Inhibitors of Receptor Tyrosine Kinases

Question 1

RTK inhibitors

Answer 1

Imatinib
Ibrutinib
Afatinib
Ceritinib

Question 2

Imatinib

Answer 2

Gleevec
for CML or GI stromal tumor
at ATP site (INACTIVE) to get phosphate. PO take rest of life. Causes naus/vomit, edema, myelosupr. Causes Cardiotoxicity (not really tho)
–inhibits BCR-ABL TK. Induces apoptosis in BCRABL positive lines.
–Doesn’t deplete leukemic stem cells.
–Resistance develops in Philly chromosome +, from point mutation. Affect binding site or mode.
Inhibits 3A4, take with food.

Question 3

Ibrutinib

Answer 3

for mantle cell lymphoma or CLL, NHL (B-cell malignancies)
Bruton’s tyrosine kinase inhibitor
–Causes myelosuppression because need to kill B-cells
AEs: hemorrhage, myelosupr, infections, rash
Avoid CYP3A4 inh and ind

Question 4

Afatinib

Answer 4

for metastatic NSCLC with EGFR mutations. Inhibits EGFR and HER2

Question 5

Ceritinib

Answer 5

ALK+ MSCLC. Inhibits ALK and EML4-ALK+ nsclc that’s resistant to crizotinib.
–Inhibits angiogensis! Causes GI tox, hepatotox, cardiotox