Structure of Rapamycin
CAS No.: 53123-88-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Rapamycin is a specific mTOR inhibitor with IC50 of ~0.1 nM.
Synonyms: Sirolimus; AY-22989; D00753
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Leclercq, Gabrielle ; Haegel, Hélène ; Toso, Alberto ; Zimmermann, Tina ; Green, Luke ; Steinhoff, Nathalie , et al.
Abstract: Background: T cell engaging therapies, like chimeric antigen receptor T cells and T cell bispecific antibodies (TCBs), efficiently redirect T cells towards tumor cells, facilitating the formation of a cytotoxic synapse and resulting in subsequent tumor cell killing, a process that is accompanied by the release of cytokines. Despite their promising efficacy in the clinic, treatment with TCBs is associated with a risk of cytokine release syndrome (CRS). The aim of this study was to identify small molecules able to mitigate cytokine release while retaining T cell-mediated tumor killing. Methods: By screening a library of 52 Food and Drug Administration approved kinase inhibitors for their impact on T cell proliferation and cytokine release after CD3 stimulation, we identified mTOR, JAK and Src kinases inhibitors as potential candidates to modulate TCB-mediated cytokine release at pharmacologically active doses. Using an in vitro model of target cell killing by human peripheral blood mononuclear cells, we assessed the effects of mTOR, JAK and Src kinase inhibitors combined with 2+1 T cell bispecific antibodies (TCBs) including CEA-TCB and CD19-TCB on T cell activation, proliferation and target cell killing measured by flow cytometry and cytokine release measured by Luminex. The combination of mTOR, JAK and Src kinase inhibitors together with CD19-TCB was evaluated in vivo in non-tumor bearing stem cell humanized NSG mice in terms of B cell depletion and in a lymphoma patient-derived xenograft (PDX) model in humanized NSG mice in terms of antitumor efficacy. Results: The effect of Src inhibitors differed from those of mTOR and JAK inhibitors with the suppression of CD19-TCB-induced tumor cell lysis in vitro, whereas mTOR and JAK inhibitors primarily affected TCB-mediated cytokine release. Importantly, we confirmed in vivo that Src, JAK and mTOR inhibitors strongly reduced CD19-TCB-induced cytokine release. In humanized NSG mice, continuous treatment with a Src inhibitor prevented CD19-TCB-mediated B cell depletion in contrast to mTOR and JAK inhibitors, which retained CD19-TCB efficacy. Ultimately, transient treatment with Src, mTOR and JAK inhibitors minimally interfered with antitumor efficacy in a lymphoma PDX model. Conclusions: Taken together, these data support further evaluation of the use of Src, JAK and mTOR inhibitors as prophylactic treatment to prevent occurrence of CRS.
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Purchased from AmBeed: 159351-69-6 ; 941678-49-5 ; 302962-49-8 ; 162635-04-3 ; 53123-88-9
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Leclercq, Gabrielle ;
Abstract: T cell bispecific antibodies (TCBs) are a novel class of T cell engagers redirecting T cells towards tumor cells, facilitating the formation of a cytotoxic synapse and resulting in tumor celllysis. On-target activity of TCBs may come with a risk of Cytokine Release Syndrome (CRS), characterized by elevated levels of pro-inflammatory cytokines in the serum, such as IL-6, IL-1β, TNF-α or IFN-γ and over activation of immune cells. Besides, the expression of the tumorassociated antigen on healthy cells may induce off-tumor activity of the TCB and contribute to inflammation. Despite the use of step-up dosing, glucocorticoids, or tocilizumab to manage or prevent these safety liabilities, they remain the major dose-limiting toxicities associated with the treatment of T cell engagers, highlighting the need to develop preventive mitigation treatments. To this aim, we investigated the biological mechanisms and the chronology of events involved in TCB-mediated cytokine release and explored mitigation strategies that might retain profound treatment efficacy while reducing cytokine release. Using an in vitro co-culture of peripheral blood mononuclear cells (PBMCs) or total leukocytes(PBMCs + neutrophils) and target cells with the respective TCBs, or whole blood treated with a B cell depleting TCB, we confirmed the contribution of T cell and myeloid cells and revealed the role of neutrophils in the TCB-mediated cytokine release. In the same model, the use of anticytokine neutralizing antibodies provided insights into the chronology of events triggering the cascade of cytokines after TCB stimulation. Ultimately this work guided the evaluation of mitigation strategies directed against T-cell derived cytokine release by targeting kinases involved in signaling pathways downstream of the T cell receptor (TCR) after stimulation with TCBs. A novel small molecule-kinase inhibitors screen identified mTOR, JAK and Src inhibitors as candidates to switch-off T-cell derived cytokine release. We validated the effects of these kinase inhibitors and fine-tuned their effective doses in in vitro co-cultures of peripheral blood mononuclear cells (PBMCs) and tumor cells with the respective TCBs. In vivo, we used nontumor or tumor-bearing-humanized NSG mice to assess the effect of mTOR, JAK and Srcinhibitors on CD19-TCB-mediated cytokine release and anti-tumor efficacy. Altogether, we confirmed the biological mechanisms of the TCB-mediated cytokine cascade and revealed the contribution of neutrophils. Our work on kinase inhibitors highlights their differential activities on the inhibition of cytokine release and/or T cell cytotoxicity and demonstrates the decoupling between both mechanisms. Our data open new horizons for the prophylactic mitigation of CRS with the use of FDA approved mTOR and JAK inhibitors or the transient use of the Src inhibitor dasatinib. Finally, our results also indicate that dasatinib may serve as an “antidote” against adverse events related to the treatment with TCBs such as high grade CRS or unpredictable off-tumor activity of TCBs, a strategy which is now implemented the clinic.
