Drug Information

Drug (ID: DG01650) and It's Reported Resistant Information

• Name: PZ-1
• Synonyms: Pz-1; Pz-1, >=98% (HPLC); 1800505-64-9; N-(5-tert-butyl-1,2-oxazol-3-yl)-2-[4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]acetamide; SCHEMBL17315095; HY-U00437; NSC792733; ZINC526061663; NSC-792733; CS-0035381; B0084-267746
• Target: .; NOUNIPROTAC; [1]
• Formula: 6
• IsoSMILES: CC(C)(C)C1=CC(=NO1)NC(=O)CC2=CC=C(C=C2)N3C=NC4=C3C=CC(=C4)C5=CN(N=C5)C
• InChI: InChI=1S/C26H26N6O2/c1-26(2,3)23-13-24(30-34-23)29-25(33)11-17-5-8-20(9-6-17)32-16-27-21-12-18(7-10-22(21)32)19-14-28-31(4)15-19/h5-10,12-16H,11H2,1-4H3,(H,29,30,33)
• InChIKey: NJLMIILZNLZZFW-UHFFFAOYSA-N
• PubChem CID: 102004343

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [1]

• Molecule Alteration: Missense mutation; p.V804M (c.2410G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Microfluidic separation based assay

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [1]

• Molecule Alteration: Missense mutation; p.V804L (c.2410G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Microfluidic separation based assay

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [1]

• Molecule Alteration: Missense mutation; p.M918T (c.2753T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Microfluidic separation based assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [1]

• Molecule Alteration: Missense mutation; p.G12V (c.35G>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Microfluidic separation based assay

References

• Ref 1: Fragment-Based Discovery of a Dual pan-RET/VEGFR2 Kinase Inhibitor Optimized for Single-Agent PolypharmacologyAngew Chem Int Ed Engl. 2015 Jul 20;54(30):8717-21. doi: 10.1002/anie.201501104. Epub 2015 Jun 30.