DDInter1666 DDInter448
In eliciting its mechanism of action, sildenafil ultimately prevents or minimizes the breakdown of cyclic guanosine monophosphate (cGMP) by inhibiting cGMP specific phosphodiesterase type 5 (PDE5) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The result of doing so allows cGMP present in both the penis and pulmonary vasculature to elicit smooth muscle relaxation and vasodilation that subsequently facilitates relief in pulmonary arterial hypertension and the increased flow of blood into the spongy erectile tissue of the penis that consequently allows it to grow in size and become erect and rigid [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Interestingly enough, it is precisely via this mechanism why sildenafil was at first researched as a potential treatment
Crizotinib is a tyrosine kinase receptor inhibitor used for the treatment of anaplastic lymphoma kinase (ALK) or ROS1-positive non-small cell lung cancer (NSCLC) tumors, as well as ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT). By targeting the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein, crizotinib offers robust effectiveness in treating NSCLC in patients with this type of rearrangement. Crizotinib was the first-in-class drug used to treat ALK-positive tumors. Second- and third-generation ALK-tyrosine kinase-inhibitors have overcome many of the pharmacodynamic and genetic resistance mechanisms crizotinib is prone to. Crizotinib was approved by the FDA in 2011, and its use is accompanied by FDA-approved tests used to detect ALK and ROS1 rearrangements.
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Crizotinib
Sildenafil {u} (Compound) downregulates {v} (Gene) CYCS
CYCS {u} (Gene) is downregulated by {v} (Compound) Crizotinib
Sildenafil {u} (Compound) causes {v} (Side Effect) Fatigue
Fatigue {u} (Side Effect) is caused by {v} (Compound) Crizotinib
Sildenafil {u} (Compound) resembles {v} (Compound) Vardenafil
Vardenafil {u} may lead to a major life threatening interaction when taken with {v} Crizotinib
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) covaries with {v} (Gene) PTK2B
PTK2B {u} (Gene) is bound by {v} (Compound) Crizotinib
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A5
CYP3A5 {u} (Gene) regulates {v} (Gene) CDK7
CDK7 {u} (Gene) is bound by {v} (Compound) Crizotinib
Sildenafil {u} (Compound) downregulates {v} (Gene) CYCS
CYCS {u} (Gene) is regulated by {v} (Gene) ABL2
ABL2 {u} (Gene) is bound by {v} (Compound) Crizotinib
Sildenafil {u} (Compound) causes {v} (Side Effect) Fatigue
Fatigue {u} (Side Effect) is caused by {v} (Compound) Modafinil
Modafinil {u} may cause a minor interaction that can limit clinical effects when taken with {v} Crizotinib
Sildenafil {u} (Compound) causes {v} (Side Effect) Visual acuity reduced
Visual acuity reduced {u} (Side Effect) is caused by {v} (Compound) Timolol
Timolol {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Crizotinib
Sildenafil {u} (Compound) causes {v} (Side Effect) Upper respiratory tract infection
Upper respiratory tract infection {u} (Side Effect) is caused by {v} (Compound) Mirabegron
Mirabegron {u} may cause a minor interaction that can limit clinical effects when taken with {v} Crizotinib
Sildenafil (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Crizotinib (Compound)
Sildenafil (Compound) downregulates CYCS (Gene) and CYCS (Gene) is downregulated by Crizotinib (Compound)
Sildenafil (Compound) causes Fatigue (Side Effect) and Fatigue (Side Effect) is caused by Crizotinib (Compound)
Sildenafil (Compound) resembles Vardenafil (Compound) and Vardenafil may lead to a major life threatening interaction when taken with Crizotinib
Sildenafil (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) covaries with PTK2B (Gene) and PTK2B (Gene) is bound by Crizotinib (Compound)
Sildenafil (Compound) binds CYP3A5 (Gene) and CYP3A5 (Gene) regulates CDK7 (Gene) and CDK7 (Gene) is bound by Crizotinib (Compound)
Sildenafil (Compound) downregulates CYCS (Gene) and CYCS (Gene) is regulated by ABL2 (Gene) and ABL2 (Gene) is bound by Crizotinib (Compound)
Sildenafil (Compound) causes Fatigue (Side Effect) and Fatigue (Side Effect) is caused by Modafinil (Compound) and Modafinil may cause a minor interaction that can limit clinical effects when taken with Crizotinib
Sildenafil (Compound) causes Visual acuity reduced (Side Effect) and Visual acuity reduced (Side Effect) is caused by Timolol (Compound) and Timolol may cause a moderate interaction that could exacerbate diseases when taken with Crizotinib
Sildenafil (Compound) causes Upper respiratory tract infection (Side Effect) and Upper respiratory tract infection (Side Effect) is caused by Mirabegron (Compound) and Mirabegron may cause a minor interaction that can limit clinical effects when taken with Crizotinib