Details of the Drug

General Information of Drug (ID: DMOF0CA)

Drug Name

Nolatrexed

Synonyms

Thymitaq; AG-337; ZX-337; Nolatrexed (intravenous), EXIMIAS

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

284.34

Topological Polar Surface Area (xlogp)

1.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

Chemical Identifiers

Formula: C14H12N4OS
IUPAC Name: 2-amino-6-methyl-5-pyridin-4-ylsulfanyl-3H-quinazolin-4-one
Canonical SMILES: CC1=C(C2=C(C=C1)N=C(NC2=O)N)SC3=CC=NC=C3
InChI: InChI=1S/C14H12N4OS/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)
InChIKey: XHWRWCSCBDLOLM-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 135400184
CAS Number: 147149-76-6
DrugBank ID: DB12912
TTD ID: D06WQT
VARIDT ID: DR01461

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Candida Thymidylate synthase (Candi TMP1)	TTU6BFZ	TYSY_CANAL	Inhibitor	[2]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[3]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	ClinicalTrials.gov (NCT00012324) Nolatrexed Dihydrochloride Compared With Doxorubicin in Treating Patients With Recurrent or Unresectable Liver Cancer. U.S. National Institutes of Health.
2	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.
3	Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
4	Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
5	Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
6	The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
7	Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
8	Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
9	Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
10	The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
11	Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
12	Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
13	The efficacy of the combination therapy of 5-fluorouracil, cisplatin and leucovorin for hepatocellular carcinoma and its predictable factors. Cancer Chemother Pharmacol. 2004 Apr;53(4):296-304.
14	Loss of folylpoly-gamma-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int J Cancer. 2003 Feb 20;103(5):587-99.
15	Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40.
16	Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
17	UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.
18	DNA damage and homologous recombination signaling induced by thymidylate deprivation. Biochem Pharmacol. 2008 Oct 15;76(8):987-96.
19	Antisense down-regulation of thymidylate synthase to suppress growth and enhance cytotoxicity of 5-FUdR, 5-FU and Tomudex in HeLa cells. Br J Pharmacol. 1999 Aug;127(8):1777-86.
20	Decreased levels of UMP kinase as a mechanism of fluoropyrimidine resistance. Mol Cancer Ther. 2009 May;8(5):1037-44.
21	Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9.
22	Cooperative inhibition of human thymidylate synthase by mixtures of active site binding and allosteric inhibitors. Biochemistry. 2007 Mar 13;46(10):2823-30.