Active Ingredient History
Sirolimus is the USAN-assigned generic name for the natural product rapamycin. Sirolimus is produced by a strain of Streptomyces hygroscopicus, isolated from a soil sample collected from Rapa Nui commonly known as Easter Island. Although sirolimus was isolated as an antifungal agent with potent anticandida activity, subsequent studies revealed impressive antitumor and immunosuppressive activities. Sirolimus demonstrates activity against several murine tumors, such as B16 43 melanocarcinoma, Colon 26 tumor, EM ependymoblastoma, and mammary and colon 38 solid tumors. Demonstration of the potent immunosuppressive activity of sirolimus in animal models of organ transplantation led to clinical trials and subsequent approval by regulatory authorities for prophylaxis of renal graft rejection. Interest in sirolimus as an immunosuppressive therapy in organ transplantation derives from its unique mechanism of action, its unique side-effect profile, and its ability to synergize with other immunosuppressive agents. It is used in medicine to prevent organ transplant rejection and to treat lymphangioleiomyomatosis. Sirolimus inhibits T-lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukin [IL]-2, IL-4, and IL-15) stimulation by a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. This complex blocks the activation of the cell-cycle-specific kinase, TOR. The downstream events that follow the inactivation of TOR result in the blockage of cell-cycle progression at the juncture of G1 and S phase. Rapamycin/FKBP12 efficiently inhibit some, but not all, functions of mTOR and hence much interest has been placed in the development of drugs that target the kinase activity of mTOR directly. Studies in experimental models show that sirolimus prolongs allograft (kidney, heart, skin, islet, small bowel, pancreatico-duodenal, and bone marrow) survival in mice, rats, pigs, and/or primates. Sirolimus reverses acute rejection of heart and kidney allografts in rats and prolongs the graft survival in presensitized rats. In some studies, the immunosuppressive effect of sirolimus lasts up to 6 months after discontinuation of therapy. This tolerization effect is alloantigen-specific. In rodent models of autoimmune disease, sirolimus suppresses immune-mediated events associated with systemic lupus erythematosus, collagen-induced arthritis, autoimmune type I diabetes, autoimmune myocarditis, experimental allergic encephalomyelitis, graft-versus-host disease, and autoimmune uveoretinitis. Lymphangioleiomyomatosis involves lung tissue infiltration with smooth muscle-like cells that harbor inactivating mutations of the tuberous sclerosis complex (TSC) gene (LAM cells). Loss of TSC gene function activates the mTOR signaling pathway, resulting in cellular proliferation and release of lymphangiogenic growth factors. Sirolimus inhibits the activated mTOR pathway and thus the proliferation of LAM cells. NCATS
Drug Pricing (per unit)
Note: This drug pricing data is preliminary, incomplete, and may contain errors.
| Organization | Org Type | FDA approvals | Clinical Trials involvement | Org ID | Force Sort |
|---|
| Organization | Org Type | FDA approvals | Clinical Trials involvement | Org ID | Force Sort |
|---|
Lymphangioleiomyomatosis (approved 1999)
Acne Vulgaris (Phase 3)
