| 產(chǎn)品描述： | LDN-214117 is an orally active ALK2 inhibitor with well-tolerated and good brain penetration. LDN-214117 has a high selectivity and low cytotoxicity for ALK2 with an IC50 value of 24 nM. LDN-214117 also is a specific bone morphogenetic proteins (BMPs) signaling inhibitor and has relatively selective inhibition for BMP6 with an IC50 value of 100 nM. LDN-214117 can be used for the research of fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine glioma (DIPG) |
| 靶點： |
IC50: 24 nM (ALK2); 27 nM (ALK1); 1,171 nM (ALK3); 3,000 nM (ALK5); 1,022 nM (BMP6); 27 nM (BMP2); 960 nM (BMP4); 16,000 nM (TGF-β1);ALK;TGF-beta/Smad |
| 體外研究： |
LDN-214117 has high inhibition and selectivity for ALK2 kinase proteins with an IC50 value of 24 nM. LDN-214117 has kinase activity for ALK1, ALK3 and ALK5 with IC50 values of 27 nM, 1,171 nM and 3,000 nM, respectively. LDN-214117 exhibits relatively selective inhibition for BMP6, BMP2 and BMP4 with IC50 values of 100 nM, 1,022 nM and 960 nM, respectively. LDN-214117 has inhibition of TGF-β1-induced transcriptional activity with an IC50 values of 16,000 nM. LDN-214117 (5 μM, 30 min, 3 h and 24 h) has time-dependent effect activity on gene regulation level and/ or a BMP signaling pathway other than SMAD-dependent that is responsible for ID1 targeting. LDN-214117 (5 μM, 24-120 h) reduces viability, proliferation and causes apoptosis of lung carcinoma cells LCLC-103H. LDN-214117 (5 μM, 0-48 h) suppresses wound healing and chemotactic potential of LCLC-103H cells. LDN-214117 (5 μM, 48 h) hinders growth of multicellular LCLC-103H spheroids. Cell Viability Assay Cell Line: LCLC-103H cells Concentration: 5 μM Incubation Time: 24 h, 48 h, 72 h and 96 h Result: Decreased markedly with time, counting approximately 60% of the vehicle control level at the 96-h measurement point. Western Blot Analysis Cell Line: LCLC-103H cells Concentration: 5 μM Incubation Time: 30 min, 3 h and 24 h Result: Diminished the increase of ID1 protein. Apoptosis Analysis Cell Line: LCLC-103H cells Concentration: 5 μM Incubation Time: 24 h, 48 h, 72 h and 96 h Result: Induced considerable death of LCLC-103H cell |
| 體內(nèi)研究： |
LDN-214117 (p.o., 25 mg/kg, daily, for 14 days) has well-tolerated in mice. Animal Model: NOD.SCID mice Dosage: 25 mg/kg Administration: p.o., daily, for 14 days Result: Showed good-tolerated in mice. |
| 參考文獻： |
1. Agustin H Mohedas, et al. Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J Med Chem. 2014 Oct 9;57(19):7900-15. 2. Jelena Mihajlovi?, et al. Inhibition of bone morphogenetic protein signaling reduces viability, growth and migratory potential of non-small cell lung carcinoma cells. J Cancer Res Clin Oncol. 2019 Nov;145(11):2675-2687. 3. Diana Carvalho, et al. ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma. Commun Biol. 2019 May 9;2:156. |
| 溶解性： |
soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.384 ml |
11.918 ml |
23.837 ml |
| 5 mM |
0.477 ml |
2.384 ml |
4.767 ml |
| 10 mM |
0.238 ml |
1.192 ml |
2.384 ml |
| 50 mM |
0.048 ml |
0.238 ml |
0.477 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
上海工商
危險品化學(xué)品經(jīng)營許可證（不帶存儲）
營業(yè)執(zhí)照(三證合一)
北京