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Purchased from AmBeed: 302962-49-8 ; 943319-70-8 ; 162635-04-3 ; 53123-88-9 ; 380843-75-4
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CAS No. : | 53123-88-9 |
Formula : | C51H79NO13 |
M.W : | 914.17 |
SMILES Code : | O=C(C([C@](O[C@]1([H])C[C@@H](/C(C)=C/C=C/C=C/[C@H]2C)OC)([C@@H](CC1)C)O)=O)N(CCCC3)[C@]3([H])C(O[C@](CC([C@@H](/C=C([C@H]([C@H](C([C@H](C)C2)=O)OC)O)\C)C)=O)([H])[C@H](C)C[C@H](CC[C@H]4O)C[C@H]4OC)=O |
Synonyms : |
Sirolimus; AY-22989; D00753
|
MDL No. : | MFCD00867594 |
InChI Key : | QFJCIRLUMZQUOT-HPLJOQBZSA-N |
Pubchem ID : | 5284616 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Target |
|
In Vitro:
Concentration | Treated Time | Description | References |
C2C12 cells | 100 nM | PMC9675748 | ||
F98 astrocytoma cells | 100 nM | 24 h | To investigate the cytoprotective effect of rapamycin against GO-induced apoptosis. | PMC7081710 |
Primary articular chondrocytes | 0, 1, 5, 10, 20 nM | 2 days | to assess cell viability. | PMC10548624 |
Drosophila S2 cells | 100 nM | 2 h | To examine translational activity at the whole-transcriptome level by ribosome profiling. | PMC7423359 |
MSCs | 50 nM | improved colony-forming capability, proliferation, and osteogenic differentiation of TNFα−/− MSCs | PMC7775432 | |
MDMs | 10 nM | 24 h | To investigate the effect of metabolic reprogramming on cytokine production. | PMC7210971 |
yeast cells | 200 nM | 1.5 h | To study the upregulation of RPACs and the effects on proteasome assembly under TORC1 inhibition. | PMC9276530 |
CHO-Gal4 cells | 0 or 50 nM | 12 h | TF clustering directly enhances transcriptional activation and amplifies target gene expression. | PMC9106659 |
yeast cells | 1 ng/ul | 1 h | induce CICI formation | PMC8828778 |
HL60 and U937 cells | 500 mg/mL | 24 h | To evaluate the cytokine profiles and elimination capacity of CAR-T cells; rapamycin-pretreated exhibited lower AML residues. | PMC9401534 |
MLE-12 cells | 10 μg/ml | 24 h | To explore the effect of autophagy activation with rapamycin treatment on SWCNTs-induced senescence and FMT in MLE-12 cells. | PMC9970859 |
HeLa | 1 μM | 80 min | To study the effects of rapamycin on immunostaining in HeLa cells expressing a specific construct. | PMC9715632 |
COS-7 cells | 100 nM | 50 min | The purpose was to evaluate the effect of rapamycin on mitochondrial deformation, resulting in a ~60% decrease in TMRE signal. | PMC9338259 |
SCC-25 cells | 200 nM | up to 18 h | To induce autophagy and assess its effect on FN1 degradation, showing that increased autophagic activity correlates with reduced FN1 levels. | PMC7736930 |
Raw264.7 cells | 10 µM | 2 h | To evaluate the role of mTOR in BSNP-induced trained immunity, assessing inflammatory cytokine expression and phagocytosis. | PMC8692910 |
CD25+ cells | 100 ng/ml | days 4, 7, 11 and 18 | To facilitate ex vivo CD25+ cell expansion. | PMC9763232 |
MEFs | 5 μmol | 3 h | To induce autophagy and analyze LC3B expression. | PMC8787410 |
HEK293T | 333 nM | Disruption of FUS condensates and prevention of new condensate formation. | PMC7985322 | |
Tsc2-deficient cells | 20 nM | Had no additional effect on the proliferation of Tsc2-deficient cells, but decreased the expression of Tfeb by about 2-fold. | PMC8275687 | |
yeast cells | 1 µM | 5 min | disruption of mismatch repair | PMC8450099 |
Human Renal Proximal Tubular Cells | 100 nM | 24 h | To investigate the effect of rapamycin on GLUT2 expression under hyperglycemic conditions. | PMC8980033 |
Intestinal Intraepithelial Lymphocytes (IEL) | 20 nM | specified amount of time in figures | To assess the impact of Rapamycin on IEL growth and granzyme B expression. | PMC8277781 |
Huh7 cells | 20 nM | 24 h | To monitor autophagic flux as a positive control and its effects. | PMC8350071 |
DLD1 cells | 100 ng/ml | 2 h | to drive chemically induced dimerisation of TEV, and, as a result, PKCε cleavage | PMC7070073 |
RPE cells | 100 nM | 24 h | To determine optimal drug concentration and its time-dependent response; no significant difference was observed comparing treatments to no treatment controls. | PMC7327959 |
Myotubes cells | 10 nM | 24 h | To investigate mTORC1 activity suppression and measure autophagic flux. | PMC7481251 |
Nalm6 and 697 cells | 10-20 μM | 2 days | Combination treatment showed synergistic cytotoxic effects. | PMC8102195 |
OP9-DL1 cultures | 0, 1, 10, 100, or 1000 nM | PMC9537144 | ||
Endothelial cells and smooth muscle cells | 0.3 to 3000 ng/mL | 24 h, 48 h, 72 h | To compare anti-proliferative effects of SRM-NPs and PTX-NPs; SRM proved more effective under hypoxia. | PMC7530254 |
CD8+ T cells | 20 nM | 36 h | Transient mTOR inhibition can restore ACD in aged CD8+ T cells, suggesting a potential therapeutic strategy to reinvigorate immune responses in elderly individuals. | PMC8113513 |
