Drug Information

Drug (ID: DG01871) and It's Reported Resistant Information

• Name: CYH33
• Synonyms: CYH33
• Indication:
  In total 1 Indication(s)
  Breast cancer [ICD-11: 2C60]; Phase 2; [1]
• Target: PI3-kinase alpha (PIK3CA); PK3CA_HUMAN; [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

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K signaling pathway; Inhibition; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: AU565 cells; Breast; Homo sapiens (Human); CVCL_1074
• In Vivo Model: MMTV-Cre mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Immunohistochemistry analysis
• Experiment for Drug Resistance: Sulforhodamine B assay; FACS assay
• Mechanism Description: Sensitivity to CYH33 has been further revealed to be associated with induction of G1 phase arrest and simultaneous inhibition of Akt and ERK. Sensitivity of patient-derived xenograft to CYH33 was also positively correlated with decrease in phosphorylated ERK. Taken together, CYH33 is a promising PI3Kalpha inhibitor for breast cancer treatment and decrease in ERK phosphorylation may indicate its efficacy, which provides useful clues for rational design of the ongoing clinical trials.

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.P539R (c.1616C>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K signaling pathway; Inhibition; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: AU565 cells; Breast; Homo sapiens (Human); CVCL_1074
• In Vivo Model: MMTV-Cre mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Immunohistochemistry analysis
• Experiment for Drug Resistance: Sulforhodamine B assay; FACS assay
• Mechanism Description: Sensitivity to CYH33 has been further revealed to be associated with induction of G1 phase arrest and simultaneous inhibition of Akt and ERK. Sensitivity of patient-derived xenograft to CYH33 was also positively correlated with decrease in phosphorylated ERK. Taken together, CYH33 is a promising PI3Kalpha inhibitor for breast cancer treatment and decrease in ERK phosphorylation may indicate its efficacy, which provides useful clues for rational design of the ongoing clinical trials.

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K signaling pathway; Inhibition; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: AU565 cells; Breast; Homo sapiens (Human); CVCL_1074
• In Vivo Model: MMTV-Cre mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Immunohistochemistry analysis
• Experiment for Drug Resistance: Sulforhodamine B assay; FACS assay
• Mechanism Description: Sensitivity to CYH33 has been further revealed to be associated with induction of G1 phase arrest and simultaneous inhibition of Akt and ERK. Sensitivity of patient-derived xenograft to CYH33 was also positively correlated with decrease in phosphorylated ERK. Taken together, CYH33 is a promising PI3Kalpha inhibitor for breast cancer treatment and decrease in ERK phosphorylation may indicate its efficacy, which provides useful clues for rational design of the ongoing clinical trials.

References

• Ref 1: Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3KAlpha-selective inhibitor CYH33 in breast cancerCancer Lett. 2018 Oct 1;433:273-282. doi: 10.1016/j.canlet.2018.07.011. Epub 2018 Jul 9.