Biological Pathway: Reactome:R-HSA-9665230

Drug resistance in ERBB2 KD mutants related metabolites

find 8 related metabolites which is associated with the biological pathway Drug resistance in ERBB2 KD mutants

this pathway object is a organism specific pathway, which is related to taxonomy Homo sapiens (human).

ERBB2 kinase domain (KD) mutants vary in their resistance to various tyrosine kinase inhibitors and therapeutic antibody trastuzumab (herceptin). The following ERBB2 KD mutants are resistant to the therapeutic antibody trastuzumab (herceptin):

ERBB2 L755P (Nagano et al. 2018);
ERBB2 L755S (Nagano et al. 2018);
ERBB2 I767M (Bose et al. 2013);
ERBB2 D769Y (Nagano et al. 2018);
ERBB2 V777L (Nagano et al. 2018);
ERBB2 G778_P780dup (Bose et al. 2013, Nagano et al. 2018);
ERBB2 T798M (Rexer et al. 2013);
ERBB2 V842I (Nagano et al. 2018);
ERBB2 T862A (Nagano et al. 2018);
ERBB2 L869R (Hanker et al. 2017);

For ERBB2 R896C, both resistance (Bose et al. 2013) and sensitivity (Nagano et al. 2018) to trastuzumab have been reported.

Lapatinib

N-(3-Chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-(((2-(methylsulphonyl)ethyl)amino)methyl)-2-furanyl)-4-quinazolinamine

C29H26ClFN4O4S (580.1347238000001)

Lapatinib is an anti-cancer drug developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug Capecitabine. Lapatinib is human epidermal growth factor receptor type 2 (HER2/ERBB2) and epidermal growth factor receptor (HER1/EGFR/ERBB1) tyrosine kinases inhibitor. It binds to the intracellular phosphorylation domain to prevent receptor autophosphorylation upon ligand binding. L - Antineoplastic and immunomodulating agents > L01 - Antineoplastic agents > L01E - Protein kinase inhibitors > L01EH - Human epidermal growth factor receptor 2 (her2) tyrosine kinase inhibitors C274 - Antineoplastic Agent > C2189 - Signal Transduction Inhibitor > C129824 - Antineoplastic Protein Inhibitor C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C163952 - EGFR-targeting Agent C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C163760 - HER2-targeting Agent C471 - Enzyme Inhibitor > C1404 - Protein Kinase Inhibitor > C1967 - Tyrosine Kinase Inhibitor C471 - Enzyme Inhibitor > C129825 - Antineoplastic Enzyme Inhibitor > C159156 - HER2 Inhibitor D004791 - Enzyme Inhibitors > D047428 - Protein Kinase Inhibitors D000970 - Antineoplastic Agents

Osimertinib

N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide

C28H33N7O2 (499.2695598)

Lapatinib

C29H26ClFN4O4S (580.1347238000001)

L - Antineoplastic and immunomodulating agents > L01 - Antineoplastic agents > L01E - Protein kinase inhibitors > L01EH - Human epidermal growth factor receptor 2 (her2) tyrosine kinase inhibitors C274 - Antineoplastic Agent > C2189 - Signal Transduction Inhibitor > C129824 - Antineoplastic Protein Inhibitor C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C163952 - EGFR-targeting Agent C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C163760 - HER2-targeting Agent C471 - Enzyme Inhibitor > C1404 - Protein Kinase Inhibitor > C1967 - Tyrosine Kinase Inhibitor C471 - Enzyme Inhibitor > C129825 - Antineoplastic Enzyme Inhibitor > C159156 - HER2 Inhibitor D004791 - Enzyme Inhibitors > D047428 - Protein Kinase Inhibitors D000970 - Antineoplastic Agents CONFIDENCE standard compound; INTERNAL_ID 2525

AEE788 (NVP-AEE788)

(R)-6-(4-((4-Ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

C27H32N6 (440.26883119999997)

C471 - Enzyme Inhibitor > C1404 - Protein Kinase Inhibitor > C1967 - Tyrosine Kinase Inhibitor

afatinib

C24H25ClFN5O3 (485.1629862)

L - Antineoplastic and immunomodulating agents > L01 - Antineoplastic agents > L01E - Protein kinase inhibitors > L01EB - Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors C274 - Antineoplastic Agent > C2189 - Signal Transduction Inhibitor > C129824 - Antineoplastic Protein Inhibitor C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C163952 - EGFR-targeting Agent C471 - Enzyme Inhibitor > C1404 - Protein Kinase Inhibitor > C1967 - Tyrosine Kinase Inhibitor C471 - Enzyme Inhibitor > C129825 - Antineoplastic Enzyme Inhibitor D004791 - Enzyme Inhibitors > D047428 - Protein Kinase Inhibitors D000970 - Antineoplastic Agents (E/Z)-Afatinib ((E/Z)-BIBW 2992) is the mixture of (E)-Afatinib and (Z)-Afatinib. Afatinib (HY-10261) is an irreversible inhibitor of EGFR, by irreversibly binding to their ATP binding site to block activation of EGFR, HER2, HER4, and EGFRvIII. Afatinib used in co-administration with Temozolomide (HY-17364), potently targeting to EGFRvIII-cMet signaling in glioblastoma cells[1]. Afatinib (BIBW 2992) is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC50 values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively. Afatinib can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer[1][2][3][4].

Sapitinib

C23H25ClFN5O3 (473.1629862)

XL-647

Tesevatinib

C24H25Cl2FN4O2 (490.1338501999999)

C274 - Antineoplastic Agent > C2189 - Signal Transduction Inhibitor > C129824 - Antineoplastic Protein Inhibitor C471 - Enzyme Inhibitor > C1404 - Protein Kinase Inhibitor > C1967 - Tyrosine Kinase Inhibitor C471 - Enzyme Inhibitor > C129825 - Antineoplastic Enzyme Inhibitor D004791 - Enzyme Inhibitors > D047428 - Protein Kinase Inhibitors C274 - Antineoplastic Agent > C1742 - Angiogenesis Inhibitor D000970 - Antineoplastic Agents

AZD-9291

Osimertinib

C28H33N7O2 (499.2695598)