Drug Information

Drug (ID: DG00722) and It's Reported Resistant Information

• Name: Eflornithine
• Synonyms: EFLORNITHINE; 70052-12-9; Ornidyl; 2-(Difluoromethyl)ornithine; dfmo; 2,5-diamino-2-(difluoromethyl)pentanoic acid; Difluoromethylornithine; Vaniqa; alpha-Difluoromethylornithine; 2-(Difluoromethyl)-DL-ornithine; Eflornithine free base; alpha-(Difluoromethyl)-DL-ornithine; Difluromethylornithine; RMI 71782; 67037-37-0; DL-.alpha.-Difluoromethylornithine; CHEMBL830; DFMO HCl; CHEBI:41948; 70052-12-9 (free base); NSC337250; Eflornithinum; Eflornitina; Eflornithinum [Latin]; Eflornitina [Spanish]; 2,5-diamino-2-(difluoromethyl)pentanoic acid.; .alpha.-DFMO HCl; DFMO (growth regulator); Eflornithine [INN:BAN]; 70050-56-5; L-DFMO;L-RMI71782;L-alpha-difluoromethylornithine; DL-alpha-(Difluoromethyl)ornithine; DL-Ornithine, monohydrochloride; MDL 71782; Eflornithine (INN); CCRIS 3295; Ornithine, 2-(difluoromethyl)-; NSC-337250; DL-Ornithine, 2-(difluoromethyl)-; (-)-2-Difluoromethylornithine; BRN 2250529; alpha,delta-Diamino-alpha-(difluoromethyl)valeric acid; SR-01000076229; C6H12F2N2O2; HSDB 7923; alpha-DFMO; (RS)-eflornithine; RFI 7178; Lopac0_000429; SCHEMBL26327; GTPL5176; 2-(difluoromethyl)-L-ornithine; alpha-difluoromethyl-dl-ornithine; DTXSID3020467; H-DL-(a-Difluoromethyl)Orn-OH; BCP10516; HY-B0744; 2-(difluoromethyl)ornithine (DMFO); BDBM50028197; HSCI1_000267; MFCD00221766; AKOS006281180; CCG-204521; DB06243; SDCCGSBI-0050414.P002; NCGC00015316-02; NCGC00015316-03; NCGC00015316-06; NCGC00015316-15; NCGC00162152-01; K100; 2-difluoromethyl-2,5-diaminopentanoic acid; DB-055371; FT-0630795; FT-0720946; FT-0775156; 2-(difluoromethyl)-2,5-diaminopentanoic acid;; C07997; D07883; 020E916; A936641; Q424751; (RS)-2,5-diamino-2-(difluoromethyl)pentanoic acid; DFMO;MDL71782;RMI71782;; A-difluoromethylornithine; SR-01000076229-10
• Indication:
  In total 2 Indication(s)
  African trypanosomiasis [ICD-11: 1F51]; Approved; [1]
  Trypanosomiasis [ICD-11: 1D51-1F53]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  African trypanosomiasis [ICD-11: 1F51]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Osteosarcoma [ICD-11: 2B51]; [2]
• Formula: C6H12F2N2O2
• IsoSMILES: C(CC(C(F)F)(C(=O)O)N)CN
• InChI: 1S/C6H12F2N2O2/c7-4(8)6(10,5(11)12)2-1-3-9/h4H,1-3,9-10H2,(H,11,12)
• InChIKey: VLCYCQAOQCDTCN-UHFFFAOYSA-N
• PubChem CID: 3009
• TTD Drug ID: D05UOW
• VARIDT ID: DR00843
• DrugBank ID: DB06243

Type(s) of Resistant Mechanism of This Drug

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Osteosarcoma [ICD-11: 2B51]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Yes-associated protein 1 (YAP1) [2]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: 6-8-week-old female nude mice, with osteosarcoma cells; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: DFMO treatment curbs the phosphorylation of YAP1 protein in OS cells, promoting nuclear entry and initiating the YAP1-mediated glutamine metabolic pathway. This reduces intracellular ROS levels, countering DFMO's anticancer effect. The therapeutic efficacy of DFMO can be amplified both in vivo and in vitro by combining it with the YAP1 inhibitor CIL56 or the glutaminase inhibitor CB-839.

References

• Ref 1: Drug resistance in human African trypanosomiasis .Future Microbiol. 2011 Sep;6(9):1037-47. doi: 10.2217/fmb.11.88. 10.2217/fmb.11.88
• Ref 2: Disrupting YAP1-mediated glutamine metabolism induces synthetic lethality alongside ODC1 inhibition in osteosarcoma. Cell Oncol (Dordr). 2024 Oct;47(5):1845-1861.