WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206596
CAS#: 152946-68-4 (HCl salt)
Description: Nolatrexed, also known as AG337, is a thymidylate synthase inhibitor with potential anticancer activity. A phase II study of nolatrexed in 2007 in advanced HCC patients demonstrated minimal activity and significant stomatitis. Hence, it does not warrant further study as a single agent for this disease.
MedKoo Cat#: 206596
Name: Nolatrexed HCl
CAS#: 152946-68-4 (HCl salt)
Chemical Formula: C14H14Cl2N4OS
Exact Mass: 356.0265
Molecular Weight: 357.25
Elemental Analysis: C, 47.07; H, 3.95; Cl, 19.85; N, 15.68; O, 4.48; S, 8.97
Related CAS #: 152946-68-4 (HCl salt); 147149-76-6 (free base)
Synonym: AG337; AG 337; AG-337; Nolatrexed HCl; Nolatrexed dihydrochloride; brand name: Thymitaq.
IUPAC/Chemical Name: 2-Amino-6-methyl-5-(4-pyridylthio)-1H-quinazolin-4-one dihydrochloride
InChi Key: PJKVJJYMWOCLIJ-UHFFFAOYSA-N
InChi Code: InChI=1S/C14H12N4OS.2ClH/c1-8-2-3-10-11(13(19)18-14(15)17-10)12(8)20-9-4-6-16-7-5-9;;/h2-7H,1H3,(H3,15,17,18,19);2*1H
SMILES Code: O=C1N=C(N)NC2=C1C(SC3=CC=NC=C3)=C(C)C=C2.[H]Cl.[H]Cl
1: Zheng J, Lin J, Wang L, Zhou J, Xie B, Xu T, Zhang W. Metastatic nasopharyngeal carcinoma outcomes in patients on cisplatin with nolatrexed or 5-fluorouracil. Oncol Res Treat. 2014;37(10):540-4. doi: 10.1159/000368107. Epub 2014 Sep 16. PubMed PMID: 25342504.
2: Tian SB, Jing CQ, Li LP. [Effects of RNA interference and nolatrexed on thymidylate synthase expression and cell proliferation of human colorectal carcinoma LOVO cells]. Zhonghua Wei Chang Wai Ke Za Zhi. 2012 Nov;15(11):1187-91. Chinese. PubMed PMID: 23172536.
3: Wang GF, Zhang JY, Wu SY, Xu W, Wan SH, Shao CF, Zhang JJ. [Measurement of plasma concentration and bioavailability of nolatrexed dihydrochloride in mice]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Nov;28(11):1993-5. Chinese. PubMed PMID: 19033111.
4: Chen SZ, Wang SM, Zhang JR. [Preparation of long-circulating nolatrexed dihydrochloride liposomes and its antitumor activity]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Mar;28(3):403-5. Chinese. PubMed PMID: 18359701.
5: Gish RG, Porta C, Lazar L, Ruff P, Feld R, Croitoru A, Feun L, Jeziorski K, Leighton J, Gallo J, Kennealey GT. Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin. J Clin Oncol. 2007 Jul 20;25(21):3069-75. PubMed PMID: 17634485.
6: Jhawer M, Rosen L, Dancey J, Hochster H, Hamburg S, Tempero M, Clendeninn N, Mani S. Phase II trial of nolatrexed dihydrochloride [Thymitaq, AG 337] in patients with advanced hepatocellular carcinoma. Invest New Drugs. 2007 Feb;25(1):85-94. Epub 2006 Sep 7. PubMed PMID: 16957834.
7: Li YL, Wu SG. [Effects of nolatrexed on thymidylate synthase protein expression]. Di Yi Jun Yi Da Xue Xue Bao. 2004 Aug;24(8):881-4. Chinese. PubMed PMID: 15321751.
8: Pivot X, Wadler S, Kelly C, Ruxer R, Tortochaux J, Stern J, Belpomme D, Humblet Y, Domenge C, Clendeninn N, Johnston A, Penning C, Schneider M. Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer. Ann Oncol. 2001 Nov;12(11):1595-9. PubMed PMID: 11822760.
9: Estlin EJ, Pinkerton CR, Lewis IJ, Lashford L, McDowell H, Morland B, Kohler J, Newell DR, Boddy AV, Taylor GA, Price L, Ablett S, Hobson R, Pitsiladis M, Brampton M, Clendeninn N, Johnston A, Pearson AD. A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children's Cancer Study Group Investigation. Br J Cancer. 2001 Jan 5;84(1):11-8. PubMed PMID: 11139306; PubMed Central PMCID: PMC2363615.
10: Hughes AN, Griffin MJ, Newell DR, Calvert AH, Johnston A, Kerr B, Lee C, Liang B, Boddy AV. Clinical pharmacokinetic and in vitro combination studies of nolatrexed dihydrochloride (AG337, Thymitaq) and paclitaxel. Br J Cancer. 2000 May;82(9):1519-27. PubMed PMID: 10789718; PubMed Central PMCID: PMC2363406.
11: Mok TS, Leung TW, Lee SD, Chao Y, Chan AT, Huang A, Lui MC, Yeo W, Chak K, Johnston A, Johnson P. A multi-centre randomized phase II study of nolatrexed versus doxorubicin in treatment of Chinese patients with advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 1999;44(4):307-11. PubMed PMID: 10447578.
12: Stuart K, Tessitore J, Rudy J, Clendennin N, Johnston A. A Phase II trial of nolatrexed dihydrochloride in patients with advanced hepatocellular carcinoma. Cancer. 1999 Aug 1;86(3):410-4. PubMed PMID: 10430248.
13: Jodrell DI, Bowman A, Rye R, Byrne B, Boddy A, Rafi I, Taylor GA, Johnston A, Clendeninn NJ. A phase I study of the lipophilic thymidylate synthase inhibitor Thymitaq (nolatrexed dihydrochloride) given by 10-day oral administration. Br J Cancer. 1999 Feb;79(5-6):915-20. PubMed PMID: 10070890; PubMed Central PMCID: PMC2362691.
14: Hughes AN, Rafi I, Griffin MJ, Calvert AH, Newell DR, Calvete JA, Johnston A, Clendeninn N, Boddy AV. Phase I studies with the nonclassical antifolate nolatrexed dihydrochloride (AG337, THYMITAQ) administered orally for 5 days. Clin Cancer Res. 1999 Jan;5(1):111-8. PubMed PMID: 9918208.
15: Rafi I, Boddy AV, Calvete JA, Taylor GA, Newell DR, Bailey NP, Lind MJ, Green M, Hines J, Johnstone A, Clendeninn N, Calvert AH. Preclinical and phase I clinical studies with the nonclassical antifolate thymidylate synthase inhibitor nolatrexed dihydrochloride given by prolonged administration in patients with solid tumors. J Clin Oncol. 1998 Mar;16(3):1131-41. PubMed PMID: 9508200.