Acute-On-Chronic Liver Failure (Phase 2)
Adenocarcinoma, Clear Cell (Phase 1)
Adenocarcinoma of Lung (Phase 1/Phase 2)
Adenomatous Polyposis Coli (Phase 2)
Aged (Phase 4)
Aging (Phase 4)
Alcoholism (Phase 1)
Allogeneic Cells (Phase 2)
Allografts (Phase 4)
Alzheimer Disease (Phase 2)
Amyotrophic Lateral Sclerosis (Phase 2)
Anaplasia (Phase 4)
Anemia (Phase 1)
Anemia, Aplastic (Phase 2)
Anemia, Hemolytic, Autoimmune (Phase 2/Phase 3)
Anemia, Hemolytic, Congenital (Phase 2)
Anemia, Sickle Cell (Phase 2)
Angina Pectoris (Phase 4)
Angiofibroma (Phase 3)
Angiomatosis (Phase 4)
Angiomyolipoma (Phase 4)
Arteriovenous Fistula (Phase 3)
Arteriovenous Malformations (Phase 2)
Arthritis, Rheumatoid (Phase 1/Phase 2)
Astrocytoma (Phase 1)
Atherosclerosis (Phase 3)
Atrophy (Phase 1/Phase 2)
Autistic Disorder (Phase 2)
Autoimmune Diseases (Phase 2)
beta-Thalassemia (Phase 2)
Birt-Hogg-Dube Syndrome (Phase 3)
Blood (Phase 2)
Bone Marrow Failure Disorders (Phase 2)
Brain Neoplasms (Phase 1/Phase 2)
Breast Neoplasms (Phase 2)
Bronchiolitis (Phase 2)
Bronchitis (Phase 2)
Burkitt Lymphoma (Phase 2)
Carcinoma, Basal Cell (Phase 1/Phase 2)
Carcinoma, Hepatocellular (Phase 3)
Carcinoma, Merkel Cell (Phase 1/Phase 2)
Carcinoma, Non-Small-Cell Lung (Phase 1/Phase 2)
Carcinoma, Renal Cell (Phase 2)
Carcinoma, Squamous Cell (Phase 2)
Carcinoma, Transitional Cell (Phase 1)
Cardiomegaly (Phase 1)
Cardiovascular Abnormalities (Phase 3)
Castleman Disease (Phase 2)
CCR5 Receptor Antagonists (Phase 4)
Central Nervous System Neoplasms (Phase 1)
Chondrosarcoma (Phase 2)
Chondrosarcoma, Mesenchymal (Phase 2)
Choroidal Neovascularization (Phase 2)
Chromosome Aberrations (Phase 1)
Cigarette Smoking (Phase 2)
Cognitive Dysfunction (Phase 2)
Colorectal Neoplasms (Phase 1)
Common Variable Immunodeficiency (Phase 2)
Comparative Study (Phase 4)
Connective Tissue Diseases (Phase 4)
Coronary Artery Disease (Phase 4)
Coronary Disease (Phase 4)
Coronary Restenosis (Phase 4)
COVID-19 (Phase 2/Phase 3)
Crohn Disease (Phase 4)
Cytomegalovirus Infections (Phase 4)
Delayed Graft Function (Phase 4)
Depression (Phase 2)
Diabetes Mellitus, Type 1 (Phase 4)
Diabetic Nephropathies (Phase 3)
Diabetic Retinopathy (Phase 1/Phase 2)
Drug Interactions (Phase 1)
Drug Resistant Epilepsy (Phase 1)
Drugs, Generic (Phase 1)
Dry Eye Syndromes (Phase 2)
Endometrial Neoplasms (Phase 2)
End Stage Liver Disease (Phase 3)
Eosinophilic Esophagitis (Phase 1)
Ependymoma (Phase 1)
Epidermolysis Bullosa Simplex (Phase 2)
Epilepsy (Phase 2)
Epistaxis (Phase 2)
Esophageal Neoplasms (Phase 1)
Eye Infections (Phase 3)
Fallopian Tube Neoplasms (Phase 1)
Fanconi Anemia (Phase 2/Phase 3)
Fibrosis (Phase 4)
Gastroenteritis (Phase 1)
Gaucher Disease (Phase 1/Phase 2)
Genetic Diseases, Inborn (Phase 2)
Genetic Predisposition to Disease (Phase 1)
Genetics (Phase 2)
Geographic Atrophy (Phase 2)
Glioblastoma (Phase 2)
Glioma (Phase 2)
Gliosarcoma (Phase 2)
Glomerular Filtration Rate (Phase 4)
Glomerulonephritis, IGA (Phase 2)
Glomerulonephritis, Membranous (Phase 2)
Glomerulosclerosis, Focal Segmental (Phase 2)
Glycogen Storage Disease Type II (Phase 1)
Gout (Phase 2)
Graft Rejection (Phase 4)
Graft vs Host Disease (Phase 4)
Granulomatous Disease, Chronic (Phase 1/Phase 2)
Graves Ophthalmopathy (Phase 2)
Growth and Development (Phase 2)
Growth Disorders (Phase 2)
Hamartoma (Phase 2)
