DDInter1666 DDInter1678
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
Sirolimus, also known as rapamycin, is a macrocyclic lactone antibiotic produced by bacteria _Streptomyces hygroscopicus_, which was isolated from the soil of the Vai Atari region of Rapa Nui (Easter Island). It was first isolated and identified as an antifungal agent with potent anticandida activity; however, after its potent antitumor and immunosuppressive activities were later discovered, it was extensively investigated as an immunosuppressive and antitumour agent. Its primary mechanism of action is the inhibition of the mammalian target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that regulates cell growth, proliferation, and survival. mTOR is an important therapeutic target for various diseases, as it was shown to regulate longevity and maintain normal glucose homeostasis. Targeting mTOR received more attention especially in cancer, as mTOR signalling pathways are constitutively activated in many types of human cancer. Sirolimus was first approved by the FDA in 1999 for the prophylaxis of organ rejection in patients aged 13 years and older receiving renal transplants. In November 2000, the drug was recognized by the European Agency as an alternative to calcineurin antagonists for maintenance therapy with corticosteroids. In May 2015, the FDA approved sirolimus for the treatment of patients with lymphangioleiomyomatosis. In November 2021, albumin-bound sirolimus for intravenous injection was approved by the FDA for the treatment of adults with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa). Sirolimus was also investigated in other cancers such as skin cancer, Kaposi’s Sarcoma, cutaneous T-cell lymphomas, and tuberous sclerosis. The topical formulation of sirolimus, marketed as HYFTOR, was approved by the FDA in April 2022: this marks the first topical treatment approved in the US for facial angiofibroma associated with tuberous sclerosis complex.
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A7-CYP3A51P
CYP3A7-CYP3A51P {u} (Gene) is bound by {v} (Compound) Sirolimus
Sildenafil {u} (Compound) binds {v} (Gene) ABCC5
ABCC5 {u} (Gene) is upregulated by {v} (Compound) Sirolimus
Sildenafil {u} (Compound) downregulates {v} (Gene) CYCS
CYCS {u} (Gene) is downregulated by {v} (Compound) Sirolimus
Sildenafil {u} (Compound) causes {v} (Side Effect) Constipation
Constipation {u} (Side Effect) is caused by {v} (Compound) Sirolimus
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A7-CYP3A51P
CYP3A7-CYP3A51P {u} (Gene) is bound by {v} (Compound) Tacrolimus
Tacrolimus {u} (Compound) resembles {v} (Compound) Sirolimus
Sildenafil {u} (Compound) binds {v} (Gene) ABCC5
ABCC5 {u} (Gene) is upregulated by {v} (Compound) Everolimus
Everolimus {u} (Compound) resembles {v} (Compound) Sirolimus
Sildenafil {u} (Compound) downregulates {v} (Gene) CYCS
CYCS {u} (Gene) is downregulated by {v} (Compound) Temsirolimus
Temsirolimus {u} (Compound) resembles {v} (Compound) Sirolimus
Sildenafil {u} (Compound) causes {v} (Side Effect) Constipation
Constipation {u} (Side Effect) is caused by {v} (Compound) Pimecrolimus
Pimecrolimus {u} (Compound) resembles {v} (Compound) Sirolimus
Sildenafil {u} (Compound) causes {v} (Side Effect) Testicular disorder
Testicular disorder {u} (Side Effect) is caused by {v} (Compound) Lansoprazole
Lansoprazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Sirolimus
Sildenafil {u} (Compound) causes {v} (Side Effect) Pulmonary haemorrhage
Pulmonary haemorrhage {u} (Side Effect) is caused by {v} (Compound) Cilostazol
Cilostazol {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Sirolimus
Sildenafil (Compound) binds CYP3A7-CYP3A51P (Gene) and CYP3A7-CYP3A51P (Gene) is bound by Sirolimus (Compound)
Sildenafil (Compound) binds ABCC5 (Gene) and ABCC5 (Gene) is upregulated by Sirolimus (Compound)
Sildenafil (Compound) downregulates CYCS (Gene) and CYCS (Gene) is downregulated by Sirolimus (Compound)
Sildenafil (Compound) causes Constipation (Side Effect) and Constipation (Side Effect) is caused by Sirolimus (Compound)
Sildenafil (Compound) binds CYP3A7-CYP3A51P (Gene) and CYP3A7-CYP3A51P (Gene) is bound by Tacrolimus (Compound) and Tacrolimus (Compound) resembles Sirolimus (Compound)
Sildenafil (Compound) binds ABCC5 (Gene) and ABCC5 (Gene) is upregulated by Everolimus (Compound) and Everolimus (Compound) resembles Sirolimus (Compound)
Sildenafil (Compound) downregulates CYCS (Gene) and CYCS (Gene) is downregulated by Temsirolimus (Compound) and Temsirolimus (Compound) resembles Sirolimus (Compound)
Sildenafil (Compound) causes Constipation (Side Effect) and Constipation (Side Effect) is caused by Pimecrolimus (Compound) and Pimecrolimus (Compound) resembles Sirolimus (Compound)
Sildenafil (Compound) causes Testicular disorder (Side Effect) and Testicular disorder (Side Effect) is caused by Lansoprazole (Compound) and Lansoprazole may cause a moderate interaction that could exacerbate diseases when taken with Sirolimus
Sildenafil (Compound) causes Pulmonary haemorrhage (Side Effect) and Pulmonary haemorrhage (Side Effect) is caused by Cilostazol (Compound) and Cilostazol may cause a moderate interaction that could exacerbate diseases when taken with Sirolimus