DDInter1233 DDInter1678
Mitotane is an adrenolytic isomer of the insecticide dichlorodiphenyldichloroethane (DDD) - itself a metabolite of dichlorodiphenyltrichloroethane (DDT) - that inhibits cells of the adrenal cortex and their production of hormones. It has been in use since 1959 for the treatment of inoperable adrenocortical carcinoma and is used off-label for the management of Cushing's syndrome.
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.
Mitotane {u} (Compound) downregulates {v} (Gene) DNMT3A
DNMT3A {u} (Gene) is upregulated by {v} (Compound) Sirolimus
Mitotane {u} (Compound) causes {v} (Side Effect) Tremor
Tremor {u} (Side Effect) is caused by {v} (Compound) Sirolimus
Mitotane {u} (Compound) downregulates {v} (Gene) DNMT3A
DNMT3A {u} (Gene) is upregulated by {v} (Compound) Temsirolimus
Temsirolimus {u} (Compound) resembles {v} (Compound) Sirolimus
Mitotane {u} (Compound) causes {v} (Side Effect) Tremor
Tremor {u} (Side Effect) is caused by {v} (Compound) Tacrolimus
Tacrolimus {u} (Compound) resembles {v} (Compound) Sirolimus
Mitotane {u} (Compound) resembles {v} (Compound) Carbinoxamine
Carbinoxamine {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Sirolimus
Mitotane {u} (Compound) downregulates {v} (Gene) DNMT3A
DNMT3A {u} (Gene) is regulated by {v} (Gene) KLHDC2
KLHDC2 {u} (Gene) is upregulated by {v} (Compound) Sirolimus
Mitotane {u} (Compound) causes {v} (Side Effect) Orthostatic hypotension
Orthostatic hypotension {u} (Side Effect) is caused by {v} (Compound) Eplerenone
Eplerenone {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Sirolimus
Mitotane {u} (Compound) resembles {v} (Compound) Delorazepam
Delorazepam {u} (Compound) resembles {v} (Compound) Flurazepam
Flurazepam {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Sirolimus
Mitotane {u} (Compound) resembles {v} (Compound) Carbinoxamine
Carbinoxamine {u} (Compound) downregulates {v} (Gene) DNMT3A
DNMT3A {u} (Gene) is upregulated by {v} (Compound) Sirolimus
Mitotane {u} (Compound) causes {v} (Side Effect) Hepatocellular injury
Hepatocellular injury {u} (Side Effect) is caused by {v} (Compound) Ezetimibe
Ezetimibe {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Sirolimus
Mitotane (Compound) downregulates DNMT3A (Gene) and DNMT3A (Gene) is upregulated by Sirolimus (Compound)
Mitotane (Compound) causes Tremor (Side Effect) and Tremor (Side Effect) is caused by Sirolimus (Compound)
Mitotane (Compound) downregulates DNMT3A (Gene) and DNMT3A (Gene) is upregulated by Temsirolimus (Compound) and Temsirolimus (Compound) resembles Sirolimus (Compound)
Mitotane (Compound) causes Tremor (Side Effect) and Tremor (Side Effect) is caused by Tacrolimus (Compound) and Tacrolimus (Compound) resembles Sirolimus (Compound)
Mitotane (Compound) resembles Carbinoxamine (Compound) and Carbinoxamine (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Sirolimus (Compound)
Mitotane (Compound) downregulates DNMT3A (Gene) and DNMT3A (Gene) is regulated by KLHDC2 (Gene) and KLHDC2 (Gene) is upregulated by Sirolimus (Compound)
Mitotane (Compound) causes Orthostatic hypotension (Side Effect) and Orthostatic hypotension (Side Effect) is caused by Eplerenone (Compound) and Eplerenone may cause a moderate interaction that could exacerbate diseases when taken with Sirolimus
Mitotane (Compound) resembles Delorazepam (Compound) and Delorazepam (Compound) resembles Flurazepam (Compound) and Flurazepam may cause a moderate interaction that could exacerbate diseases when taken with Sirolimus
Mitotane (Compound) resembles Carbinoxamine (Compound) and Carbinoxamine (Compound) downregulates DNMT3A (Gene) and DNMT3A (Gene) is upregulated by Sirolimus (Compound)
Mitotane (Compound) causes Hepatocellular injury (Side Effect) and Hepatocellular injury (Side Effect) is caused by Ezetimibe (Compound) and Ezetimibe may cause a moderate interaction that could exacerbate diseases when taken with Sirolimus