Drug Information

Drug (ID: DG01522) and It's Reported Resistant Information

• Name: AZ628
• Synonyms: 878739-06-1; AZ 628; AZ-628; AZ628; 3-(2-Cyanopropan-2-yl)-N-(4-methyl-3-((3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)phenyl)benzamide; AZD628; UNII-560S6B5D79; 3-(2-cyanopropan-2-yl)-N-(4-methyl-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylamino)phenyl)benzamide; 3-(1-Cyano-1-methylethyl)-N-[3-[(3,4-dihydro-3-methyl-4-oxo-6-quinazolinyl)amino]-4-methylphenyl]benzamide; 3-(Cyano-dimethyl-methyl)-N-[4-methyl-3-(3-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylamino)-phenyl]-benzamide; CHEMBL2144069; 3-(2-cyanopropan-2-yl)-N-[4-methyl-3-[(3-methyl-4-oxoquinazolin-6-yl)amino]phenyl]benzamide; 560S6B5D79; C27H25N5O2; 3-(2-Cyanopropan-2-Yl)-N-{4-Methyl-3-[(3-Methyl-4-Oxo-3,4-Dihydroquinazolin-6-Yl)amino]phenyl}benzamide; B1E; MLS006010314; GTPL8475; SCHEMBL4209241; CHEBI:91354; DTXSID70236677; EX-A302; QCR-186; HMS3265I11; HMS3265I12; HMS3265J11; HMS3265J12; HMS3656F21; HMS3743G19; BCP02117; BDBM50430022; MFCD17392577; NSC782007; s2746; ZINC38226503; AKOS016011304; BCP9000346; CCG-264992; CS-0091; NSC-782007; SB19421; NCGC00250380-01; NCGC00250380-03; NCGC00250380-10; AC-26863; Benzamide, 3-(1-cyano-1-methylethyl)-N-(3-((3,4-dihydro-3-methyl-4-oxo-6-quinazolinyl)amino)-4-methylphenyl)-; BS-42436; HY-11004; SMR004701380; FT-0700393; SW219448-1; Y0332; J-510421; BRD-K05804044-001-01-1; Q27074677; 3-(1-Cyano-1-methylethyl)-N-{4-methyl-3-[(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino]phenyl}benzamide
• Indication:
  In total 1 Indication(s)
  Non-small-cell lung cancer [ICD-11: 2C25]; Investigative; [1]
• Target: Platelet-derived growth factor receptor (PDGFR); NOUNIPROTAC; [1]
• Target: Tyrosine-protein kinase Kit (KIT); KIT_HUMAN; [1]
• Target: Vascular endothelial growth factor receptor 2 (KDR); VGFR2_HUMAN; [1]
• Formula: 5
• IsoSMILES: CC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)C(C)(C)C#N)NC3=CC4=C(C=C3)N=CN(C4=O)C
• InChI: InChI=1S/C27H25N5O2/c1-17-8-9-21(31-25(33)18-6-5-7-19(12-18)27(2,3)15-28)14-24(17)30-20-10-11-23-22(13-20)26(34)32(4)16-29-23/h5-14,16,30H,1-4H3,(H,31,33)
• InChIKey: ZGBGPEDJXCYQPH-UHFFFAOYSA-N
• PubChem CID: 11676786
• ChEBI ID: CHEBI:91354
• TTD Drug ID: D00DQX

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.55 Å; PDB: 4E26
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 3.20 Å; PDB: 4G9R

RMSD: 1.53; TM score: 0.95765; Amino acid change: V600E

• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: 8505C cells; Thyroid; Homo sapiens (Human); CVCL_1054
• In Vitro Model: Hth104 cells; Thyroid gland; Homo sapiens (Human); CVCL_A427
• In Vivo Model: Mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of AZ628 by aberration of the drug's therapeutic target

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.G466E (c.1397G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: 8505C cells; Thyroid; Homo sapiens (Human); CVCL_1054
• In Vitro Model: Hth104 cells; Thyroid gland; Homo sapiens (Human); CVCL_A427
• In Vivo Model: Mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.G466E (c.1397G>A) in gene BRAF cause the sensitivity of AZ628 by aberration of the drug's therapeutic target

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.V600R (c.1798_1799delGTinsAG)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: 8505C cells; Thyroid; Homo sapiens (Human); CVCL_1054
• In Vitro Model: Hth104 cells; Thyroid gland; Homo sapiens (Human); CVCL_A427
• In Vivo Model: Mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.V600R (c.1798_1799delGTinsAG) in gene BRAF cause the sensitivity of AZ628 by aberration of the drug's therapeutic target

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.V600D (c.1799_1800delTGinsAC)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: 8505C cells; Thyroid; Homo sapiens (Human); CVCL_1054
• In Vitro Model: Hth104 cells; Thyroid gland; Homo sapiens (Human); CVCL_A427
• In Vivo Model: Mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.V600D (c.1799_1800delTGinsAC) in gene BRAF cause the sensitivity of AZ628 by aberration of the drug's therapeutic target

References

• Ref 1: An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF SignalingCancer Cell. 2016 Sep 12;30(3):485-498. doi: 10.1016/j.ccell.2016.06.024. Epub 2016 Aug 11.