DDInter150 DDInter1352
Azathioprine is a prodrug of 6-mercaptopurine, first synthesized in 1956 by Gertrude Elion, William Lange, and George Hitchings in an attempt to produce a derivative of 6-mercaptopurine with a better therapeutic index.[A189678,A189687,A189690] Azathioprine is used to treat inflammatory conditions like rheumatoid arthritis and as an immunosuppressant in the prevention of renal transplant rejection. Azathiprine was granted FDA approval on 20 March 1968.
Osimertinib is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) drug developed by AstraZeneca Pharmaceuticals.[A7926,L43453] Its use is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in cases where tumour EGFR expression is positive for the T790M mutation as detected by FDA-approved testing and which has progressed following therapy with a first-generation EGFR tyrosine kinase inhibitor. Approximately 10% of patients with NSCLC have a rapid and clinically effective response to EGFR-TKIs due to the presence of specific activating EGFR mutations within the tumour cells. More specifically, deletions around the LREA motif in exon 19 and exon 21 L858R point mutations are correlated with response to therapy. Development of third-generation EGFR-TKIs, such as osimertinib, has been in response to altered tumour resistance patterns following treatment and toxic side effects that impact patient quality of life. Treatment with first-generation EGFR-TKIs (gefitinib and erlotinib) has been associated with the development of resistance through activating mutations in the EGFR gene. Second-generation EGFR-TKIs (afatinib and dacomitinib) were then developed to be more potent inhibitors, although their use is associated with increased toxicity through nonspecific targeting of wild-type EGFR. In contrast, third-generation inhibitors are specific for the gate-keeper T790M mutations which increases ATP binding activity to EGFR and result in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.[A7926,A7927,A7931]
Azathioprine {u} (Compound) treats {v} (Disease) systemic lupus erythematosus
systemic lupus erythematosus {u} (Disease) is treated by {v} (Compound) Leflunomide
Leflunomide {u} may lead to a major life threatening interaction when taken with {v} Osimertinib
Azathioprine {u} (Compound) treats {v} (Disease) Crohn's disease
Crohn's disease {u} (Disease) is treated by {v} (Compound) Sulfasalazine
Sulfasalazine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Azathioprine {u} (Compound) treats {v} (Disease) rheumatoid arthritis
rheumatoid arthritis {u} (Disease) is palliated by {v} (Compound) Lidocaine
Lidocaine {u} may cause a minor interaction that can limit clinical effects when taken with {v} Osimertinib
Azathioprine {u} (Compound) treats {v} (Disease) systemic lupus erythematosus
systemic lupus erythematosus {u} (Disease) is palliated by {v} (Compound) Amitriptyline
Amitriptyline {u} may lead to a major life threatening interaction when taken with {v} Osimertinib
Azathioprine {u} (Compound) binds {v} (Gene) HPRT1
HPRT1 {u} (Gene) is upregulated by {v} (Compound) Tetrabenazine
Tetrabenazine {u} may lead to a major life threatening interaction when taken with {v} Osimertinib
Azathioprine {u} (Compound) treats {v} (Disease) multiple sclerosis
multiple sclerosis {u} (Disease) is palliated by {v} (Compound) Oxcarbazepine
Oxcarbazepine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Azathioprine {u} (Compound) binds {v} (Gene) XDH
XDH {u} (Gene) is bound by {v} (Compound) Daunorubicin
Daunorubicin {u} may lead to a major life threatening interaction when taken with {v} Osimertinib
Azathioprine {u} (Compound) binds {v} (Gene) HPRT1
HPRT1 {u} (Gene) is downregulated by {v} (Compound) Simvastatin
Simvastatin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Azathioprine {u} (Compound) binds {v} (Gene) HPRT1
HPRT1 {u} (Gene) is downregulated by {v} (Compound) Granisetron
Granisetron {u} may lead to a major life threatening interaction when taken with {v} Osimertinib
Azathioprine {u} (Compound) binds {v} (Gene) TPMT
TPMT {u} (Gene) is upregulated by {v} (Compound) Topotecan
Topotecan {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Azathioprine (Compound) treats systemic lupus erythematosus (Disease) and systemic lupus erythematosus (Disease) is treated by Leflunomide (Compound) and Leflunomide may lead to a major life threatening interaction when taken with Osimertinib
Azathioprine (Compound) treats Crohn's disease (Disease) and Crohn's disease (Disease) is treated by Sulfasalazine (Compound) and Sulfasalazine may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Azathioprine (Compound) treats rheumatoid arthritis (Disease) and rheumatoid arthritis (Disease) is palliated by Lidocaine (Compound) and Lidocaine may cause a minor interaction that can limit clinical effects when taken with Osimertinib
Azathioprine (Compound) treats systemic lupus erythematosus (Disease) and systemic lupus erythematosus (Disease) is palliated by Amitriptyline (Compound) and Amitriptyline may lead to a major life threatening interaction when taken with Osimertinib
Azathioprine (Compound) binds HPRT1 (Gene) and HPRT1 (Gene) is upregulated by Tetrabenazine (Compound) and Tetrabenazine may lead to a major life threatening interaction when taken with Osimertinib
Azathioprine (Compound) treats multiple sclerosis (Disease) and multiple sclerosis (Disease) is palliated by Oxcarbazepine (Compound) and Oxcarbazepine may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Azathioprine (Compound) binds XDH (Gene) and XDH (Gene) is bound by Daunorubicin (Compound) and Daunorubicin may lead to a major life threatening interaction when taken with Osimertinib
Azathioprine (Compound) binds HPRT1 (Gene) and HPRT1 (Gene) is downregulated by Simvastatin (Compound) and Simvastatin may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Azathioprine (Compound) binds HPRT1 (Gene) and HPRT1 (Gene) is downregulated by Granisetron (Compound) and Granisetron may lead to a major life threatening interaction when taken with Osimertinib
Azathioprine (Compound) binds TPMT (Gene) and TPMT (Gene) is upregulated by Topotecan (Compound) and Topotecan may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib