DDInter1233 DDInter1659
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.
Activation of the Raf-MEK-ERK signalling pathway is known to be implemented in several types of malignancies; thus, mitogen-activated protein kinase kinase (MEK) inhibitors such as selumetinib are important tools that can target the problematic overactivity of this pathway. Results from clinical trials investigating earlier developed MEK inhibitors were underwhelming. However, selumetinib demonstrated impressive efficacy and tolerability in Phase I trials, leading to its continued investigation for the treatment of various types of tumours in Phase II trials. Currently, the novel MEK 1 / 2 inhibitor, selumetinib, is approved solely for the treatment of Neurofibromatosis type 1 (NF-1) in a limited age group. NF-1 is considered rare, with an estimated incidence of 1/3000 individuals. It is a genetic, autosomal dominant condition resulting from mutations of the NF1 gene, which can lead to various complications, including the development of multiple tumours in the nervous system.[A193533,A193608] Some patients with this disorder develop plexiform neurofibromas (PN); however, this is considered relatively uncommon compared to other variants of NF-1. Luckily, the use of selumetinib in patients with NF-1 have shown efficacy in shrinking associated tumours and is linked to other positive clinical outcomes. Selumetinib was approved by the FDA on April 10, 2020. It was later approved by Health Canada on August 23, 2022.
Mitotane {u} (Compound) causes {v} (Side Effect) Confusional state
Confusional state {u} (Side Effect) is caused by {v} (Compound) Argatroban
Argatroban {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Mitotane {u} (Compound) causes {v} (Side Effect) Digestion impaired
Digestion impaired {u} (Side Effect) is caused by {v} (Compound) Imatinib
Imatinib {u} may lead to a major life threatening interaction when taken with {v} Selumetinib
Mitotane {u} (Compound) binds {v} (Gene) CYP11B1
CYP11B1 {u} (Gene) is bound by {v} (Compound) Cimetidine
Cimetidine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Mitotane {u} (Compound) binds {v} (Gene) CYP11B1
CYP11B1 {u} (Gene) is bound by {v} (Compound) Fluconazole
Fluconazole {u} may lead to a major life threatening interaction when taken with {v} Selumetinib
Mitotane {u} (Compound) upregulates {v} (Gene) AGR2
AGR2 {u} (Gene) is upregulated by {v} (Compound) Treprostinil
Treprostinil {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Mitotane {u} (Compound) downregulates {v} (Gene) NVL
NVL {u} (Gene) is downregulated by {v} (Compound) Treprostinil
Treprostinil {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Mitotane {u} (Compound) upregulates {v} (Gene) EIF4EBP1
EIF4EBP1 {u} (Gene) is downregulated by {v} (Compound) Treprostinil
Treprostinil {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Mitotane {u} (Compound) downregulates {v} (Gene) NVL
NVL {u} (Gene) is upregulated by {v} (Compound) Clopidogrel
Clopidogrel {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Mitotane {u} (Compound) upregulates {v} (Gene) AGR2
AGR2 {u} (Gene) is upregulated by {v} (Compound) Clarithromycin
Clarithromycin {u} may lead to a major life threatening interaction when taken with {v} Selumetinib
Mitotane {u} (Compound) downregulates {v} (Gene) NVL
NVL {u} (Gene) is downregulated by {v} (Compound) Dexamethasone
Dexamethasone {u} may lead to a major life threatening interaction when taken with {v} Selumetinib
Mitotane (Compound) causes Confusional state (Side Effect) and Confusional state (Side Effect) is caused by Argatroban (Compound) and Argatroban may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Mitotane (Compound) causes Digestion impaired (Side Effect) and Digestion impaired (Side Effect) is caused by Imatinib (Compound) and Imatinib may lead to a major life threatening interaction when taken with Selumetinib
Mitotane (Compound) binds CYP11B1 (Gene) and CYP11B1 (Gene) is bound by Cimetidine (Compound) and Cimetidine may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Mitotane (Compound) binds CYP11B1 (Gene) and CYP11B1 (Gene) is bound by Fluconazole (Compound) and Fluconazole may lead to a major life threatening interaction when taken with Selumetinib
Mitotane (Compound) upregulates AGR2 (Gene) and AGR2 (Gene) is upregulated by Treprostinil (Compound) and Treprostinil may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Mitotane (Compound) downregulates NVL (Gene) and NVL (Gene) is downregulated by Treprostinil (Compound) and Treprostinil may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Mitotane (Compound) upregulates EIF4EBP1 (Gene) and EIF4EBP1 (Gene) is downregulated by Treprostinil (Compound) and Treprostinil may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Mitotane (Compound) downregulates NVL (Gene) and NVL (Gene) is upregulated by Clopidogrel (Compound) and Clopidogrel may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Mitotane (Compound) upregulates AGR2 (Gene) and AGR2 (Gene) is upregulated by Clarithromycin (Compound) and Clarithromycin may lead to a major life threatening interaction when taken with Selumetinib
Mitotane (Compound) downregulates NVL (Gene) and NVL (Gene) is downregulated by Dexamethasone (Compound) and Dexamethasone may lead to a major life threatening interaction when taken with Selumetinib