the halogenated phenyl group. About 86% of the drug is removed via faeces

whereas 4–5% is metabolized via renal route (Rawluk and Waller 2018).

21.3.2 Erlotinib

Erlotinib is a quinazoline-based small molecule EGFR inhibitor. It was approved by

the FDA in 2004 for the treatment of pancreatic and NSCLC. Erlotinib acts by

binding to the active conformation of EGFR. The chemical structure of the drug is

given in Fig. 21.2. The drug is administered through oral route with 60% oral

bioavailability. After about 4 h, the drug reaches to its peak plasma concentration

with an apparent volume of distribution of 232 L. After reaching to systemic

circulation, 92–94% of the drug gets bound to the albumin and glycoprotein.

CYP3A4 is the hepatic enzyme involved in the biotransformation of the drug.

After biotransformation, 80–82% of the drug is eliminated through faeces and

8–10% of the drug is eliminated via renal route (Abdelgalil et al. 2019).

21.3.3 Lapatinib

Lapatinib is a quinazoline-based small molecule EGFR inhibitor. It was approved by

the FDA in 2007 for the treatment of HER2-positive breast cancer and lung cancer.

The chemical structure of the drug is given in Fig. 21.2. Gefitinib and erlotinib act by

binding to the active site or conformation of the EGFR, lapatinib acts by binding the

inactive conformation of the receptor. Lapatinib is a dual inhibitor and inhibits two

oncogenes, HER2 and EGFR. The drug is given through oral route with varying

rates of intestinal reabsorption. After 3–6 h of administration, the drug reaches to its

peak plasma concentration. The drug attains the protein binding of >99% after

reaching to systemic circulation. Biotransformation of the drug is done by the

hepatic enzyme CYP3A4. About 14% of the drug is eliminated by anal route and

10% via urine (Voigtlaender et al. 2018).

Fig. 21.2 Quinazoline-based

nucleus as a parent moiety

substituted at R1, R2 and R3

21

EGFR-Targeted Quinazoline Clubbed Heterocycles as Anticancer Agents

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