Hamartoma Syndrome, Multiple (Phase 2)
Head and Neck Neoplasms (Phase 1/Phase 2)
Healthy Volunteers (Phase 1)
Heart Failure (Phase 1)
Heart Transplantation (Phase 4)
Hemangioendothelioma (Phase 4)
Hemangioma (Phase 4)
Hematologic Diseases (Phase 2)
Hematologic Neoplasms (Phase 2)
Hematopoietic Stem Cell Transplantation (Phase 2)
Hemodialysis, Home (Phase 3)
Hemoglobinuria, Paroxysmal (Phase 4)
Hepatitis C (Phase 4)
Hepatoblastoma (Phase 1)
Herpesvirus 8, Human (Phase 2)
HIV (Phase 4)
HIV Infections (Phase 4)
Hodgkin Disease (Phase 3)
Hypercholesterolemia (Phase 1)
Hyperinsulinism (Phase 1/Phase 2)
Hypertension (Phase 4)
Hypertension, Pulmonary (Phase 2)
Hyperuricemia (Phase 2)
Hypoglycemia (Phase 2)
Hypoxia (Phase 2)
Immune System Diseases (Phase 2)
Immunosuppression Therapy (Phase 4)
Immunosuppressive Agents (Phase 4)
Infections (Phase 2)
Inflammation (Phase 4)
Inflammatory Bowel Diseases (Phase 1/Phase 2)
Influenza A Virus, H1N1 Subtype (Phase 2)
Influenza, Human (Phase 4)
Intestinal Neoplasms (Phase 2)
Intestinal Polyposis (Phase 2)
Intracranial Aneurysm (Phase 2)
Kasabach-Merritt Syndrome (Phase 4)
Kidney Diseases (Phase 4)
Kidney Failure, Chronic (Phase 4)
Kidney Neoplasms (Phase 1)
Kidney Transplantation (Phase 4)
Leigh Disease (Phase 2)
Leiomyoma (Phase 4)
Leukemia (Phase 2)
Leukemia, Biphenotypic, Acute (Phase 2)
Leukemia, Lymphocytic, Chronic, B-Cell (Phase 3)
Leukemia, Lymphoid (Phase 1/Phase 2)
Leukemia-Lymphoma, Adult T-Cell (Phase 2)
Leukemia, Monocytic, Acute (Phase 2)
Leukemia, Myeloid (Phase 2)
Leukemia, Myeloid, Accelerated Phase (Phase 2)
Leukemia, Myeloid, Acute (Phase 3)
Leukemia, Myeloid, Chronic-Phase (Phase 2)
Leukemia, Myelomonocytic, Acute (Phase 2)
Leukemia, Myelomonocytic, Chronic (Phase 2)
Leukemia, Myelomonocytic, Juvenile (Phase 2)
Leukemia, Plasma Cell (Phase 2)
Leukemia, Prolymphocytic (Phase 3)
Leukemia, Prolymphocytic, T-Cell (Phase 3)
Lichen Planus, Oral (Phase 3)
Liposarcoma, Myxoid (Phase 2)
Liver Diseases (Phase 2/Phase 3)
Liver Neoplasms (Phase 2/Phase 3)
Liver Transplantation (Phase 4)
Lung Diseases (Phase 3)
Lung Neoplasms (Phase 1/Phase 2)
Lung Transplantation (Phase 2)
Lupus Erythematosus, Systemic (Phase 2)
Lupus Nephritis (Phase 2/Phase 3)
Lymphangioleiomyomatosis (Phase 3)
Lymphatic Diseases (Phase 4)
Lymphoid Tissue (Phase 2)
Lymphoma (Phase 3)
Lymphoma, B-Cell (Phase 2)
Lymphoma, B-Cell, Marginal Zone (Phase 2)
Lymphoma, Follicular (Phase 2/Phase 3)
Lymphoma, Large B-Cell, Diffuse (Phase 3)
Lymphoma, Large-Cell, Anaplastic (Phase 2)
Lymphoma, Large-Cell, Immunoblastic (Phase 2)
Lymphoma, Mantle-Cell (Phase 3)
Lymphoma, Non-Hodgkin (Phase 3)
Lymphoma, T-Cell (Phase 2)
Lymphoma, T-Cell, Peripheral (Phase 2)
Lymphoproliferative Disorders (Phase 2)
Macular Degeneration (Phase 2)
Macular Edema (Phase 2)
Medulloblastoma (Phase 1)
Melanins (Phase 3)
Melanoma (Phase 1/Phase 2)
Metabolic Diseases (Phase 2)
Mouth Neoplasms (Phase 1/Phase 2)
Multiple Myeloma (Phase 3)
Multiple Sclerosis (Phase 1/Phase 2)
Multiple System Atrophy (Phase 2)
Mutation (Phase 2)
Mycoses (Phase 2)
Myelodysplastic Syndromes (Phase 3)
Myeloproliferative Disorders (Phase 3)
Myocardial Infarction (Phase 4)
Myositis (Phase 2/Phase 3)
Myositis, Inclusion Body (Phase 3)
Nasopharyngeal Neoplasms (Phase 3)
Neoplasm Metastasis (Phase 2)
Neoplasm, Residual (Phase 2)