In Vivo:
Administration | Dosage | Frequency | Description | References |
C57BL/6 mice | DMM surgery model for OA | Intra-articular injection | 10 µM | once weekly for 8 weeks | to evaluate the therapeutic effect on OA and reduce cartilage destruction. | PMC10548624 |
SCID/NOD mice | tumor-bearing mice | Intraperitoneal injection | 6 mg/kg | daily | Combination treatment to enhance efficacy against tumors. | PMC9426012 |
BALB/c nude mice | HepG2 cells or MHCC97H cells transplantation | Intraperitoneal injection | 3 mg/kg | every other day starting at day 4 | Rescues increased cell size and mTORC1 activation induced by TET2 deficiency. | PMC10406918 |
Mice | DTG mice | Intraperitoneal injection | 4 mg/kg | daily for 5 consecutive days | improved symptoms for human patients with extramammary PD. | PMC7608215 |
Mice | Pik3c2b KO Mouse Model | Intraperitoneal injection | 10 mg/kg | Single treatment before sacrifice | To normalize mTORC1 activity in KO adult brains. | PMC9337808 |
Mice | Telomerase-deficient mice | Intraperitoneal injection | 2 mg/kg | 2 h post-injection | To test the inhibition of mTORC1 and understand its role in the survival of telomerase-deficient mice. | PMC7054554 |
Mice | OTULIN-deficient mouse model | Intraperitoneal injection | 1 mg/kg | Twice weekly from postnatal day 8 until 8 weeks of age | To reduce liver pathology caused by OTULIN deficiency; rapamycin treatment reduced histological abnormalities and fibrosis. | PMC7206033 |
NRG mice | patient-derived xenografts (PDX) | Intraperitoneal injection | 4 mg/kg | 5 days/week | Combination treatment significantly prolonged survival of mice. | PMC8102195 |
Mice | Pancreatic growth model | Intraperitoneal injection | 0.2 mg/(100 g body weight) | Daily injections for 7 days | To study the role of the mTOR signaling pathway in pancreatic growth, results showed that rapamycin inhibited camostat-induced pancreatic growth | PMC1779746 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT06257420 | Myalgic Encephalomyelitis|Long... More >>-COVID Less << | ENROLLING_BY_INVITATION | 2026-06-11 | Center For Complex Diseases, P... More >>alo Alto, California, 94040, United States|The Mayo Clinic, Rochester, Minnesota, 55905, United States|Sierra Internal Medicine, Incline Village, Nevada, 89451, United States|Bateman Horne Center, Salt Lake City, Utah, 84102, United States|Center For Complex Diseases, Seattle, Washington, 98109, United States Less << | |
NCT00275522 | Kidney Transplant | PHASE4 | COMPLETED | 2025-12-07 | Mayo Clinic, Rochester, Minnes... More >>ota, 55905, United States Less << |
NCT00040508 | Focal Glomerulosclerosis | PHASE2 | COMPLETED | 2025-01-05 | National Institute of Diabetes... More >> and Digestive and Kidney Diseases (NIDDK), Bethesda, Maryland, 20892, United States Less << |
NCT00195481 | Kidney Failure|Graft vs Host D... More >>isease Less << | PHASE4 | COMPLETED | 2025-12-05 | Bangalore, Karnataka, 566 006,... More >> India|Bangalore, Karnataka, 566 018, India|Saket, South Delhi, India|Chennai, Tamil Nadu, 600 004, India|New Delhi, India Less << |
NCT04775173 | Kaposiform Hemangioendotheliom... More >>a Less << | PHASE2 | COMPLETED | 2023-08-10 | West China Hospital of Sichuan... More >> University, Chengdu, Sichuan, 610041, China Less << |
NCT00223678 | Kidney Transplant | PHASE4 | COMPLETED | 2025-10-09 | Vanderbilt University, Nashvil... More >>le, Tennessee, 37232, United States Less << |
NCT01811667 | Cardiovascular Abnormalities | PHASE3 | COMPLETED | 2025-01-16 | Cliniques universitaires Saint... More >>-Luc, Brussels, 1200, Belgium Less << |
NCT01709136 | Hypertension | PHASE2|PHASE3 | TERMINATED | 2025-01-10 | - |
NCT04598815 | Graves Ophthalmopathy | PHASE2 | NOT_YET_RECRUITING | 2025-05-31 | Ospedale Cisanello-Endocrinolo... More >>gy II, Pisa, 56124, Italy Less << |
NCT03150914 | LAM|Lymphangioleiomyomatosis | PHASE3 | ACTIVE_NOT_RECRUITING | 2025-06-30 | Stanford University, Palo Alto... More >>, California, 94305, United States|National Jewish Hospital, Denver, Colorado, 80206-2761, United States|Emory University, Atlanta, Georgia, 30322, United States|Loyola University, Chicago, Illinois, 60153, United States|Brigham and Woman's Hospital, Boston, Massachusetts, 20892, United States|University of Cincinnati, Cincinnati, Ohio, 45174, United States|University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States|Swedish Health, Seattle, Washington, 98104, United States Less << |
NCT02117596 | Renal Transplant | COMPLETED | 2025-11-12 | Pediatric Nephrology of Alabam... More >>a, Birmingham, Alabama, 35205, United States|UCLA, Los Angeles, California, 90095, United States|Stanford University, Stanford, California, 94305, United States|Emory University, Atlanta, Georgia, United States Less << | |
