Drug Information

Drug (ID: DG01486) and It's Reported Resistant Information

• Name: Tandutinib
• Synonyms: Tandutinib; 387867-13-2; MLN-518; MLN518; CT53518; Tandutinib (MLN518); MLN 518; CT 53518; 4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide; UNII-E1IO3ICJ9A; CT-53518; N-(4-isopropoxyphenyl)-4-(6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-yl)piperazine-1-carboxamide; E1IO3ICJ9A; CHEMBL124660; CHEBI:90237; MLN-0518; MFCD09954147; NSC726292; NSC-759851; NCGC00241097-01; D06005; DSSTox_CID_28873; DSSTox_RID_83142; DSSTox_GSID_48947; 4-{6-methoxy-7-[3-(piperidin-1-yl)propoxy]quinazolin-4-yl}-N-[4-(propan-2-yloxy)phenyl]piperazine-1-carboxamide; CAS-387867-13-2; Tandutinib [USAN:INN]; tandutinibum; Kinome_3320; MLN518, Tandutinib; Tandutinib(MLN518); Tandutinib - MLN518; Tandutinib (USAN/INN); Tandutinib(CT 53518); MLS006010972; SCHEMBL927974; DTXSID8048947; BDBM13535; cid_3038522; AOB5045; SYN1088; TANDUTINIB (CT53518); BCPP000051; HMS3244A21; HMS3244A22; HMS3244B21; HMS3264G08; HMS3654O09; HMS3745A09; Pharmakon1600-01502277; AMY32698; BCP01370; EX-A1637; ZINC3966243; Tox21_113366; NSC759851; NSC760841; NSC800942; s1043; AKOS015902621; Tox21_113366_1; AC-1659; CCG-213017; CS-0128; DB05465; ES-0051; NSC 759851; NSC-726292; NSC-760841; NSC-800942; SB19380; NCGC00241097-02; NCGC00241097-03; NCGC00241097-07; HY-10202; SMR004702776; B1526; FT-0653217; SW218125-2; EC-000.2262; Tandutinib pound MLN518, CT53518 pound(c); AB01562955_01; 867T132; A824282; Q-201778; BRD-K89162000-001-01-5; Q27095683; MLN518;CT53518;MLN 518;CT 53518;MLN-518;CT-53518; 1-Piperazinecarboxamide, 4-(6-methoxy-7-(3-(1-piperidinyl)propoxy)-4-quinazolinyl)-N-(4-(1-methylethoxy)phenyl)-; 1227636-17-0; 4-(6-Methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-yl)-N-(4-(1-methylethoxy)phenyl)piperazine-1-carboxamide; 4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-[4-(1-methylethoxy)phenyl]piperazine-1-carboxamide; 4-[6-methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinyl]-N-(4-propan-2-yloxyphenyl)-1-piperazinecarboxamide; 4-[6-Methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinyl]-N-[4-(1-methylethoxy)phenyl]-1-piperazinecarboxamide; 4-[7-(3-Piperidin-1-yl-propoxy)-quinazolin-4-yl]-piperazine-1-carboxylic acid (4-isopropoxy-phenyl)-amide; N-(4-isopropoxyphenyl)-4-[6-methoxy-7-(3-piperidinopropoxy)quinazolin-4-yl]piperazine-1-carboxamide
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Discontinued in Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Acute myeloid leukemia [ICD-11: 2A60]; [2]
• Target: .; NOUNIPROTAC; [2]
• Formula: 10
• IsoSMILES: CC(C)OC1=CC=C(C=C1)NC(=O)N2CCN(CC2)C3=NC=NC4=CC(=C(C=C43)OC)OCCCN5CCCCC5
• InChI: InChI=1S/C31H42N6O4/c1-23(2)41-25-10-8-24(9-11-25)34-31(38)37-17-15-36(16-18-37)30-26-20-28(39-3)29(21-27(26)32-22-33-30)40-19-7-14-35-12-5-4-6-13-35/h8-11,20-23H,4-7,12-19H2,1-3H3,(H,34,38)
• InChIKey: UXXQOJXBIDBUAC-UHFFFAOYSA-N
• PubChem CID: 3038522
• ChEBI ID: CHEBI:90237
• TTD Drug ID: D0PI3Z
• DrugBank ID: DB05465

