYL)CARBAMOYL)BENZOIC ACID

Systematic Name

English

talotrexin [INN]

Common Name

English

BENZOIC ACID,2-((((4S)-4-CARBOXY-4-((4-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)AMINO)BENZOYL)AMINO)BUTYL)AMINO)CARBONYL)-

Common Name

English

NSC-623017

Code

English

Talotrexin [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

221306