Drug Information

Drug (ID: DG00592) and It's Reported Resistant Information

• Name: Riluzole
• Synonyms: Riluzole; 1744-22-5; Rilutek; 2-Amino-6-(trifluoromethoxy)benzothiazole; 6-(trifluoromethoxy)benzo[d]thiazol-2-amine; 6-(trifluoromethoxy)-1,3-benzothiazol-2-amine; RP-54274; 2-amino-6-trifluoromethoxybenzothiazole; 2-amino-6-(trifluoromethoxy)benzo[d]thiazole; 2-Benzothiazolamine, 6-(trifluoromethoxy)-; PK-26124; RP 54274; C8H5F3N2OS; UNII-7LJ087RS6F; Riluzole (Rilutek); Amino-2 trifluoromethoxy-6 benzothiazole; MLS000069369; 6-Trifluoromethoxy-benzothiazol-2-ylamine; 2-Benzothiazolamine,6-(trifluoromethoxy)-; 2-Amino-6-(trifluoromethoxy)-benzothiazole; CHEMBL744; SMR000058231; 7LJ087RS6F; CHEBI:8863; Riluzol; 2-amino-6-(trifluoromethoxy)-1,3-benzothiazole; BENZOTHIAZOLE, 2-AMINO-6-TRIFLUOROMETHOXY-; MFCD00210213; NSC-753433; NSC-759823; NCGC00015882-09; Riluzolum; Riluzol [INN-Spanish]; Riluzolum [INN-Latin]; DSSTox_CID_25192; DSSTox_RID_80739; DSSTox_GSID_45192; Rilutek (TN); CAS-1744-22-5; Amino-2 trifluoromethoxy-6 benzothiazole [French]; Tiglutik; 2-amino-6-(trifluoromethoxyl)benzothiazole; Riluzole, solid; Riluzole [USAN:USP:INN:BAN]; Riluzole- Bio-X; BF-37; ALBB-006046; Prestwick-03A08; 6-(trifluoromethoxy)-2-benzothiazolamine; Tocris-0768; PK 26124; 6-trifluoromethoxybenzothiazole-2-yl-amine; Opera_ID_548; Lopac-R-116; Riluzole-13C-15N2; Prestwick0_000167; Prestwick1_000167; Prestwick2_000167; Prestwick3_000167; Spectrum2_000550; Biomol-NT_000245; cid_5070; Riluzole (JAN/USP/INN); Lopac0_001064; SCHEMBL78905; BSPBio_000033; BIDD:GT0055; SPBio_000599; SPBio_001954; BPBio1_000037; BPBio1_000837; GTPL2326; ZINC6481; DTXSID3045192; BDBM30705; Bio1_000416; Bio1_000905; Bio1_001394; HMS1773G08; HMS2089O19; HMS2094G07; HMS2233E14; HMS3263E10; HMS3371A09; HMS3657E13; Pharmakon1600-01505348; AMY14166; BCP02142; BHV-0223; HY-B0211; Riluzole - CAS 1744-22-5; Tiglutik (thickened oral suspension); Tox21_110252; Tox21_501064; AC-730; BBL013272; CCG-39528; NSC753433; NSC759823; s1614; STK503686; AKOS000265071; Tox21_110252_1; DB00740; KS-5231; LP01064; MCULE-9362288181; NSC 753433; NSC 759823; SDCCGSBI-0051034.P003; 2-amino-6-trifluoromethoxy-benzothiazole; 6-(trifluoromethoxy)benzothiazol-2-amine; 6-trifluoromethoxy-2-amino-benzothiazole; NCGC00015882-01; NCGC00015882-02; NCGC00015882-03; NCGC00015882-04; NCGC00015882-05; NCGC00015882-06; NCGC00015882-07; NCGC00015882-08; NCGC00015882-10; NCGC00015882-11; NCGC00015882-12; NCGC00015882-13; NCGC00015882-15; NCGC00015882-28; NCGC00023141-02; NCGC00023141-04; NCGC00023141-05; NCGC00023141-06; NCGC00261749-01; 6-(trifluoromethoxy)-2-aminobenzothiazole; 6-trifluoromethoxybenzo[d]thiazol-2-amine; BR164340; H090; SBI-0051034.P002; 2-Amino-6-(Trifluoromethoxy) Benzothiazole; 6-(Trifluoromethoxy)-2-amino-benzothiazole; DB-030335; EU-0101064; FT-0611194; R1174; SW196805-4; EN300-23782; 6-trifluoromethoxy-1,3-benzothiazol-2-ylamine; C07937; D00775; J10184; J10441; VU0239571-11; 744R225; Q415744; SR-01000002997-3; BRD-K21283037-001-02-5; BRD-K21283037-003-03-9; BRD-K21283037-003-06-2; F3282-0020; Z166605314; Rilutek; ; ; Rilutor; ; ; 6-(Trifluoromethoxy)-2-benzothiazolamine; Riluzole, United States Pharmacopeia (USP) Reference Standard; 2-Amino-6-(trifluoromethoxy)-1,3-benzothiazole;2-AMINO-6-(TRIFLUOROMETHOXY)BENZOTHIAZOLE
• Indication:
  In total 1 Indication(s)
  Amyotrophic lateral sclerosis [ICD-11: 8B60]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Spinal cord injury [ICD-11: 8C21]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Amyotrophic lateral sclerosis [ICD-11: 8B60]; [1]
• Target: Voltage-gated sodium channel alpha Nav1.9 (SCN11A); SCNBA_HUMAN; [2]
• Formula: C8H5F3N2OS
• IsoSMILES: C1=CC2=C(C=C1OC(F)(F)F)SC(=N2)N
• InChI: 1S/C8H5F3N2OS/c9-8(10,11)14-4-1-2-5-6(3-4)15-7(12)13-5/h1-3H,(H2,12,13)
• InChIKey: FTALBRSUTCGOEG-UHFFFAOYSA-N
• PubChem CID: 5070
• ChEBI ID: CHEBI:8863
• TTD Drug ID: D0H0KB
• VARIDT ID: DR00205
• INTEDE ID: DR1425
• DrugBank ID: DB00740

