Drug Information

Drug (ID: DG01521) and It's Reported Resistant Information

• Name: Motesanib
• Synonyms: Motesanib; 453562-69-1; AMG 706; AMG-706; N-(3,3-dimethylindolin-6-yl)-2-(pyridin-4-ylmethylamino)nicotinamide; AMG706; UNII-U1JK633AYI; N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)amino]pyridine-3-carboxamide; N-(2,3-Dihydro-3,3-dimethyl-1H-indol-6-yl)-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide; U1JK633AYI; CHEBI:51098; 453562-69-1 (free base); N-(2,3-dihydro-3,3-dimethyl-1H-indol-6-yl)-2-((4-pyridinylmethyl)amino)-3-pyridinecarboxamide; N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide; C22H23N5O; N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4- ylmethyl)amino]pyridine-3-carboxamide; Motesanib [USAN:INN]; N-(3,3-Dimethyl-2,3-dihydro-1H-indol-6-yl)-2-((pyridin-4-ylmethyl)amino)pyridine-3-carboxamide; Motesanib (USAN); AMG706/ Motesanib; Motesanib (AMG-706); SCHEMBL187470; CHEMBL572881; GTPL5660; QCR-80; BDBM24773; DTXSID10196488; EX-A487; SYN1055; cid_11667893; BCPP000407; HMS3244A09; HMS3244A10; HMS3244B09; HMS3265G19; HMS3265G20; HMS3265H19; HMS3265H20; AOB87176; BCP01982; AMG 706; AMG-706; MFCD10567689; NSC760843; NSC800801; s5793; ZINC18710082; AKOS005146333; N-(3,3-dimethylindolin-6-yl)-2-((pyridin-4-ylmethyl)amino)nicotinamide; BCP9000289; DB05575; EX-8571; NSC-760843; NSC-800801; SB14621; NCGC00263205-01; NCGC00263205-06; AC-32664; AS-16212; HY-10228; FT-0706483; X4931; A19395; D06678; 562M691; J-522983; Q6917202; BRD-K99616396-316-01-2; N-(3,3-dimethylindolin-6-yl)-2-(4-pyridylmethylamino)nicotinamide; N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)-3-pyridinecarboxamide; 3-Pyridinecarboxamide, N-(2,3-dihydro-3,3-dimethyl-1H-indol-6-yl)-2-((4-pyridinylmethyl)amino)-
• Indication:
  In total 1 Indication(s)
  Melanoma [ICD-11: 2C30]; Discontinued in Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Thyroid cancer [ICD-11: 2D10]; [1]
• Target: Vascular endothelial growth factor receptor 2 (KDR); VGFR2_HUMAN; [2]
• Formula: 5
• IsoSMILES: CC1(CNC2=C1C=CC(=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4)C
• InChI: InChI=1S/C22H23N5O/c1-22(2)14-26-19-12-16(5-6-18(19)22)27-21(28)17-4-3-9-24-20(17)25-13-15-7-10-23-11-8-15/h3-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28)
• InChIKey: RAHBGWKEPAQNFF-UHFFFAOYSA-N
• PubChem CID: 11667893
• ChEBI ID: CHEBI:51098
• TTD Drug ID: D03AND
• DrugBank ID: DB05575

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

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y823D (c.2467T>G)
• 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: BRAF kinase assay
• Mechanism Description: The missense mutation p.Y823D (c.2467T>G) in gene KIT cause the sensitivity of Motesanib by aberration of the drug's therapeutic target

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

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.M552_V559delMYEVQWKV (c.1654_1677del24)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Mechanism Description: The if-deletion p.M552_V559delMYEVQWKV (c.1654_1677del24) in gene KIT cause the sensitivity of Motesanib by aberration of the drug's therapeutic target.

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

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V560D (c.1679T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Mechanism Description: The missense mutation p.V560D (c.1679T>A) in gene KIT cause the sensitivity of Motesanib by aberration of the drug's therapeutic target

Thyroid cancer [ICD-11: 2D10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [1]

• Resistant Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Molecule Alteration: Missense mutation; p.M918T (c.2753T>C)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.64 Å; PDB: 7DUA
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.12 Å; PDB: 4CKI

RMSD: 0.93; TM score: 0.95555; Amino acid change: M918T

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Medullary thyroid cancer tissue; Pleural effusion; Homo sapiens (Human); CVCL_A656
• Mechanism Description: The missense mutation p.M918T (c.2753T>C) in gene RET cause the resistance of Motesanib by unusual activation of pro-survival pathway

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [1]

• Resistant Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Molecule Alteration: Missense mutation; p.C634W (c.1902C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Medullary thyroid cancer tissue; Pleural effusion; Homo sapiens (Human); CVCL_A656
• Mechanism Description: The missense mutation p.C634W (c.1902C>G) in gene RET cause the resistance of Motesanib by unusual activation of pro-survival pathway

References

• Ref 1: Anti-tumor activity of motesanib in a medullary thyroid cancer modelJ Endocrinol Invest. 2012 Feb;35(2):181-90. doi: 10.3275/7609. Epub 2011 Mar 21.
• Ref 2: Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumorsJ Exp Clin Cancer Res. 2010 Jul 15;29(1):96. doi: 10.1186/1756-9966-29-96.