NCT00876434 | Anterior Uveitis | PHASE1 | COMPLETED | 2011-02-10 | National Institutes of Health ... More >>Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Less << |
NCT02365415 | Peripheral Pulmonary Stenosis|... More >>In-stent Stenosis Less << | PHASE2 | WITHDRAWN | 2025-04-18 | Boston Children's Hospital, Bo... More >>ston, Massachusetts, 02115, United States Less << |
NCT05324384 | Hemangioendothelioma | PHASE2 | RECRUITING | 2025-11-30 | West China Hospital of Sichuan... More >> University, Chengdu, Sichuan, 610041, China Less << |
NCT04461340 | COVID 19 | PHASE2 | UNKNOWN | 2020-11-30 | Faculty of Medicine, Alexandri... More >>a university, Egypt, Alexandria, 21526, Egypt Less << |
NCT05386914 | Genetic Predisposition to Dise... More >>ase|Healthy Volunteers Less << | PHASE1 | RECRUITING | 2025-12-27 | University of Missouri-Columbi... More >>a, Columbia, Missouri, 65212, United States Less << |
NCT00282217 | Kidney Failure|Kidney Diseases | PHASE4 | COMPLETED | - | Albacete, 2006, Spain|Barcelon... More >>a, 8035, Spain|Cadiz, 11009, Spain|Granada, 18014, Spain|L'Hospitalet de Llobregat, 8701, Spain|La Coruna, 15006, Spain|Madrid, 28034, Spain|Madrid, 28035, Spain|Madrid, 28040, Spain|Malaga, 29010, Spain|Oviedo, 33006, Spain|Sevilla, 41013, Spain|Zaragoza, 50009, Spain Less << |
NCT05425056 | Complication of Renal Dialysis... More >>|End Stage Renal Disease|End Stage Kidney Disease|ESRD|Chronic Kidney Failure|Complication of Hemodialysis|Vascular Access Complication|Arteriovenous Fistula Less << | PHASE3 | ACTIVE_NOT_RECRUITING | 2025-08-25 | Veterans Affairs San Diego Hea... More >>lth Center, San Diego, California, 92161, United States|Lundquist Institute for Biomedical Innovation, Torrance, California, 90502, United States|MedStar Cardiovascular Research Network at MedStar Washington Hospital Center, Washington, District of Columbia, 20010, United States|American Access Care of Miami, Miami, Florida, 33156, United States|Emory University Hospital Midtown, Atlanta, Georgia, 30308, United States|Augusta University, Augusta, Georgia, 30912, United States|University of Louisville, Louisville, Kentucky, 40202, United States|The Brigham and Women's Hospital, Boston, Massachusetts, 02115, United States|Mount Sinai Hospital, New York, New York, 10029, United States|Atrium Health, Charlotte, North Carolina, 28204, United States|Surgical Specialists of Charlotte, Charlotte, North Carolina, 28207, United States|The Regional Medical Center/Dialysis Access Institute, Orangeburg, South Carolina, 29118, United States|James Eric Gardner, MD PC, Memphis, Tennessee, 38115, United States|Arteries & Veins, El Paso, Texas, 79912, United States|Houston Methodist, Houston, Texas, 77030, United States|Houston Methodist, Sugar Land, Texas, 77479, United States|Sentara Norfolk General Hospital/Sentara Health Research Center, Norfolk, Virginia, 23507, United States|University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom|St Helier Hospital, Carshalton, SM5 1AA, United Kingdom|NHS Greater Glasgow and Clyde, Glasgow, United Kingdom|Barts Health NHS Trust of Royal London Hospital, London, United Kingdom|St George's University Hospitals NHS Foundation Trust, London, United Kingdom Less << |
NCT00711490 | Diabetic Retinopathy | PHASE1|PHASE2 | COMPLETED | 2025-01-11 | National Institutes of Health ... More >>Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Less << |
NCT02440789 | HIV-1 Infection | PHASE1|PHASE2 | COMPLETED | 2018-02-01 | 801 University of California, ... More >>San Francisco HIV/AIDS CRS, San Francisco, California, 94110, United States|Whitman Walker Health CRS (31791), Washington, District of Columbia, 20005, United States|Univ. of Miami AIDS CRS (901), Miami, Florida, 33136, United States|The Ponce de Leon Center CRS (5802), Atlanta, Georgia, 30308, United States|Washington University CRS (2101), Saint Louis, Missouri, 63110, United States|Weill Cornell Uptown CRS (7803), New York, New York, 10011, United States|31787 University of Rochester Adult HIV Therapeutic Strategies Network CRS, Rochester, New York, 14642, United States|Univ. of Cincinnati CRS (2401), Cincinnati, Ohio, 45267, United States|Houston AIDS Research Team CRS (31473), Houston, Texas, 77030, United States|University of Washington AIDS CRS (1401), Seattle, Washington, 98104, United States Less << |
NCT00189202 | End Stage Renal Disease|Kidney... More >> Transplantation Less << | PHASE2|PHASE3 | COMPLETED | 2008-07-01 | University of Michigan Health ... More >>Center, Ann Arbor, Michigan, 48109, United States Less << |
