Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVC37M)

• DTT Name: Folate receptor alpha (FOLR1)
• Synonyms: Ovarian tumorassociated antigen MOv18; KB cells FBP; Folate receptor, adult; Folate receptor 1; FRalpha; FOLR1; Adult folatebinding protein
• Gene Name: FOLR1
• DTT Type: Successful target; [1]
• BioChemical Class: Folate receptor
• UniProt ID: FOLR1_HUMAN
• TTD ID: T83386
• Sequence:
  MAQRMTTQLLLLLVWVAVVGEAQTRIAWARTELLNVCMNAKHHKEKPGPEDKLHEQCRPW
  RKNACCSTNTSQEAHKDVSYLYRFNWNHCGEMAPACKRHFIQDTCLYECSPNLGPWIQQV
  DQSWRKERVLNVPLCKEDCEQWWEDCRTSYTCKSNWHKGWNWTSGFNKCAVGAACQPFHF
  YFPTPTVLCNEIWTHSYKVSNYSRGSGRCIQMWFDPAQGNPNEEVARFYAAAMSGAGPWA
  AWPFLLSLALMLLWLLS
• Function: Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pHafter receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release. Required for normal embryonic development and normal cell proliferation.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  Cargo concentration in the ER (R-HSA-5694530)
  COPII (Coat Protein 2) Mediated Vesicle Transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mirvetuximab soravtansine	DM5S4LX	Ovarian cancer	2C73	Approved	[2]
Pyrimethamine	DM5X7VY	Malaria	1F40-1F45	Approved	[1]

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
EC20	DMLA1ER	Ovarian cancer	2C73	Phase 3	[3]
Farletuzumab	DMFLWX1	Non-small-cell lung cancer	2C25.Y	Phase 3	[4]
MK-8109	DM84LO5	Ovarian cancer	2C73	Phase 3	[5]
EC-145	DM0KVJC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
FolateImmune	DMB9ADM	Renal cell carcinoma	2C90	Phase 2	[7]
BMS-753493	DMDQO0S	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]
Talotrexin	DM1AB4L	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[9]
EC0489	DM8RD4T	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
IMGN-853	DMR8OG2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
STRO-002	DMC5HXI	Ovarian cancer	2C73	Phase 1	[12]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Renal cancer	2C82	Kidney	1.85E-04	-1.41	-1.75
Ovarian cancer	2C82	Ovarian tissue	2.99E-04	1.81	2.81

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] EP patent application no. 2822386, Folate receptor alpha binding ligands.
• [4] Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer.Gynecol Oncol.2013 Jun;129(3):452-8.
• [5] 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.
• [6] 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.
• [7] Responsiveness of the Effective Consumer Scale (EC-17). J Rheumatol. 2009 Sep;36(9):2087-91.
• [8] 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.
• [9] Cancer chemotherapy: targeting folic acid synthesis. Cancer Manag Res. 2010; 2: 293-301.
• [10] National Cancer Institute Drug Dictionary (drug id 638649).
• [11] Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem. 2010 Jan;21(1):84-92.
• [12] Clinical pipeline report, company report or official report of Sutro Biopharma.