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-08: Nervous system diseases

Amyotrophic lateral sclerosis [ICD-11: 8B60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Amyotrophic lateral sclerosis [ICD-11: 8B60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: bEND.3 cells; Brain; Homo sapiens (Human); CVCL_0170
• In Vitro Model: C8D1A cells; Colon; Mus musculus (Mouse); CVCL_6379
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: High-performance liquid chromatography
• Mechanism Description: Riluzole is moderately effective for ALS patients and prolongs survival by only three months. According to previous studies, increased P-gp transporter activity and expression are induced by ALS. As riluzole is a substrate of P-gp, the inductions potentially limit the brain distribution of riluzole and further promote drug resistance in the later stage of ALS disease.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Amyotrophic lateral sclerosis [ICD-11: 8B60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: bEND.3 cells; Brain; Homo sapiens (Human); CVCL_0170
• In Vitro Model: C8D1A cells; Colon; Mus musculus (Mouse); CVCL_6379
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: High-performance liquid chromatography
• Mechanism Description: BEND.3 Cells were treated with riluzole and verapamil liposomes at different doses and time durations to determine the inhibitory levels of P-gp. In the buffer control treatment, the expression of P-gp was noted as a baseline level (100%). After the exposure to 5, 10, 20, 30, and 40 ug/ml cocktail liposomes for 48 h, bEND.3 cells resulted in a distinct decrease of P-gp expression with 93.0 plus or minus 5.2%, 85.8 plus or minus 4.7%, 50.3 plus or minus 5.6% 26.2 plus or minus 5.1%, and 20.8 plus or minus 4.9% of the baseline level, respectively. The extent of the decrease was linearly dependent on the concentration of verapamil in formulations (5 to 30 ug/ml), while inhibited levels of P-gp by 30 ug/ml and 40 ug/ml of verapamil cocktail liposome were not significantly different.

Spinal cord injury [ICD-11: 8C21]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Spinal cord injury [ICD-11: 8C21.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Abcb1a Knockout rats model; Mus musculus
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: High performance liquid chromatography assay
• Mechanism Description: Riluzole spinal cord disposition was significantly higher in knockout rats than in WT rats at 10 days post-spinal cord injury (p=0.019), confirming that Pgp plays a critical role in diminishing spinal cord riluzole disposition following spinal cord injury.

References

• Ref 1: Verapamil and riluzole cocktail liposomes overcome pharmacoresistance by inhibiting P-glycoprotein in brain endothelial and astrocyte cells: A potent approach to treat amyotrophic lateral sclerosis .Eur J Pharm Sci. 2018 Jul 30;120:30-39. doi: 10.1016/j.ejps.2018.04.026. Epub 2018 Apr 26. 10.1016/j.ejps.2018.04.026
• Ref 2: The dual cyclooxygenase/5-lipoxygenase inhibitor licofelone attenuates p-glycoprotein-mediated drug resistance in the injured spinal cord .J Neurotrauma. 2013 Feb 1;30(3):211-26. doi: 10.1089/neu.2012.2587. Epub 2013 Jan 23. 10.1089/neu.2012.2587