NCT00409994 | Rectum Cancer | PHASE1|PHASE2 | COMPLETED | 2025-12-18 | Maastricht Radiation Oncology,... More >> Maastricht, Limburg, 6202 AZ, Netherlands Less << |
NCT02296749 | Healthy | PHASE1 | COMPLETED | 2025-02-10 | Bioserve Clinical Research Pvt... More >>. Ltd, Balanagar, Hyderabad, Andhra Pradesh, 500 037, India Less << |
NCT01658007 | Relapsed Lymphoblastic Leukemi... More >>a|Recurrent Adult Lymphoblastic Lymphoma|Refractory Acute Lymphoblastic Leukemia|Refractory Lymphoblastic Lymphoma Less << | EARLY_PHASE1 | TERMINATED | 2025-01-17 | Cincinnati Children's Hospital... More >> Medical Center, Cincinnati, Ohio, 45229, United States Less << |
NCT00050713 | Membranous Glomerulonephritis|... More >>Lupus Membranous Nepropathy Less << | PHASE2 | COMPLETED | 2007-08-27 | National Institutes of Health ... More >>Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Less << |
NCT04892212 | Lupus Nephritis|Immunosuppress... More >>ion|Effect of Drug Less << | PHASE2|PHASE3 | UNKNOWN | 2023-10-30 | - |
NCT02524639 | Hyperinsulinism | PHASE1|PHASE2 | WITHDRAWN | 2018-05-29 | The Children's Hospital of Phi... More >>ladelphia, Philadelphia, Pennsylvania, 19104, United States Less << |
NCT02443818 | Segmental Overgrowth Disorders... More >> Due to PIK3CA Less << | PHASE2 | COMPLETED | 2025-11-16 | CHU d'Angers, Angers, 49933, F... More >>rance|CHU de Bordeaux - GH Pellegrin, Bordeaux, 33076, France|CHU de DIJON, Dijon, 21079, France|H?pital Jeanne de Flandre, Lille, 59037, France|CHRU de Montpellier - H?pital Saint-Eloi, Montpellier, 34295, France|Hopitaux de Brabois Chu Nancy, Nancy, 54511, France|H?pital mère-enfant de Nantes, Nantes, 44093, France|CHU Paris - Necker, Paris, 75015, France|HCL Lyon - CH Lyon Sud, Pierre-Bénite, 69495, France|P?le Cardiovasculaire et Métabolique - H?pital Larrey, Toulouse, 31059, France|CHRU de Tours, Tours, 37044, France Less << |
NCT06236022 | Dilated Cardiomyopathy|Kaposi'... More >>s Sarcoma-Associated Herpesvirus Infection Less << | PHASE4 | RECRUITING | 2028-12-31 | Tongji Hospital, Wuhan, Hubei,... More >> 430030, China Less << |
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NCT01649960 | Aging|CAD | PHASE1 | COMPLETED | 2025-12-15 | Mayo Clinic in Rochester and M... More >>ayo Health System sites in Austin and Albert Lea, Minnesota, Rochester, Minnesota, 55905, United States Less << |
NCT03161340 | Recurrent Implantation Failure | PHASE2 | COMPLETED | 2018-06-20 | Qom ACECR ART Center, Qom, Ira... More >>n, Islamic Republic of|Estern Azarbaijan ACECR ART center, Tabriz, Iran, Islamic Republic of Less << |
NCT06308445 | Familial Adenomatous Polyposis | PHASE2 | NOT_YET_RECRUITING | 2025-08-30 | CHU Bordeaux H?pital Pellegrin... More >>, Bordeaux, 33076, France|CHU Montpellier H?pital Arnaud de Villeneuve, Montpellier, 34295, France|APHP H?pital Robert Debré, Paris, 75019, France|CHU Toulouse H?pital des Enfants, Toulouse, 31300, France Less << |
NCT03933904 | Castleman Disease|Castleman's ... More >>Disease, Multicentric Less << | PHASE2 | ACTIVE_NOT_RECRUITING | 2025-06-30 | University of Arkansas for Med... More >>ical Sciences, Little Rock, Arkansas, 72205, United States|University of California - San Diego, La Jolla, California, 92093, United States|Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, United States|University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States Less << |
NCT00195195 | Transplantation | COMPLETED | 2025-06-08 | Gothenburg, SE-413 45, Sweden|... More >>Stockholm, SE-141 86, Sweden|Uppsala, SE-751 85, Sweden Less << | |
NCT00634270 | Neurofibromatosis Type 1 | PHASE2 | COMPLETED | 2025-12-15 | The University of Alabama at B... More >>irmingham, Birmingham, Alabama, 35294, United States|Children's National Medical Center, Washington, D.C., District of Columbia, 20010, United States|University of Chicago, Chicago, Illinois, 60637, United States|National Cancer Institute (NCI), Bethesda, Maryland, 20892, United States|Children's Hospital Boston, Boston, Massachusetts, 02115, United States|Washington University, Saint Louis, Missouri, 63110, United States|Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229-4006, United States|Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19096, United States|University of Utah, Salt Lake City, Utah, 84132, United States Less << |
NCT03662412 | Pancreatic Cancer | PHASE1|PHASE2 | UNKNOWN | 2023-06-30 | The second affiliated hospital... More >> of Zhejiang University, Hangzhou, Zhejiang, 310009, China Less << |
