Table 3 Summary information of 48 repurposing candidates for cystic fibrosis (CF) treatment

Simvastatin

Hypercholesterolemia; lower cholesterol

Simvastatin will increase nitric oxide (NO) produced (exhaled NO), and may decrease airway inflammation

NCT00255242

Pyruvic acid

Dietary shortage or imbalance

The inhalation of sodium pyruvate may reduce lung damage in patients with CF by its ability to reduce levels of toxic reactive oxygen and nitrogen compounds associated with the chronic inflammatory component of the disease

NCT00308243

Pioglitazone

Type 2 diabetes

Pioglitazone may decrease inflammation in CF lung disease

NCT00322868

l-Glutamine

Dietary shortage or imbalance

Patients with CF develop frequent and potentially life-threatening lung infections. The nutrient glutamine may help the body fight off infection

NCT01051999

Desipramine

Neuropathic pain; attention deficit hyperactivity disorder; anxiety disorders

Combination of desipramine and VX-770 for CF treatment

NCT01153542

Nitric oxide

Neonates with hypoxic respiratory failure

Exhaled nitric oxide (NO), elevated in most inflammatory lung diseases, is decreased in CF, suggesting decreased formation, increased metabolism or loss of NO

NCT00570349

PMID: 15982933

Choline

Dietary shortage or imbalance

Nutrition and methyl status of children with CF could be improved after supplying a choline supplement

NCT01070446

l-Leucine

Prevention of the breakdown of muscle proteins

A high-leucine essential amino acids mixture specifically designed to stimulate protein anabolism could target the metabolic alterations of pediatric subjects with CF

NCT01172301

Fluoxetine

Depression; obsessive-compulsive disorder; antiviral

It was suggested that a hydrophobic interaction with high affinity between uncharged fluoxetine and volume-activated chloride channels. Ca²⁺-activated Cl^- currents and CFTR are also blocked by fluoxetine, revealing a novel characteristic of the drug as a chloride channel modulator

PMID: 10077245

Cyclosporine

Transplant rejection; rheumatoid arthritis; severe psoriasis

These results suggest that cyclosporine can be beneficial as a steroid sparing agent in CF patients

PMID: 11213776

Morphine

Severe pain

Inhaled morphine to relieve dyspnea in patients with end-stage lung disease due to CF

PMID: 10973044

Methotrexate

Gestational choriocarcinoma; chorioadenoma destruens; hydatidiform mole; psoriasis; rheumatoid arthritis

It was suggested an effective systemic anti-inflammatory effect of methotrexate in treatment for CF patients with advanced pulmonary disease

PMID: 12735666

Vitamin C

Used to treat vitamin C deficiency, scurvy, delayed wound and bone healing, urine acidification, and in general as an antioxidant. It has also been suggested to be an effective antiviral agent

The pool of vitamin C in the respiratory tract represents a potential nutraceutical and pharmaceutical target for the complementary treatment of sticky airway secretions by enhancing epithelial fluid secretion

PMID: 14993613

Dexamethasone

Anti-inflammatory; oncologic uses; glucocorticoid resistance; obstetrics; high altitude illnesses

Low doses of dexamethasone constantly delivered by autologous erythrocytes slow the progression of lung disease in CF patients

PMID: 15223012

l-Arginine

Treating dietary shortage or imbalance

It was suggested that airway nitric oxide formation in CF patients can be augmented with oral L-arginine supplementation

PMID: 15640324

Tacrolimus

Atopic dermatitis; organ rejection

Tacrolimus was tested on lung transplantation of CF patients

PMID: 16372829

Tamoxifen

Breast cancer

This inhibition of Ca²⁺ signaling was prevented and even potentiated by estrogen antagonists such as tamoxifen, suggesting that antiestrogens may be beneficial in the treatment of CF lung disease because they increase Cl^- secretion in the airways

PMID: 19033671

Rosiglitazone

Type 2 diabetes

It was suggested rosiglitazone as important modulators of intestinal Cl- secretory function

PMID: 19443733

Vorinostat

Cutaneous T cell lymphoma

Vorinostat (SAHA) could restore surface channel activity in human primary airway epithelia to levels that are 28% of those of wild-type CFTR

PMID: 19966789

Metformin

Type 2 diabetes; prediabetes; polycystic ovary syndrome; gestational diabetes

The metabolic sensor AMP-activated kinase (AMPK) inhibits both the CFTR Cl(-) channel and epithelial Na(+) channel (ENaC), and may inhibit secretion of proinflammatory cytokines in epithelia

PMID: 19617399

Estradiol

Urogenital

17Beta-estradiol inhibits IL-8 release by ERbeta in CF bronchial epithelial cells through upregulation of secretory leucoprotease inhibitor, inhibition of nuclear factor (NF)-kappaB, and IL-8 gene expression. These data implicate a novel anti-inflammatory mechanism for E(2) in females with CF, which predisposes to infection and colonization

PMID: 20378727

Chloroquine

Malaria; strains of P. falciparum; rheumatoid arthritis

Vasculitis is a well recognized complication of CF. There is a case of steroid-resistant cutaneous vasculitis which was successfully treated with chloroquine in addition to corticosteroids and a subsequent relapse with chloroquine alone

PMID: 20863769

Sirolimus

Prophylaxis

Autophagy stimulation by sirolimus (rapamycin) suppresses lung inflammation and infection by Burkholderia cenocepacia in a model of CF

PMID: 21997369

Nifedipine

Vasospastic angina; chronic stable angina; hypertension; Raynaud’s phenomenon

Nifedipine may be a useful adjuvant to supplemental oxygen in the treatment of patients with CF and cor pulmonale

PMID: 6476600

Levamisole

Dukes’ stage C colon cancer; worm infestations

Levamisole could block K+ channels required for Cl(-)-secretory responses elicited by diverse pathways in model epithelia and native colon, an effect that outweighs their ability to activate apical Cl- channels

PMID: 9609763

Adenosine triphosphate

Dietary shortage or imbalance

It was reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal autocrine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors

PMID: 23757023

Imiquimod

non-hyperkeratotic; non-hypertrophic actinic keratoses

Phenobarbital

Seizures

Leucovorin

Osteosarcoma

Imatinib

Philadelphia chromosome positive chronic myeloid leukemia (CML); malignant gastrointestinal stromal tumors (GIST)

Gemcitabine

Metastatic breast cancer

Dienestrol

Atrophic vaginitis; kraurosis vulvae

Cyclophosphamide

Malignant lymphomas; multiple myeloma; leukemias

Chlorotrianisene

Menopause

Amiodarone

Cardiac dysrhythmias

Warfarin

Retinal vascular occlusion; pulmonary embolism; cardiomyopathy; atrial fibrillation and flutter; cerebral embolism; transient cerebral ischemia; arterial embolism; thrombosis

Paclitaxel

Kaposi’s sarcoma; cancer of the lung; ovarian and breast

Oxaliplatin

Cancer chemotherapy

Imipramine

Depression

Fluorouracil

Multiple actinic; solar keratoses

Mercaptopurine

Acute lymphatic leukemia

Cetuximab

EGFR-expressing metastatic colorectal cancer; squamous cell carcinoma

Dopamine

Hemodynamic imbalances

Vinblastine

Breast cancer; Hodgkin’s and non-Hodgkin’s lymphomas; Kaposi’s sarcoma

Adenosine monophosphate

Dietary shortage or imbalance