Neoplasms (Phase 4)
Neoplasms, Germ Cell and Embryonal (Phase 2)
Neoplasms, Plasma Cell (Phase 1)
Neoplastic Syndromes, Hereditary (Phase 1)
Nerve Sheath Neoplasms (Phase 1/Phase 2)
Neuroblastoma (Phase 2)
Neuroendocrine Tumors (Phase 2)
Neurofibroma (Phase 1)
Neurofibromatoses (Phase 3)
Neurofibromatosis 1 (Phase 2)
Neurofibrosarcoma (Phase 2)
Neutropenia (Phase 1/Phase 2)
Nevus (Phase 4)
Oligodendroglioma (Phase 1)
Osteosarcoma (Phase 2)
Ovarian Neoplasms (Phase 2)
Pachyonychia Congenita (Phase 1)
Pancreas Transplantation (Phase 4)
Pancreatic Neoplasms (Phase 2)
Panuveitis (Phase 2)
Pemphigus (Early Phase 1)
Peripheral Blood Stem Cell Transplantation (Phase 1/Phase 2)
Peutz-Jeghers Syndrome (Phase 4)
Pharmacokinetics (Phase 2/Phase 3)
Pharmacology (Phase 1)
Pinealoma (Phase 2)
Plasmacytoma (Phase 2)
Polycystic Kidney, Autosomal Dominant (Phase 3)
Polycystic Kidney Diseases (Phase 2/Phase 3)
Port-Wine Stain (Phase 1)
Precancerous Conditions (Phase 2)
Primary Immunodeficiency Diseases (Phase 2)
Primary Myelofibrosis (Phase 2)
Prostatic Neoplasms (Phase 2/Phase 3)
Prostatic Neoplasms, Castration-Resistant (Phase 1/Phase 2)
Prostheses and Implants (Phase 2)
Proteus Syndrome (Phase 2)
Pseudomyxoma Peritonei (Phase 2)
Pulmonary Fibrosis (Phase 2/Phase 3)
Purpura, Thrombocytopenic, Idiopathic (Phase 1/Phase 2)
Rectal Neoplasms (Phase 1/Phase 2)
Red-Cell Aplasia, Pure (Phase 4)
Renal Insufficiency (Phase 4)
Renal Insufficiency, Chronic (Phase 4)
Respiratory Distress Syndrome (Phase 1/Phase 2)
Respiratory Insufficiency (Phase 1/Phase 2)
Retinoblastoma (Phase 1)
Retroperitoneal Fibrosis (Phase 2/Phase 3)
Rhabdoid Tumor (Phase 1)
Rhabdomyosarcoma (Phase 1)
Sarcoidosis (Phase 2)
Sarcoma (Phase 2)
Sarcoma, Clear Cell (Phase 1)
Sarcoma, Ewing (Phase 2)
Sarcoma, Kaposi (Phase 4)
Sarcoma, Myeloid (Phase 2)
Sarcopenia (Phase 1)
SARS-CoV-2 (Phase 1)
Scleritis (Phase 1/Phase 2)
Scleroderma, Systemic (Phase 2)
Self-Injurious Behavior (Phase 2)
Severe Combined Immunodeficiency (Phase 2)
Sirolimus (Phase 1)
Skin Neoplasms (Phase 4)
Small Cell Lung Carcinoma (Phase 1/Phase 2)
Smoking Cessation (Phase 2)
Squamous Cell Carcinoma of Head and Neck (Phase 2)
Stem Cell Transplantation (Phase 1/Phase 2)
Stents (Phase 2)
Stomach Neoplasms (Phase 1)
Sturge-Weber Syndrome (Phase 2/Phase 3)
Survival (Phase 3)
Telangiectasia, Hereditary Hemorrhagic (Phase 2)
Thalassemia (Phase 1/Phase 2)
Thrombocytopenia (Phase 4)
Thyroid Neoplasms (Phase 2)
Tobacco Use Disorder (Phase 2)
Tongue Neoplasms (Phase 1/Phase 2)
Transplantation (Phase 4)
Transplantation, Homologous (Phase 1)
Tuberous Sclerosis (Phase 3)
Urinary Bladder Neoplasms (Phase 3)
Uterine Cervical Neoplasms (Phase 2)
Uterine Neoplasms (Phase 1)
Uveitis (Phase 3)
Uveitis, Anterior (Phase 1)
Uveitis, Intermediate (Phase 2)
Uveitis, Posterior (Phase 2)
Vascular Access Devices (Phase 3)
Vascular Diseases (Phase 4)
Vascular Grafting (Phase 2)
Vascular Malformations (Phase 3)
Venous Cutdown (Phase 4)
Waldenstrom Macroglobulinemia (Phase 3)
Wilms Tumor (Phase 1)
| Trial | Phase | Start Date | Organizations | Indications |
|---|
Feedback
Data collection and curation is an ongoing process for CDEK - if you notice any information here to be missing or incorrect, please let us know! When possible, please include a source URL (we verify all data prior to inclusion).
Report issue
