Drug Information

Drug (ID: DG01564) and It's Reported Resistant Information

• Name: CCT241161
• Synonyms: CCT241161; 1163719-91-2; CHEMBL4204895; 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-(methylthio)-4-(3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)phenyl)urea; 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-[2-methylsulfanyl-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea; GTPL9814; SCHEMBL3173602; BDBM50457448; CCT241161 pan RAF/SFK inhibitor; AKOS037653304; GS-9003
• Formula: 7
• IsoSMILES: CC(C)(C)C1=NN(C(=C1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C(=NC=C3)NC(=O)C=N4)SC)C5=CC=CC=C5
• InChI: InChI=1S/C28H27N7O3S/c1-28(2,3)22-15-23(35(34-22)17-8-6-5-7-9-17)32-27(37)31-19-11-10-18(14-21(19)39-4)38-20-12-13-29-26-25(20)30-16-24(36)33-26/h5-16H,1-4H3,(H,29,33,36)(H2,31,32,37)
• InChIKey: DPMYVVGAYAPQNS-UHFFFAOYSA-N
• PubChem CID: 44132853

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

Colorectal cancer [ICD-11: 2B91]

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: 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

Aberration of the Drug's Therapeutic Target (ADTT)

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.