NCT01265030 | Desmoid Tumor | PHASE1|PHASE2 | COMPLETED | 2021-12-22 | UCLA Medical Center, Los Angel... More >>es, California, 90095, United States|Rady Children's Hospital, San Diego, California, 92123, United States|University of Florida College of Medicine, Gainesville, Florida, 32611, United States|Maine Medical Center, Portland, Maine, 04102, United States|University of Minnesota, Minneapolis, Minnesota, 55455, United States|Children's Mercy Hospital, Kansas City, Missouri, 64108, United States|Seattle Children's Hospital, Seattle, Washington, 98101, United States|Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, United States Less << |
NCT00266123 | Graft Rejection|Kidney Failure... More >>|Kidney Transplant Less << | PHASE4 | COMPLETED | 2025-07-07 | - |
NCT02509468 | Vascular Malformation | PHASE2 | COMPLETED | 2025-03-19 | Service de dermatologie, CHU A... More >>ngers, Angers, 49933, France|Service de dermatologie, H?pital du Bocage, CHU Dijon, Dijon, 21079, France|Explorations Médecine Vasculaire H?pital A. Michallon, CHU de Grenoble, Grenoble, 38700, France|Service de radiologie H?pital Femme-Mère-Enfant, Hospices Civils de Lyon, Lyon, 69000, France|Service de Dermatologie, vénéréologie et cancérologie cutanée, H?pital La Timone APHM, Marseille, 13000, France|Service de Dermatologie, H?pital St Eloi, CHU Montpellier, Montpellier, 34000, France|Service de Dermatologie, H?pital H?tel-Dieu, CHU Nantes, Nantes, 44000, France|Service de dermatologie, CHU Nice, Nice, 06202, France|Service de dermatologie, APHP Necker, Paris, 75743, France|Service de Dermatologie, H?pital Pontchaillou, CHU RENNES, Rennes, 35000, France|Service de dermatologie, H?pital Larrey, CHU Toulouse, Toulouse, 31059, France|Consultations externes de Dermatologie, H?pital Clocheville, CHU Tours, Tours, 37000, France Less << |
NCT02638389 | Vascular Malformations | PHASE3 | RECRUITING | 2030-04-01 | Cliniques Universitaires Saint... More >>-Luc, Université Catholique de Louvain Bruxelles, Bruxelles, Région De Bruxelles-Capitale, 1200, Belgium|CHU Caen, Caen, Bretagne, 14000, France|Universit?tsklinikum Freiburg, Freiburg, 79106, Germany Less << |
NCT05746689 | IgG4-related Disease | NOT_YET_RECRUITING | 2028-12-31 | - | |
NCT04861064 | Venous Malformation|Lymphatic ... More >>Malformation Less << | PHASE2 | RECRUITING | 2025-06-25 | Medical University of South Ca... More >>rolina, Charleston, South Carolina, 29403, United States Less << |
NCT02753309 | Bladder Cancer | EARLY_PHASE1 | COMPLETED | 2021-03-02 | University of Texas Health Sci... More >>ence Center at San Antonio, San Antonio, Texas, 78229, United States Less << |
NCT04448873 | Kaposiform Hemangioendotheliom... More >>a|Kasabach-Merritt Syndrome Less << | PHASE4 | COMPLETED | 2023-07-01 | Children's Hospital of Fudan U... More >>niversity, Shanghai, Shanghai, 210012, China Less << |
NCT03688191 | Connective Tissue Diseases|Thr... More >>ombocytopenia Less << | PHASE4 | UNKNOWN | 2019-09-30 | Peking Union Medical College H... More >>ospital, Beijing, Beijing, 100005, China Less << |
NCT05237687 | Aging | PHASE2 | RECRUITING | 2025-11-25 | UT Southwestern Medical Center... More >>, Dallas, Texas, 75390, United States Less << |
NCT00306397 | Kidney Transplantation | PHASE4 | COMPLETED | 2025-12-08 | University Hospital Basel, Cli... More >>nic for Transplantation Immunology and Nephrology, Basel, 4031, Switzerland Less << |
NCT06563817 | Communicating Hydrocephalus|Ce... More >>rebral Intraventricular Hemorrhage|Secondary Normal Pressure Hydrocephalus|Post Hemorrhagic Hydrocephalus Less << | PHASE2 | RECRUITING | 2025-07-25 | Beijing Tiantan Hospital, Capi... More >>tal Medical University, Beijing, Beijing, 100070, China Less << |
NCT00811915 | Kidney Transplantation | PHASE3 | COMPLETED | 2025-06-14 | UHAmiens, Amiens, France|UHAng... More >>ers, Angers, 49933, France|UHCaen, Caen, 14000, France|UHLimoges, Limoges, France|UHNecker, Paris, 75015, France|UHRennes, Rennes, 35000, France|UHRouen, Rouen, 76000, France|UHTours, Tours, France Less << |
NCT06550271 | Aging | COMPLETED | 2023-12-15 | AgelessRx, Ann Arbor, Michigan... More >>, 48104, United States Less << | |
NCT03583307 | Vascular Anomaly | COMPLETED | 2021-02-19 | West China Hospital of Sichuan... More >> University, Chengdu, Sichuan, 61004·, China Less << | |
NCT00470665 | Renal Allograft Recipients | PHASE3 | COMPLETED | 2025-07-04 | - |
NCT04094675 | PTEN Gene Mutation|PTEN Hamart... More >>oma Tumor Syndrome|PTEN Hamartoma Syndrome|Cowden Syndrome|Bannayan Syndrome|Bannayan Zonana Syndrome|Polyposis Less << | PHASE2 | ACTIVE_NOT_RECRUITING | 2025-02-25 | The Ohio State University Wexn... More >>er Medical Center, Columbus, Ohio, 43210, United States Less << |
NCT05269849 | Hereditary Hemorrhagic Telangi... More >>ectasia|Nosebleeds|Epistaxis Less << | PHASE2 | ACTIVE_NOT_RECRUITING | 2025-02-10 | St. Michael's Hospital, Toront... More >>o, Ontario, M5B 1W8, Canada Less << |
