Drug Information

Drug (ID: DG02017) and It's Reported Resistant Information

• Name: Anlotinib
• Synonyms: Anlotinib|1058156-90-3|catequentinib|AL3818|AL-3818|UNII-GKF8S4C432|GKF8S4C432|1-[[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinolin-7-yl]oxymethyl]cyclopropan-1-amine|CATEQUENTINIB [INN]|AL 3818|CATEQUENTINIB [WHO-DD]|1-(((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropan-1-amine|1-((4-(4-fluoro-2-methyl-1h-indol-5-yloxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropan-amine|1-[({4-[(4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY]-6-METHOXYQUINOLIN-7-YL}OXY)METHYL]CYCLOPROPAN-1-AMINE|Cyclopropanamine, 1-(((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-quinolinyl)oxy)methyl)-|Anlotinib?|1-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinolin-7-yl)oxymethyl)cyclopropan-1-amine|Cyclopropanamine, 1-[[[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-quinolinyl]oxy]methyl]-|Catequentinib (USAN/INN)|CATEQUENTINIB [USAN]|GTPL9601|SCHEMBL2063386|CHEMBL4303201|KSMZEXLVHXZPEF-UHFFFAOYSA-N|GLXC-10628|BCP24991|EX-A2427|ISB15690|NSC832523|AKOS030526233|CS-5396|DB11885|NSC-832523|SB19798|HY-19716|4678B|NS00073391|C13643|D12526|BRD-K36949735-001-01-1|Q27279141|1-(((4-((4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY)-6-METHOXY-7-QUINOLINYL)OXY)METHYL)CYCLOPROPANAMINE
• Indication:
  In total 1 Indication(s)
  Synovial sarcoma [ICD-11: 2B5A]; Phase 3
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Oral squamous cell carcinoma [ICD-11: 2B6E]; [1]
• Target: Proto-oncogene c-Src (SRC); SRC_HUMAN
• Formula: C23H22FN3O3
• IsoSMILES: CC1=CC2=C(N1)C=CC(=C2F)OC3=C4C=C(C(=CC4=NC=C3)OCC5(CC5)N)OC
• InChI: InChI=1S/C23H22FN3O3/c1-13-9-15-16(27-13)3-4-19(22(15)24)30-18-5-8-26-17-11-21(20(28-2)10-14(17)18)29-12-23(25)6-7-23/h3-5,8-11,27H,6-7,12,25H2,1-2H3
• InChIKey: KSMZEXLVHXZPEF-UHFFFAOYSA-N
• PubChem CID: 25017411
• TTD Drug ID: D0G2CG
• INTEDE ID: DR1881

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

Oral squamous cell carcinoma [ICD-11: 2B6E]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Methyltransferase like 1 (METTL1) [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Adding to this, our research shows that METTL1-modified m7G tRNA increases translation of enzymes associated with the respiratory chain, boosting OXPHOS capacity in anlotinib-resistant cells. This highlights the potential of epigenetic interventions in overcoming TKI resistance.

Key Molecule: Methyltransferase like 1 (METTL1) [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Adding to this, our research shows that METTL1-modified m8G tRNA increases translation of enzymes associated with the respiratory chain, boosting OXPHOS capacity in anlotinib-resistant cells. This highlights the potential of epigenetic interventions in overcoming TKI resistance.

References

• Ref 1: Metabolic reprogramming driven by METTL1-mediated tRNA m7G modification promotes acquired anlotinib resistance in oral squamous cell carcinoma. Transl Res. 2024 Jun;268:28-39.