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  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

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [2]

• Molecule Alteration: IF-deletion; p.I836delI (c.2508_2510delCAT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Celltiter96AQueousOne solution proliferation assay
• Mechanism Description: The if-deletion p.I836delI (c.2508_2510delCAT) in gene FLT3 cause the sensitivity of Tandutinib by aberration of the drug's therapeutic target.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]

• Molecule Alteration: Missense mutation; p.V559D (c.1676T>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: ELISA assay
• Mechanism Description: The missense mutation p.V559D (c.1676T>A) in gene KIT cause the sensitivity of Tandutinib by unusual activation of pro-survival pathway

Acute myeloid leukemia [ICD-11: 2A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [2]

• Molecule Alteration: Missense mutation; p.D835V (c.2504A>T)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Celltiter96AQueousOne solution proliferation assay
• Mechanism Description: The missense mutation p.D835V (c.2504A>T) in gene FLT3 cause the resistance of Tandutinib by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [3]

• Molecule Alteration: Duplication; p.R595_L601 (c.1783_1803)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: MOLM-13 cells; Peripheral blood; Homo sapiens (Human); CVCL_2119
• In Vitro Model: MOLM-14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: KG1a cells; Pleural effusion; Homo sapiens (Human); CVCL_1824
• In Vitro Model: RS4 cells; Bone marrow; Homo sapiens (Human); CVCL_0093
• In Vitro Model: AML193 cells; Peripheral blood; Homo sapiens (Human); CVCL_1071
• In Vivo Model: Athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Kinase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The duplication p.R595_L601 (c.1783_1803) in gene FLT3 cause the sensitivity of Tandutinib by aberration of the drug's therapeutic target.

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [3]

• Molecule Alteration: IF-insertion; p.E598_Y599insGLVQVTGSSDNEYFYVDFREYE (c.1794_1795insGGTCTTGTACAAGTAACAGGTAGCAGCGACAACGAGTATTTTTATGTAGACTTTAGGGAGTATGAG)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: MOLM-13 cells; Peripheral blood; Homo sapiens (Human); CVCL_2119
• In Vitro Model: MOLM-14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: KG1a cells; Pleural effusion; Homo sapiens (Human); CVCL_1824
• In Vitro Model: RS4 cells; Bone marrow; Homo sapiens (Human); CVCL_0093
• In Vitro Model: AML193 cells; Peripheral blood; Homo sapiens (Human); CVCL_1071
• In Vivo Model: Athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Kinase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The if-insertion p.E598_Y599insGLVQVTGSSDNEYFYVDFREYE (c.1794_1795insGGTCTTGTACAAGTAACAGGTAGCAGCGACAACGAGTATTTTTATGTAGACTTTAGGGAGTATGAG) in gene FLT3 cause the sensitivity of Tandutinib by aberration of the drug's therapeutic target.

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [3]

• Molecule Alteration: IF-insertion; p.Y599_D600insGLYVDFREYEY (c.1798_1799insGTCTTTATGTAGACTTTAGGGAGTATGAGTATG)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: MOLM-13 cells; Peripheral blood; Homo sapiens (Human); CVCL_2119
• In Vitro Model: MOLM-14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: KG1a cells; Pleural effusion; Homo sapiens (Human); CVCL_1824
• In Vitro Model: RS4 cells; Bone marrow; Homo sapiens (Human); CVCL_0093
• In Vitro Model: AML193 cells; Peripheral blood; Homo sapiens (Human); CVCL_1071
• In Vivo Model: Athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Kinase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The if-insertion p.Y599_D600insGLYVDFREYEY (c.1798_1799insGTCTTTATGTAGACTTTAGGGAGTATGAGTATG) in gene FLT3 cause the sensitivity of Tandutinib by aberration of the drug's therapeutic target.

References

• Ref 1: Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinasesProc Natl Acad Sci U S A. 2005 Aug 2;102(31):11011-6. doi: 10.1073/pnas.0504952102. Epub 2005 Jul 26.
• Ref 2: Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518Blood. 2004 Nov 1;104(9):2867-72. doi: 10.1182/blood-2003-12-4446. Epub 2004 Jul 15.
• Ref 3: CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML)Cancer Cell. 2002 Jun;1(5):421-32. doi: 10.1016/s1535-6108(02)00070-3.