Drug Information

Drug (ID: DG01906) and It's Reported Resistant Information

• Name: INU-152
• Synonyms: INU-152
• Target: .; NOUNIPROTAC; [1]

Type(s) of Resistant Mechanism of This Drug

  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

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: SkMEL2 cells; Skin; Homo sapiens (Human); CVCL_0069
• In Vitro Model: Colo-205 cells; Ascites; Homo sapiens (Human); CVCL_0218
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: INU-152 inhibits all RAF isoforms and inhibits MAPK pathways in mutant BRAF cells. More importantly, INU-152 exhibits minimal paradoxical pathway activation in melanoma cells with mutant RAS. INU-152 exhibits anti-tumor activities in xenograft models carrying BRAF mutations.

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: SkMEL2 cells; Skin; Homo sapiens (Human); CVCL_0069
• In Vitro Model: Colo-205 cells; Ascites; Homo sapiens (Human); CVCL_0218
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: INU-152 inhibits all RAF isoforms and inhibits MAPK pathways in mutant BRAF cells. More importantly, INU-152 exhibits minimal paradoxical pathway activation in melanoma cells with mutant RAS. INU-152 exhibits anti-tumor activities in xenograft models carrying BRAF mutations.

References

• Ref 1: Discovery of a novel pan-RAF inhibitor with potent anti-tumor activity in preclinical models of BRAF(V600E) mutant cancerLife Sci. 2017 Aug 15;183:37-44. doi: 10.1016/j.lfs.2017.06.021. Epub 2017 Jun 21.