NCT00305396 | Kidney Transplantation | PHASE4 | COMPLETED | 2025-03-05 | Vanderbilt University Medical ... More >>Center/Nashville VA, Nashville, Tennessee, 37232, United States Less << |
NCT04948203 | Pulmonary Fibrosis|COVID-19 Pn... More >>eumonia|Long COVID Less << | PHASE2|PHASE3 | RECRUITING | 2025-12-25 | University of Chicago, Chicago... More >>, Illinois, 60637, United States Less << |
NCT03781050 | Peutz-Jeghers Syndrome | PHASE4 | UNKNOWN | 2022-07-01 | Peking Union Medical College H... More >>ospital, Chinese Academy of Medicine Sciences, Beijing, China/Beijing, 100000, China Less << |
NCT01236378 | Transplant Rejection|Renal Tra... More >>nsplantation Less << | PHASE1 | COMPLETED | 2025-04-11 | Pfizer Investigational Site, C... More >>hongqing, 400038, China|Pfizer Investigational Site, Shanghai, 200127, China Less << |
NCT00328770 | Liver Carcinoma | PHASE2|PHASE3 | COMPLETED | 2025-03-06 | University of Alberta, Edmonto... More >>n, Alberta, T6G 2B7, Canada Less << |
NCT00044720 | Chronic Kidney Failure|Graft v... More >>s Host Disease|Kidney Transplantation Less << | PHASE4 | COMPLETED | 2025-07-05 | - |
NCT01827618 | Invasive Bladder Cancer Stage ... More >>II Less << | EARLY_PHASE1 | COMPLETED | 2025-04-14 | UT Health Science Center San A... More >>ntonio, San Antonio, Texas, 78229, United States Less << |
NCT02062944 | Acute Rejection of Liver Trans... More >>plant|Effects of Immunosuppressant Therapy Less << | COMPLETED | 2025-07-20 | Northwestern University, Chica... More >>go, Illinois, 60611, United States Less << | |
NCT00254709 | Kidney Failure|Graft Rejection... More >>|Aged Less << | PHASE4 | COMPLETED | 2025-09-05 | - |
NCT01632605 | ADPKD | COMPLETED | 2025-04-12 | Division of Nephrology and Dia... More >>lysis, Department of Medicine III, Medical University Vienna, Vienna, 1090, Austria Less << | |
NCT06022068 | Alzheimer Disease | PHASE1|PHASE2 | ENROLLING_BY_INVITATION | 2025-01-31 | Karolinska University Hospital... More >> Memory clinic, Solna, Stockholm, 171 64, Sweden Less << |
NCT03047980 | Sturge-Weber Syndrome | PHASE2|PHASE3 | COMPLETED | 2020-10-27 | Kennedy Krieger Institute, Bal... More >>timore, Maryland, 21205, United States|Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229, United States Less << |
NCT00779194 | Systemic Lupus Erythematosus (... More >>SLE) Less << | PHASE2 | COMPLETED | 2015-12-16 | SUNY Upstate Medical Universit... More >>y, Syracuse, New York, 13210, United States Less << |
NCT02428296 | PIK3CA-Related Overgrowth Spec... More >>trum (PROS)|Growth Disorder|Genetics Less << | PHASE2 | COMPLETED | 2018-02-14 | National Institutes of Health ... More >>Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Less << |
NCT01680250 | Polycystic Kidney Diseases | PHASE2|PHASE3 | UNKNOWN | 2025-08-15 | Seoul National University Hosp... More >>ital, Seoul, 110-744, Korea, Republic of Less << |
NCT03383380 | Activated PI3K-delta Syndrome|... More >>Immunodeficiency Primary Less << | PHASE1|PHASE2 | COMPLETED | 2023-11-30 | Children's Hospital of Fudan U... More >>niversity, Shanghai, Shanghai, 201102, China|Children's Hospital of Fudan University, Shanghai, Shanghai, China Less << |
NCT04200911 | Cognitive Impairment, Mild|Alz... More >>heimer Disease Less << | EARLY_PHASE1 | COMPLETED | 2022-01-13 | UTHSA McDermott Clinical Scien... More >>ces Building, San Antonio, Texas, 78229, United States Less << |
NCT06719791 | Epilepsy, Drug Resistant | EARLY_PHASE1 | RECRUITING | 2028-12-01 | Xuanwu Hospital, Beijing, Chin... More >>a Less << |
NCT02177760 | Severe Combined Immunodeficien... More >>cy|Transplacental Maternal Engraftment|Stem Cell Transplant Less << | PHASE2 | WITHDRAWN | 2025-11-15 | Benioff Children's Hospital at... More >> UCSF Medical Center, San Francisco, California, 94143, United States Less << |
NCT00555373 | Renal Transplant | COMPLETED | 2025-11-12 | Pediatric Nephrology of Alabam... More >>a, Birmingham, Alabama, 35205, United States|UCLA, Los Angeles, California, 90095, United States|Stanford University, Stanford, California, 94305, United States|Emory University, Atlanta, Georgia, United States Less << | |
NCT01764607 | Squamous Cell Skin Carcinoma | PHASE2 | TERMINATED | 2025-06-14 | Shands at the University of Fl... More >>orida, Gainesville, Florida, 32610, United States Less << |
NCT00141804 | Kidney Transplantation | PHASE3 | UNKNOWN | 2025-06-05 | University Hospital Muenster, ... More >>Muenster, 48149, Germany Less << |
NCT03103893 | Dermal Atrophy | PHASE1|PHASE2 | COMPLETED | 2017-11-30 | Drexel Dermatology, Philadelph... More >>ia, Pennsylvania, 19102-1101, United States Less << |
NCT00170053 | Kidney Diseases | PHASE1 | COMPLETED | 2025-09-08 | Mayo Clinic, Jacksonville, Flo... More >>rida, 32224, United States Less << |
