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

General Information of Drug (ID: DM1AB4L)

• Drug Name: Talotrexin Drug Info
• Synonyms: Talvesta; Talotrexin ammonium; PT-523; PT-633; 10-deaza-PT-523

Indication

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

• Cross-matching ID:
  PubChem CID: 130731
  CAS Number: CAS 113857-87-7
  TTD Drug ID: DM1AB4L
  VARIDT Drug ID: DR00882

Molecule-Related Drug Atlas

Drug(s) Targeting Folate receptor alpha (FOLR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pyrimethamine	DM5X7VY	Malaria	1F40-1F45	Approved	[4]
Mirvetuximab soravtansine	DM5S4LX	Ovarian cancer	2C73	Approved	[5]
EC20	DMLA1ER	Ovarian cancer	2C73	Phase 3	[6]
MK-8109	DM84LO5	Ovarian cancer	2C73	Phase 3	[7]
Farletuzumab	DMFLWX1	Non-small-cell lung cancer	2C25.Y	Phase 3	[8]
EC-145	DM0KVJC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
FolateImmune	DMB9ADM	Renal cell carcinoma	2C90	Phase 2	[10]
BMS-753493	DMDQO0S	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[11]
EC0489	DM8RD4T	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
IMGN-853	DMR8OG2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]

Drug(s) Affected By Reduced folate transporter (SLC19A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[14]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[3]
Pemetrexed	DMMX2E6	Central nervous system lymphoma	2B33.5	Approved	[3]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Selenium	DM25CGV	N. A.	N. A.	Approved	[16]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[18]
Atenolol	DMNKG1Z	Angina pectoris	BA40	Approved	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Folate receptor alpha (FOLR1)	TTVC37M	FOLR1_HUMAN	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Reduced folate transporter (SLC19A1)	OTWB0BTO	S19A1_HUMAN	Drug Response	[3]

References

• [1] ClinicalTrials.gov (NCT00112060) A Study to Assess the Safety and Preliminary Efficacy of PT-523 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC). U.S. National Institutes of Health.
• [2] Cancer chemotherapy: targeting folic acid synthesis. Cancer Manag Res. 2010; 2: 293-301.
• [3] The inverse relationship between reduced folate carrier function and pemetrexed activity in a human colon cancer cell line. Mol Cancer Ther. 2006 Feb;5(2):438-49. doi: 10.1158/1535-7163.MCT-05-0243.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] EP patent application no. 2822386, Folate receptor alpha binding ligands.
• [7] A current review of folate receptor alpha as a potential tumor target in non-small-cell lung cancer. Drug Des Devel Ther. 2015; 9: 4989-4996.
• [8] Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer.Gynecol Oncol.2013 Jun;129(3):452-8.
• [9] Significance of Folate Receptor alpha and Thymidylate Synthase Protein Expression in Patients with Non-Small Cell Lung Cancer treated with Pemetrexed. J Thorac Oncol. 2013 January; 8(1): 19-30.
• [10] Responsiveness of the Effective Consumer Scale (EC-17). J Rheumatol. 2009 Sep;36(9):2087-91.
• [11] A phase I pharmacokinetic and safety analysis of epothilone folate (BMS-753493), a folate receptor targeted chemotherapeutic agent in humans with advanced solid tumors. Invest New Drugs. 2015 Apr;33(2):321-31.
• [12] National Cancer Institute Drug Dictionary (drug id 638649).
• [13] Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem. 2010 Jan;21(1):84-92.
• [14] The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivationRFC as a double edged sword in folate homeostasis. J Biol Chem. 2008 Jul 25;283(30):20687-95.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [18] Folic acid uptake by the human syncytiotrophoblast: interference by pharmacotherapy, drugs of abuse and pathological conditions. Reprod Toxicol. 2009 Dec;28(4):511-20. doi: 10.1016/j.reprotox.2009.07.001. Epub 2009 Jul 16.
• [19] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.