Drug Information

Drug (ID: DG01166) and It's Reported Resistant Information

• Name: Axitinib
• Synonyms: Axitinib; 319460-85-0; AG-013736; Inlyta; AG 013736; (E)-N-Methyl-2-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)benzamide; UNII-C9LVQ0YUXG; AG-13736; AG013736; C9LVQ0YUXG; N-methyl-2-((3-((1E)-2-(pyridin-2-yl)ethenyl)-1H-indazol-6-yl)sulfanyl)benzamide; CHEBI:66910; (E)-N-methyl-2-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-ylthio)benzamide; N-methyl-2-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]benzamide; MFCD09837898; NSC757441; N-methyl-2-({3-[(E)-2-(pyridin-2-yl)ethenyl]-1H-indazol-6-yl}sulfanyl)benzamide; NSC-757441; NCGC00241108-01; S1005; DSSTox_CID_28975; DSSTox_RID_83240; DSSTox_GSID_49049; Axitinib (AG 013736); C22H18N4OS; N-methyl-2-({3-[(E)-2-(pyridin-2-yl)vinyl]-1H-indazol-6-yl}sulfanyl)benzamide; CAS-319460-85-0; axitinibum; Axitinib [USAN:INN:JAN]; 4agc; Inlyta (TN); AG13736; 4ag8; Axitinib (JAN/USAN); AG-013736;Axitinib; Axitinib,AG-013736; MLS006010164; SCHEMBL172918; GTPL5659; Axitinib, >=98% (HPLC); CHEMBL1289926; DTXSID3049049; N-methyl-2-[[3-[2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]benzamide; SCHEMBL22930506; BDBM25117; CHEBI:94568; EX-A337; QCR-109; SYN1014; BCPP000372; AOB87786; BCP01371; ZINC3816287; Tox21_113597; NSC799341; AKOS015902898; Tox21_113597_1; AC-1539; BCP9000345; CCG-264772; CS-0116; DB06626; KS-1448; NSC 757441; NSC-799341; Benzamide, N-methyl-2-((3-((E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)-; NCGC00241108-04; NCGC00241108-06; HY-10065; SMR002530046; AM20090673; SW219464-1; D03218; AB01274739-01; AB01274739_02; 460A850; SR-01000941566; J-502064; Q-200662; Q4830631; SR-01000941566-1; BRD-K29905972-001-01-4; BRD-K29905972-001-02-2; Benzamide, N-methyl-2-((3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazo)-6-yl)thio)-; Benzamide, N-methyl-2-[[3-[(1E)-2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]-; N-Methyl-[[3[(1E)-2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]-benzamide; N-methyl-2-({3-[(E)-2-pyridin-2-ylethenyl]-2H-indazol-6-yl}sulfanyl)benzamide; N-METHYL-2-(3-((E)-2-PYRIDIN-2-YL-VINYL)-1H-INDAZOL-6-YLSULFANYL)-BENZAMIDE
• Indication:
  In total 1 Indication(s)
  Renal cell carcinoma [ICD-11: 2C90]; Approved; [1]
• Target: Vascular endothelial growth factor receptor 2 (KDR); VGFR2_HUMAN; [1]
• Formula: C22H18N4OS
• IsoSMILES: CNC(=O)C1=CC=CC=C1SC2=CC3=C(C=C2)C(=NN3)/C=C/C4=CC=CC=N4
• InChI: 1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+
• InChIKey: RITAVMQDGBJQJZ-FMIVXFBMSA-N
• PubChem CID: 6450551
• ChEBI ID: CHEBI:66910
• TTD Drug ID: D01ZRI
• VARIDT ID: DR00035
• INTEDE ID: DR0162
• DrugBank ID: DB06626

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.V559D (c.1676T>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.V559A (c.1676T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.V559G (c.1676T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.L576P (c.1727T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.V654A (c.1961T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.T670I (c.2009C>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.A829P (c.2485G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Tyrosine-protein kinase ABL1 (ABL1) [3]

• Molecule Alteration: Missense mutation; p.T315I (c.944C>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; N.A.
• Mechanism Description: The missense mutation p.T315I (c.944C>T) in gene ABL1 cause the sensitivity of Axitinib by aberration of the drug's therapeutic target

Gastrointestinal cancer [ICD-11: 2B5B]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.V559D (c.1676T>A)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: IF-deletion; p.V560_Y578del19 (c.1679_1735del57)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.K642E (c.1924A>G)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

References

• Ref 1: Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma .Front Immunol. 2021 Oct 26;12:728750. doi: 10.3389/fimmu.2021.728750. eCollection 2021. 10.3389/fimmu.2021.728750
• Ref 2: Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumorsTher Adv Med Oncol. 2019 May 17;11:1758835919849757. doi: 10.1177/1758835919849757. eCollection 2019.
• Ref 3: Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformationNature. 2015 Mar 5;519(7541):102-5. doi: 10.1038/nature14119. Epub 2015 Feb 9.