NCT06261060 | Familial Platelet Disorder|Hem... More >>atopoietic Less << | PHASE2 | RECRUITING | 2028-06-11 | MD Anderson Cancer Center, Hou... More >>ston, Texas, 77030, United States Less << |
NCT01517074 | Scleritis | PHASE1|PHASE2 | COMPLETED | 2025-04-14 | National Institutes of Health ... More >>Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Less << |
NCT00697112 | Renal Transplantation | COMPLETED | 2025-12-12 | Pfizer Investigational Site, C... More >>aba, Buenos Aires, 1425, Argentina|Pfizer Investigational Site, Caba, Buenos Aires, C1093AAS, Argentina|Pfizer Investigational Site, Caba, Buenos Aires, C1181ACH, Argentina|Pfizer Investigational Site, Caba, Buenos Aires, Argentina|Pfizer Investigational Site, Barrio General Paz, Cordoba, 5016, Argentina|Pfizer Investigational Site, Cordoba, 5016, Argentina|Pfizer Investigational Site, Santa Fe, 3000, Argentina|Pfizer Investigational Site, Tucuman, 4000, Argentina Less << | |
NCT00126672 | Nonmalignant Neoplasm|Tuberous... More >> Sclerosis|Lymphangioleimyomatosis|Kidney Angiomyolipoma Less << | PHASE2 | COMPLETED | 2025-04-10 | Loma Linda University School o... More >>f Medicine, Loma Linda, California, 92350, United States|Connecticut Children's Medical Center, Hartford, Connecticut, 06106, United States|Massachusetts General Hospital, Boston, Massachusetts, 02114, United States|New York University Medical Center, New York, New York, 10016, United States|Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229-3039, United States|University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, United States|University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75390, United States Less << |
NCT04707209 | Retinal Astrocytic Hamartoma | COMPLETED | 2024-03-22 | The Hospital for Sick Children... More >>, Toronto, Ontario, M5G1X8, Canada Less << | |
NCT05458492 | Sarcoidosis|Cutaneous Sarcoido... More >>sis Less << | PHASE2 | NOT_YET_RECRUITING | 2025-05-27 | - |
NCT03942926 | Plastic Bronchitis | PHASE2 | UNKNOWN | 2020-05-05 | Peking Union Medical College H... More >>ospital, Beijing, Beijing, 100730, China Less << |
NCT02642094 | Cancer of Breast | PHASE2 | TERMINATED | 2022-05-01 | University of Texas Health Sci... More >>ence Center San Antonio, San Antonio, Texas, 78229, United States Less << |
NCT01195922 | Mouth Neoplasms|Head and Neck ... More >>Neoplasms|Tongue Neoplasms|Carcinoma, Squamous Cell Less << | PHASE1|PHASE2 | COMPLETED | 2025-12-15 | National Institutes of Health ... More >>Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Less << |
NCT02724332 | Hepatocellular Carcinoma|Rapam... More >>ycin Less << | PHASE1 | COMPLETED | 2025-12-15 | Eastern hepatobilliary surgery... More >> hospital, Shanghai, Shanghai, 200438, China Less << |
NCT05549167 | Juvenile Nasopharyngeal Angiof... More >>ibroma Less << | PHASE3 | RECRUITING | 2029-12-30 | Research Institute of Pediatri... More >>c Hematology, Oncology and Immunology, Moscow, 117997, Russian Federation Less << |
NCT03767660 | Blue Rubber Bleb Nevus Syndrom... More >>e|Venous Malformation Less << | PHASE4 | UNKNOWN | 2022-07-01 | Peking Union Medical College H... More >>ospital, Chinese Academy of Medicine Sciences, Beijing, Beijing, 100000, China Less << |
NCT02675153 | Crohn's Diseases | UNKNOWN | 2025-10-20 | Medical Center for Digestive D... More >>iseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, China Less << | |
NCT02042326 | Arteriovenous Malformations | PHASE2 | UNKNOWN | 2025-09-24 | UCL, Bruxelles, Belgium|CHU Am... More >>iens, Amiens, 80000, France|CHU Bordeaux, Bordeaux, 33000, France|CHU Dijon, Dijon, 21000, France|CHRU Lille, Lille, 59000, France|HCL Lyon, Lyon, 69000, France|APHM, Marseille, 13000, France|CHU Montpellier, Montpellier, 34000, France|CHU Nancy, Nancy, 54000, France|CHU Nice, Nice, 06000, France|APHP, Paris, 75000, France|CHU Strasbourg, Strasbourg, 67000, France|CHU Tours, Tours, 37000, France Less << |
NCT02123966 | Chronic Graft-versus-Host-Dise... More >>ase|Oral Mucosal Disease Due to Graft-versus-host Disease Less << | PHASE2 | TERMINATED | 2025-05-16 | Brigham and Women's Hospital, ... More >>Boston, Massachusetts, 02115, United States|Dana-Farber Cancer Institute, Boston, Massachusetts, 02115, United States Less << |
NCT00766649 | Age-Related Macular Degenerati... More >>on Less << | PHASE1|PHASE2 | COMPLETED | 2025-07-12 | National Institutes of Health ... More >>Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Less << |
NCT03364764 | Pure Red Cell Aplasia | PHASE4 | COMPLETED | 2021-05-01 | Peking Union Medical College H... More >>ospital, Beijing, Beijing, 100730, China Less << |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
1.09mL 0.22mL 0.11mL |
5.47mL 1.09mL 0.55mL |
10.94mL 2.19mL 1.09mL |