DDInter1666 DDInter484
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
Dasatinib is an orally available multikinase inhibitor indicated for the treatment of Philadelphia chromosome (Ph)-positive leukemias.[A2224,L45171] Ph is a chromosomal abnormality found in patients with chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL), where the ABL tyrosine kinase and the breakpoint cluster region (BCR) gene transcribe the chimeric protein BCR-ABL. BCR-ABL is associated with the uncontrolled activity of the ABL tyrosine kinase and is involved in the pathogenesis of CML and 15-30% of ALL cases.[A11377,A33432] Dasatinib also inhibits a spectrum of kinases involved in cancer, including several SRC-family kinases. Unlike [imatinib], another tyrosine kinase used for the treatment of CML and Ph-positive ALL, dasatinib inhibits the active and inactive conformations of the ABL kinase domain.[A2226,A11377] Also, mutations in the kinase domain of BCR-ABL may lead to relapse during imatinib treatment. Since dasatinib does not interact with some of the residues involved in those mutations, the use of this drug represents a therapeutic alternative for patients with cancers that have developed imatinib-resistance. The use of dasatinib was first approved by the FDA in 2006.[L45171,L45186]
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Dasatinib
Sildenafil {u} (Compound) binds {v} (Gene) ABCC5
ABCC5 {u} (Gene) is upregulated by {v} (Compound) Dasatinib
Sildenafil {u} (Compound) downregulates {v} (Gene) CYCS
CYCS {u} (Gene) is downregulated by {v} (Compound) Dasatinib
Sildenafil {u} (Compound) causes {v} (Side Effect) Body temperature increased
Body temperature increased {u} (Side Effect) is caused by {v} (Compound) Dasatinib
Sildenafil {u} (Compound) resembles {v} (Compound) Vardenafil
Vardenafil {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Dasatinib
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) covaries with {v} (Gene) FMO3
FMO3 {u} (Gene) is bound by {v} (Compound) Dasatinib
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A5
CYP3A5 {u} (Gene) regulates {v} (Gene) HERC6
HERC6 {u} (Gene) is upregulated by {v} (Compound) Dasatinib
Sildenafil {u} (Compound) binds {v} (Gene) ABCC5
ABCC5 {u} (Gene) is regulated by {v} (Gene) LCK
LCK {u} (Gene) is bound by {v} (Compound) Dasatinib
Sildenafil {u} (Compound) downregulates {v} (Gene) CYCS
CYCS {u} (Gene) is associated with {v} (Disease) hematologic cancer
hematologic cancer {u} (Disease) is treated by {v} (Compound) Dasatinib
Sildenafil {u} (Compound) causes {v} (Side Effect) Body temperature increased
Body temperature increased {u} (Side Effect) is caused by {v} (Compound) Sulfamethoxazole
Sulfamethoxazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Dasatinib
Sildenafil (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Dasatinib (Compound)
Sildenafil (Compound) binds ABCC5 (Gene) and ABCC5 (Gene) is upregulated by Dasatinib (Compound)
Sildenafil (Compound) downregulates CYCS (Gene) and CYCS (Gene) is downregulated by Dasatinib (Compound)
Sildenafil (Compound) causes Body temperature increased (Side Effect) and Body temperature increased (Side Effect) is caused by Dasatinib (Compound)
Sildenafil (Compound) resembles Vardenafil (Compound) and Vardenafil may cause a moderate interaction that could exacerbate diseases when taken with Dasatinib
Sildenafil (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) covaries with FMO3 (Gene) and FMO3 (Gene) is bound by Dasatinib (Compound)
Sildenafil (Compound) binds CYP3A5 (Gene) and CYP3A5 (Gene) regulates HERC6 (Gene) and HERC6 (Gene) is upregulated by Dasatinib (Compound)
Sildenafil (Compound) binds ABCC5 (Gene) and ABCC5 (Gene) is regulated by LCK (Gene) and LCK (Gene) is bound by Dasatinib (Compound)
Sildenafil (Compound) downregulates CYCS (Gene) and CYCS (Gene) is associated with hematologic cancer (Disease) and hematologic cancer (Disease) is treated by Dasatinib (Compound)
Sildenafil (Compound) causes Body temperature increased (Side Effect) and Body temperature increased (Side Effect) is caused by Sulfamethoxazole (Compound) and Sulfamethoxazole may cause a minor interaction that can limit clinical effects when taken with Dasatinib