Drug Information

Drug (ID: DG01561) and It's Reported Resistant Information

• Name: CCT196969
• Synonyms: CCT196969; 1163719-56-9; 1-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl)-3-(2-fluoro-4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)phenyl)urea; CHEMBL4216588; 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea; GTPL9815; SCHEMBL3761639; BCP19551; EX-A1598; BDBM50457449; MFCD28384201; s7743; ZINC43205799; AKOS027422849; CCG-269799; CCT-196969; CS-6229; HY-12846; 1-(3-(t-Butyl)-1-phenyl-1H-pyrazol-5-yl)-3-(2-fluoro-4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)phenyl)urea; 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-fluoro-4-(3-oxo-3,4-dihydropyrido[3,2-b]pyrazin-8-yloxy)phenyl)urea
• Formula: 6
• IsoSMILES: CC(C)(C)C1=NN(C(=C1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C(=NC=C3)NC(=O)C=N4)F)C5=CC=CC=C5
• InChI: InChI=1S/C27H24FN7O3/c1-27(2,3)21-14-22(35(34-21)16-7-5-4-6-8-16)32-26(37)31-19-10-9-17(13-18(19)28)38-20-11-12-29-25-24(20)30-15-23(36)33-25/h4-15H,1-3H3,(H,29,33,36)(H2,31,32,37)
• InChIKey: KYYKGSDLXXKQCR-UHFFFAOYSA-N
• PubChem CID: 42628843

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

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

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• 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: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.V600D (c.1799_1800delTGinsAC)
• Experimental Note: Identified from the Human Clinical Data

Unusual Activation of Pro-survival Pathway (UAPP)

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: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vivo Model: Female xenograft nude mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Sanger Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; Tumor volume measurement assay

Key Molecule: GTPase Nras (NRAS) [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.Q61L (c.182A>T)
• Experimental Note: Identified from the Human Clinical Data

References

• Ref 1: Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanomaCancer Cell. 2015 Jan 12;27(1):85-96. doi: 10.1016/j.ccell.2014.11.006. Epub 2014 Dec 11.
• Ref 2: Tumor necrosis factor-alpha blocks apoptosis in melanoma cells when BRAF signaling is inhibitedCancer Res. 2007 Jan 1;67(1):122-9. doi: 10.1158/0008-5472.CAN-06-1880.