- |||||||||| Simulect (basiliximab) / Novartis
PK/PD data, Journal: Pharmacokinetics of immunosuppressive agents during hemoperfusion in a sheep model. (Pubmed Central) - Nov 6, 2023 The maximum absolute adsorbed amounts (95% CI) for TAC, CYA, MMF, EVER, and MP were 0.040 (0.028-0.053), 1.15 (0.39-1.91), 4.17 (2.00-6.35), 0.0163 (0.007-0.026), and 53.4?mg (20.9-85.9), respectively, indicating an adsorption of less than 5% of the daily administered dosages for all investigated substances. In this large animal model, CytoSorb
- |||||||||| fludarabine IV / Generic mfg., cyclophosphamide / Generic mfg., cyclosporin A microemulsion / Generic mfg.
Trial completion date, Trial primary completion date: Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases (clinicaltrials.gov) - Nov 3, 2023 P=N/A, N=200, Recruiting, These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents. Trial completion date: Oct 2023 --> Oct 2025 | Trial primary completion date: Oct 2023 --> Oct 2024
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Sitagliptin for Prevention of aGVHD in Patients Received Alternative Donor Transplantations: A Prospective, Multicenter, Open-Label, Randomized Controlled Trial (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6383; P3 190 eligible p ts (18-60 years) were planned randomly assigned in a 1:1 ratio to either a sitagliptin group (600mg sitagliptin taken orally every 12 hours on day -1 to +14, plus conventional prophylaxis including Cyclosporin A(CsA)/ tacrolimus (FK506) , MTX, MMF and ATG ) and a conventional prophylaxis control group ( CsA/FK506 , MTX, MMF and ATG )...Furthermore, sitagliptin is ready availab le , eas y of administration, safe, and relatively inexpensive . It remains to be followed up whether it would increase infection and relapse or improve the prognosis of patients after allo-HSCT.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Actemra IV (tocilizumab) / Roche, JW Pharma
Optimized Double-Unit Cord Blood Transplantation Mitigates Transplant-Related Mortality Resulting in High Progression-Free Survival in Adults with Hematologic Malignancies (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6376; Letermovir is highly effective completely preventing CMV infections & may contribute to the reduced aGVHD-related mortality recently (as compared to the pre-tocilizumab era), since avoidance of CMV antiviral therapy toxicities greatly facilitates aGVHD prevention & therapy. Given the rapid availability of cryopreserved unmanipulated CB grafts & frequent limitations of URD availability for minority populations, optimized dCBT is a highly attractive curative therapy for acute leukemias & other high-risk myeloid malignancies warranting prospective multi-center investigation.
- |||||||||| cyclosporin A microemulsion / Generic mfg.
PPIL2 Is a Target of the JAK2-STAT5 Pathway and Mediates p53 Polyubiquitination and Degradation (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_5959; Our findings reveal PPIL2 as an effector of the JAK2/STAT5 pathway and Plek2 signalosome. PPIL2 plays an important role in normal erythropoiesis and the pathogenesis of JAK2 V617F -induced MPNs by degrading p53, pointing to PPIL2 as a potential therapeutic target for the treatment of MPNs.
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma
High Progression-Free Survival with Low Relapse Rates after Double-Unit Cord Blood Transplantation in Patients with High-Risk AML (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2648; This observation, together with the mitigation of TRM in recent years due to the optimized transplant practices in adult dCBT (see Politikos et al , ASH 2023), makes intermediate intensity dCBT an attractive strategy for AML patients with a suitable dCB graft & high-risk disease. Our findings warrant prospective multi-center investigation with correlative studies to elucidate the biology of CB-derived GVL.
- |||||||||| cyclosporin A microemulsion / Generic mfg.
Crosstalk between NFAT and NF?B Signaling Regulates NK Cell Immunosurveillance (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1576; Available data indicate that NFAT activity is dispensable for development of NK cells, whereas effects of the immunosuppressive drugs cyclosporin A and tacrolimus, that inhibit calcineurin and consecutively NFAT, implicate an involvement of the NFAT family in NK cell function...Taken together, our results identify NFAT as a negative regulator of NK cell function. In addition, we provide the first evidence for a direct functional involvement of NFAT1 and NFAT2 in NK cell antitumor reactivity by regulation tumor infiltration and cytotoxicity of NK cell.
- |||||||||| cyclosporin A microemulsion / Generic mfg.
Journal: Advances of the novel immunosuppressant brasilicardin A (Pubmed Central) - Nov 1, 2023 BraA is more potent in a mouse mixed lymphocyte reaction and less toxic against various human cell lines compared with the known clinical immunosuppressants, such as cyclosporin A, ascomycin and tacrolimus...However, the development of this promising immunosuppressant as drug for medical use is so far hindered because BraA has the unusual and synthetically challenging skeleton and shows the low-yield production in the natural pathogenic producer. This review introduces the molecular structure of BraA, its activity, mechanism of action, chemical synthesis of BraA analogs, heterologous expression of gene cluster, and an application of combining microbial and chemical synthesis for production of BraA, with the aim to facilitate the efficient production of BraA and its analogs.
