Sirolimus

Generic Name
Sirolimus
Brand Names
Fyarro, Hyftor, Rapamune
Drug Type
Small Molecule
Chemical Formula
C51H79NO13
CAS Number
53123-88-9
Unique Ingredient Identifier
W36ZG6FT64
Background

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.

Indication

Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. In patients at low-to moderate-immunologic risk, it is recommended that sirolimus be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn two to four months after transplantation. In patients at high-immunologic risk (defined as Black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [PRA; peak PRA level > 80%]), it is recommended that sirolimus be used in combination with cyclosporine and corticosteroids for the first year following transplantation.

It is also used to treat lymphangioleiomyomatosis.

In the US, albumin-bound sirolimus for intravenous injection is indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa).

In Europe, it is recommended that sirolimus for the prophylaxis of organ rejection in renal transplants is used in combination with cyclosporin microemulsion and corticosteroids for two to three months. Sirolimus may be continued as maintenance therapy with corticosteroids only if cyclosporin microemulsion can be progressively discontinued.

Topical sirolimus is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients six years of age and older.

Associated Conditions
Chordomas, Facial Angiofibroma, Graft-versus-host Disease (GVHD), Heart Transplant Rejection, Liver Transplant Rejection, Lung Transplant Rejection, Lymphangioleiomyomatosis (LAM), Renal Angiomyolipomas, Transplanted Organ Rejection, Metastatic malignant Perivascular Epithelioid Cell Neoplasms, Unresectable, locally advanced malignant Perivascular Epithelioid Cell Neoplasms
Associated Therapies
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Tolerance by Engaging Antigen During Cellular Homeostasis

First Posted Date
2018-04-20
Last Posted Date
2024-01-26
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Target Recruit Count
8
Registration Number
NCT03504241
Locations
🇺🇸

Duke University Health System, Durham, North Carolina, United States

Sirolimus-based Immunosuppression Treatment Regimen for Liver Transplantation

First Posted Date
2018-04-18
Last Posted Date
2018-04-18
Lead Sponsor
Southern Medical University, China
Target Recruit Count
130
Registration Number
NCT03500848
Locations
🇨🇳

First Affiliated Hospital, Sun Yat-Sen University, Guanzhou, Guangdong, China

🇨🇳

Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China

🇨🇳

Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China

Efficacy and Safety of Rapamycin (Sirolimus) in the Treatment of Symptomatic Uterine Fibroids and Leiomyomatosis

Phase 4
Conditions
Interventions
First Posted Date
2018-04-18
Last Posted Date
2018-04-18
Lead Sponsor
Peking Union Medical College Hospital
Target Recruit Count
25
Registration Number
NCT03500367
Locations
🇨🇳

Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences, Beijing, China/Beiing, China

Comparison of the Efficacy and Safety of Sirolimus Versus Everolimus Versus Mycophenolate in Kidney Transplantation

First Posted Date
2018-03-16
Last Posted Date
2023-04-24
Lead Sponsor
Hospital do Rim e Hipertensão
Target Recruit Count
1209
Registration Number
NCT03468478
Locations
🇧🇷

Hospital do Rim, São Paulo, Sao Paulo, Brazil

Auranofin and Sirolimus in Treating Participants With Ovarian Cancer

First Posted Date
2018-03-07
Last Posted Date
2024-06-24
Lead Sponsor
Mayo Clinic
Target Recruit Count
22
Registration Number
NCT03456700
Locations
🇺🇸

Mayo Clinic, Rochester, Minnesota, United States

SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors

First Posted Date
2018-02-14
Last Posted Date
2023-12-26
Lead Sponsor
Sarcoma Alliance for Research through Collaboration
Target Recruit Count
21
Registration Number
NCT03433183
Locations
🇺🇸

Children's National Medical Center, Washington, District of Columbia, United States

🇺🇸

National Cancer Institute, Bethesda, Maryland, United States

🇺🇸

Johns Hopkins University, Baltimore, Maryland, United States

and more 2 locations

Stem Cell Transplant in Patients With Severe Sickle Cell Disease

First Posted Date
2018-02-05
Last Posted Date
2022-06-28
Lead Sponsor
Kathleen Dorritie
Target Recruit Count
1
Registration Number
NCT03421756
Locations
🇺🇸

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, United States

Rapamycin Treatment for Activated Phosphoinositide 3-Kinase δ Syndrome

First Posted Date
2017-12-26
Last Posted Date
2024-07-09
Lead Sponsor
Children's Hospital of Fudan University
Target Recruit Count
30
Registration Number
NCT03383380
Locations
🇨🇳

Children's Hospital of Fudan University, Shanghai, Shanghai, China

A Pilot-Study of Sirolimus for the Treatment of Systemic Sclerosis

Phase 2
Conditions
Interventions
First Posted Date
2017-12-07
Last Posted Date
2017-12-07
Lead Sponsor
Peking University People's Hospital
Target Recruit Count
72
Registration Number
NCT03365869

Sirolimus Treatment for Refractory PRCA

Phase 4
Completed
Conditions
Interventions
First Posted Date
2017-12-07
Last Posted Date
2021-07-06
Lead Sponsor
Bing Han
Target Recruit Count
64
Registration Number
NCT03364764
Locations
🇨🇳

Peking Union Medical College Hospital, Beijing, Beijing, China

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