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

General Information of Drug (ID: DM276N1)

• Drug Name: PIRITREXIM Drug Info
• Synonyms: Piritrexim; 72732-56-0; Piritrexim [INN]; Piritreximum [Latin]; Piritrexime [French]; 6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine; Piritrexima [Spanish]; BW 301U; UNII-MK2A783ZUT; BW-301U; TCMDC-137235; BRN 5768301; MK2A783ZUT; CHEMBL7492; 2,4-Diamino-5-methyl-6-(2,5-dimethoxybenzyl)pyrido(2,3-d)pyrimidine; 6-(2,5-DIMETHOXY-BENZYL)-5-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4-DIAMINE; 6-((2,5-Dimethoxyphenyl)methyl)-5-methylpyrido(2,3-d)pyrimidine-2,4-diamine

Indication

Disease Entry	ICD 11	Status	REF
Bladder cancer	2C94	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 54369
  CAS Number: CAS 72732-56-0
  TTD Drug ID: DM276N1
  VARIDT Drug ID: DR01377

Molecule-Related Drug Atlas

Drug(s) Targeting Dihydrofolate reductase (DHFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trimethoprim	DMM7CHK	Acute otitis media	AB00	Approved	[4]
Aminosalicylic Acid	DMENSL5	Crohn disease	DD70	Approved	[4]
Leucovorin Calcium	DMNWZJG	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Methotrexate Sodium	DM5XH2C	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Iclaprim	DM7YNV9	Bacterial infection	1A00-1C4Z	Phase 3	[6]
CH-4051	DMLQRYH	Rheumatoid arthritis	FA20	Phase 2	[7]
MDAM (y-methylene-10-deazaaminopterin)	DM1DISM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
L-MDAM	DMU901D	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
VYR 006	DMC9N7D	Toxoplasmosis	1F57	Phase 1	[10]
TNP-351	DMW05DS	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[11]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[14]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[15]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[16]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[17]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[18]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dihydrofolate reductase (DHFR)	TTYZVDJ	DYR_HUMAN	Modulator	[2]

Drug Transporter (DTP)

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

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7414).
• [2] Structural variations of piritrexim, a lipophilic inhibitor of human dihydrofolate reductase: synthesis, antitumor activity and molecular modeling ... Eur J Med Chem. 2004 Dec;39(12):1079-88.
• [3] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Biochemical factors in the selectivity of leucovorin rescue: selective inhibition of leucovorin reactivation of dihydrofolate reductase and leucovorin utilization in purine and pyrimidine biosynthesis by methotrexate and dihydrofolate polyglutamates.NCI Monogr.1987;(5):17-26.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] CH-1504, a metabolically inert antifolate for the potential treatment of rheumatoid arthritis. IDrugs. 2010 Aug;13(8):559-67.
• [8] Evaluation of the importance of hydrophobic interactions in drug binding to dihydrofolate reductase. J Med Chem. 1988 Jan;31(1):129-37.
• [9] Polyglutamylation of the dihydrofolate reductase inhibitor gamma-methylene-10-deazaaminopterin is not essential for antitumor activity. Clin Cancer Res. 1996 Apr;2(4):707-12.
• [10] Clinical pipeline report, company report or official report of Vyera Pharmaceuticals.
• [11] A Ring-Transformation/Ring-Annulation Strategy for the Synthesis of the DHFR Inhibitor, TNP-351: A Correction. J Org Chem. 1996 Nov 1;61(22):7973-7974.
• [12] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [13] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [14] 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.
• [15] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [16] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [17] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [18] 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.
• [19] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [20] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.