- |||||||||| Lupkynis (voclosporin) / Aurinia Pharma, Otsuka
Review, Journal: Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis. (Pubmed Central) - Oct 31, 2023 However, the traditional CNI, cyclosporine A and tacrolimus, have a narrow therapeutic range, need monitoring of drug levels, and their use is associated with nephrotoxicity and metabolic alterations...Here, we review the unique chemistry, pharmacology, and toxicity profile of VOC, summarize the efficacy and safety data from the AURA-LV and AURORA-1 trials, and discuss the following four possible options to implement VOC into the management of lupus nephritis, namely regarding B cell-targeting therapy with belimumab (BEL)...VOC-BEL sequential therapy, or 4. alternative options for the rapid antiproteinuric effect of VOC.
- |||||||||| chlorpromazine / Generic mfg., cyclosporin A microemulsion / Generic mfg.
Journal: Side-Chain Immune Oxysterols Induce Neuroinflammation by Activating Microglia. (Pubmed Central) - Oct 28, 2023 through a mechanism amenable to pharmacologic intervention. The activation of microglia and subsequent neuroinflammation elicited by the immune oxysterols can contribute to the development of neurodegenerative diseases.
- |||||||||| cyclosporin A microemulsion / Generic mfg.
Journal: The novel cyclophilin inhibitor C105SR reduces hepatic ischaemia-reperfusion injury via mitoprotection. (Pubmed Central) - Oct 20, 2023 Their SR diastereoisomers carried the activity of the racemic mixture and exhibited mitoprotective properties superior to those of the known macrocyclic cyclophilin inhibitors cyclosporin A and alisporivir...However, no effective therapies are available to prevent or treat this devastating syndrome. An attractive strategy to prevent hepatic IRI aims at reducing cell death by targeting mitochondrial permeability transition pore opening, a phenomenon regulated by cyclophilin D. Here, we identified a new small-molecule cyclophilin inhibitor, and demonstrated the enhanced mitoprotective and hepatoprotective properties of one of its diastereoisomers both in
- |||||||||| cyclosporin A microemulsion / Generic mfg.
Preclinical, Journal: Arsenic Exposure-Induced Acute Kidney Injury by Regulating SIRT1/PINK1/Mitophagy Axis in Mice and in HK-2 Cells. (Pubmed Central) - Oct 16, 2023 Interestingly, the inhibition of mitophagy by cyclosporin A (CsA) further exacerbated NaAsO-induced nephrotoxicity and inflammation in HK-2 cells...In addition, we confirmed that PINK1-/Parkin-dependent mitophagy played a protective role against NaAsO-induced acute kidney injury. Therefore, activation of SIRT1 and mitophagy may represent a novel therapeutic target for the prevention and treatment of NaAsO-induced acute renal injury.
- |||||||||| cyclosporin A microemulsion / Generic mfg.
Novel Cyclosporine analogues enhance transduction efficiency in human stem cells via IFITM3 degradation () - Oct 15, 2023 - Abstract #ESGCT2023ESGCT_531; In this study we have used structure?aided design to chemically modify Cyclosporine A to eliminate unwanted Cyclophillin A targeting and enhance IFITM3 targeting...CycloVect is not immunosuppressive because it does not target CypA. It represents a promising new agent to enhance and standardise HSPC modification outcomes as well as a valuable tool to probe IFITM3 biology and restriction mechanisms.
- |||||||||| sirolimus / Generic mfg.
Journal, Gene Signature, Gene therapy: Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques. (Pubmed Central) - Oct 14, 2023 In study 1, no immunosuppression was compared with prednisolone, rapamycin (or sirolimus), rapamycin and cyclosporin A in combination, and cyclosporin A and azathioprine in combination...Study 2 compared no immunosuppression with prednisolone alone or in combination with rapamycin or methotrexate...Additionally, a significant reduction in the plasma cell gene signature was observed with prednisolone/rapamycin, suggesting that rapamycin's tolerogenic effects may include plasma cell differentiation blockade. Immunosuppression with prednisolone and rapamycin in combination could improve therapeutic outcomes in AAV vector gene therapy.
- |||||||||| liposomal cyclosporine A (LiCsA) / Zambon
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date: Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-2) (clinicaltrials.gov) - Oct 10, 2023 P3, N=220, Active, not recruiting, Recruiting --> Active, not recruiting | N=110 --> 220 | Trial completion date: Jun 2024 --> Nov 2024 Recruiting --> Active, not recruiting | N=152 --> 220 | Trial completion date: Sep 2023 --> Oct 2024 | Trial primary completion date: Aug 2023 --> Apr 2024
- |||||||||| cyclosporin A microemulsion / Generic mfg.
Journal: Role of ABC Proteins in Secondary Metabolism and Immune (=Defensive) Response in Seaweeds. (Pubmed Central) - Oct 2, 2023 Assays with Rhodamine-123 and cyclosporine A (CSA) revealed the presence of ABC transporters in CC membrane of Laurencia dendroidea...The latter subfamily is known to be associated with the transport of plant terpenes. Our results shed new light on the role of ABC proteins in key mechanisms of the defensive system in seaweeds against fouling and herbivory.
- |||||||||| cyclosporin A microemulsion / Generic mfg.
Preclinical, Journal: Rectal administration of tacrolimus protects against post-ERCP pancreatitis in mice. (Pubmed Central) - Oct 1, 2023 Our results shed new light on the role of ABC proteins in key mechanisms of the defensive system in seaweeds against fouling and herbivory. Our results underscore the effectiveness and clinical utility of rectal Tac for PEP prophylaxis.
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