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Apilimod

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Chemical Structure| 541550-19-0 同义名 : 阿吡莫德 ;STA 5326;LAM-002A free base;AIT-101
CAS号 : 541550-19-0
货号 : A149227
分子式 : C23H26N6O2
纯度 : 99%+
分子量 : 418.491
MDL号 : MFCD09954108
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(250.9 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase that synthesizes two phosphoinositides (PIs), regulating degradative and recycling endosomal trafficking, cytoskeletal rearrangement and autophagy. Apilimod is a 1,3,5-triazine derivative that binds to and inhibits PIKfyve kinase activity with an IC50 value of 14 nM. Treatment of apilimod (10 nM and 1 μM) for 120min decreased PI(3,5)P2 in HeLa cells at a dose-dependent manner. RAW264.7 cells treated with 10 nM Apilimod for 3h showed enlarged vacuoles due to the disruption of PIKfyve activity. In A549 cells, overexpression of wild-type PIKfyve resulted in the disappearance of vacuoles induced by 10 nM apilimod. Bone-marrow-derived dendritic cells from mutant mice demonstrated extensive vacuole formation with the treatment of 1 μM apilimod[3]. Apilimod showed selective antiproliferative activity in B-NHL cells with an IC50 value of 142 nM. After the treatment of 200 nM apilimod for 3 days, increased apoptosis was shown in SU-DHL-10 B-NHL cells. In a subcutaneous daudi burkitt lymphoma xenograft model, apilimod (50 - 150 mg/kg free base; p.o., once a day) displayed tumor growth inhibition at a dose-dependent manner. The growth inhibition was also observed in SU-DHL-6 DLBCL model treated with both apilimod (41 mg/kg free base, p.o., twice a day) and rituximab (7 mg/kg, i.p.)[4].
作用机制 Apilimod is a potent, highly selective PIKfyve inhibitor that binds to the PIKfyve domain (amino acids 1522 to 2098) to block the phosphotransferase activity of PIKfyve, thereby inhibiting IL-12/23p40[3].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02594384 Lymphoma, Non-Hodgkin; Leukema... 展开 >>i, Chronic Lymphocytic 收起 << Phase 1 Recruiting December 2019 United States, Alabama ... 展开 >> Clearview Cancer Institute Recruiting Huntsville, Alabama, United States, 35805 Contact: Avitra Bone, RN    256-705-4283    studycoordinator@ccihsv.com    Principal Investigator: Marshall Schreeder, MD          United States, Florida Mayo Clinic Recruiting Jacksonville, Florida, United States, 32224 Contact: Lisa Melfi    904-953-3320    melfi.lisa@mayo.edu    Principal Investigator: Taimur Sher, MD          United States, Georgia Winship Cancer Institute at Emory University Recruiting Atlanta, Georgia, United States, 30322 Contact: Kaylan Dixon    404-778-4449    kaylan.dixon@emory.edu    Principal Investigator: Jonathan Cohen, MD          United States, Indiana Horizon Oncology Research, Inc. Recruiting Lafayette, Indiana, United States, 47905 Contact: Wael A Harb, MD    765-446-5111    wharb@horizonbioadvance.com    Principal Investigator: Wael A Harb, MD          United States, Massachusetts Massachusetts General Hospital Recruiting Boston, Massachusetts, United States, 02114 Contact: Lauren Ramos    617-643-9607    lramos7@mgh.harvard.edu    Principal Investigator: Jeremy Abramson, MD          United States, Minnesota Mayo Clinic Recruiting Rochester, Minnesota, United States, 55905 Contact: Corinne Parker    507-266-3784    parker.corinne@mayo.edu    Principal Investigator: Stephen Ansell, MD          United States, New York New York University School of Medicine Recruiting New York, New York, United States, 10016 Contact: Ion Marinescu    646-501-7920    Ion.Marinescu@nyumc.org    Principal Investigator: Catherine Diefenbach, MD          Weill Cornell Medical College Recruiting New York, New York, United States, 10021 Contact: Rita Gazivoda    212-746-0702    rig9021@med.cornell.edu    Principal Investigator: Sarah Rutherford, MD          United States, Texas University of Texas MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Linda Claret    713-792-1044    lcclaret@mdanderson.org    Principal Investigator: Loretta Nastoupil, MD          United States, Virginia Virginia Cancer Specialists Recruiting Fairfax, Virginia, United States, 22031 Contact: VCS Phase 1 Team    703-208-3192    Karin.Choquette@usoncology.com    Principal Investigator: Dipti Patel-Donnelly, MD          United States, Washington Virginia Mason Medical Center Recruiting Seattle, Washington, United States, 98101 Contact: Anas Najjar    206-287-5671    Anas.Najjar@virginiamason.org    Principal Investigator: David Aboulafia, MD 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.39mL

0.48mL

0.24mL

11.95mL

2.39mL

1.19mL

23.90mL

4.78mL

2.39mL
参考文献

[1]Gayle S, Landrette S, et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017 Mar 30;129(13):1768-1778.

[2]Wada Y, Lu R, et al. Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor. Blood. 2007;109(3):1156-64

[3]Cai X, Xu Y, Cheung AK, Tomlinson RC, Alcázar-Román A, Murphy L, Billich A, Zhang B, Feng Y, Klumpp M, Rondeau JM, Fazal AN, Wilson CJ, Myer V, Joberty G, Bouwmeester T, Labow MA, Finan PM, Porter JA, Ploegh HL, Baird D, De Camilli P, Tallarico JA, Huang Q. PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-like receptor signaling. Chem Biol. 2013 Jul 25;20(7):912-21.

[4]Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, Ferguson SM, Mandelkern T, Zheng M, Xu T, Rothberg J, Lichenstein H. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017 Mar 30;129(13):1768-1778.