Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMDEA85)

• Drug Name: Trimetrexate Drug Info
• Synonyms: TMQ; Trimetrexato; Trimetrexatum; JB 11; Jb-11; Trimetrexato [INN-Spanish]; Trimetrexatum [INN-Latin]; Trimetrexate (USAN/INN); Trimetrexate [USAN:BAN:INN]; 2,4-Diamino-5-methyl-6-((3,4,5-trimethoxyanilino)methyl)quinazoline; 5-Methyl-6-(((3,4,5-trimethoxyphenyl)amino)methyl)-2,4-quinazolinediamine; 5-methyl-6-({[3,4,5-tris(methyloxy)phenyl]amino}methyl)quinazoline-2,4-diamine; 5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline-2,4-diamine; 6-[((3,4,5-Trimethoxyphenyl)amino)methyl]-5-methyl-2,4-quinazolinediamine

Indication

Disease Entry	ICD 11	Status	REF
Toxoplasmosis	1F57	Approved	[1]

• Therapeutic Class: Antifungal Agents
• Cross-matching ID:
  PubChem CID: 5583
  ChEBI ID: CHEBI:9737
  CAS Number: CAS 52128-35-5
  TTD Drug ID: DMDEA85
  VARIDT Drug ID: DR01434

Molecule-Related Drug Atlas

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[6]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[7]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[9]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[10]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[11]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[10]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[12]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[13]

Drug(s) Targeting Polypeptide deformylase (PDF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[14]
Meprobamate	DMHM93Y	Anxiety disorder	6B00-6B0Z	Approved	[15]
Pralatrexate	DMAO80I	Breast cancer	2C60-2C65	Approved	[16]
Ustekinumab	DMHTYK3	Plaque psoriasis	EA90.0	Approved	[17]
MCB-3837	DM0R4Z5	Malaria	1F40-1F45	Approved	[15]
Chlorproguanil	DM1IFGT	Malaria	1F40-1F45	Approved	[15]
LY333531	DMGMC8H	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
Metoprine	DM5GQD7	Advanced cancer	2A00-2F9Z	Phase 2	[19]
Aminopterin	DMQ9RBV	leukaemia	2A60-2B33	Withdrawn from market	[20]
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[2] , [3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
• [3] Synthesis and biological activities of tricyclic conformationally restricted tetrahydropyrido annulated furo[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases. J Med Chem. 1998 Apr 23;41(9):1409-16.
• [4] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [5] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [6] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [7] 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.
• [8] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [9] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [10] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [11] 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.
• [12] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [13] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [14] Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6.
• [15] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [16] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [17] Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother. 2002 Nov;46(11):3362-9.
• [18] Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. J Mol Biol. 2000 Jan 14;295(2):307-23.
• [19] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [20] 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.
• [21] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.