| CAS NO: | 1429882-07-4 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 2mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| Name: MRX-2843 CAS#: 1429882-07-4 Chemical Formula: C29H40N6O Exact Mass: 488.3264 Molecular Weight: 488.68 |
|
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Technical Information | Synonym: MRX-2843; UNC 2371; UNC2371A; MRX 2843; UNC-2371; UNC-2371A; MRX2843; UNC2371; UNC 2371A; Chemical Name: (1r,4r)-4-(2-((2-cyclopropylethyl)amino)-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexanol InChi Key: LBEJYFVJIPQSNX-SOAUALDESA-N InChi Code: InChI=1S/C29H40N6O/c1-33-14-16-34(17-15-33)19-22-4-6-23(7-5-22)27-20-35(24-8-10-25(36)11-9-24)28-26(27)18-31-29(32-28)30-13-12-21-2-3-21/h4-7,18,20-21,24-25,36H,2-3,8-17,19H2,1H3,(H,30,31,32)/t24-,25- SMILES Code: O[C@H]1CC[C@H](N2C=C(C3=CC=C(CN4CCN(C)CC4)C=C3)C5=CN=C(NCCC6CC6)N=C52)CC1 |
| Target | MERTK, FLT3[1] |
|---|---|
| In Vitro | In the Kasumi-1 cell line, treatment with MRX-2843 results in dose-dependent inhibition of MERTK phosphorylation. Decreased phosphorylation is evident at concentrations as low as 10 nM, with near-complete abrogation of MERTK activation at 100 to 300 nM. Similarly, treatment of Kasumi-1 cells with MRX-2843 mediates inhibition of downstream signaling through pathways important for tumor cell survival and proliferation. MRX-2843 treatment results in a decrease in relative cell numbers, with an IC50 of 143.5±14.1 nM, indicating that MRX-2843 significantly inhibits tumor cell proliferation and/or survival. Similarly, there are 34.1%±5.6% and 67.1%±2.7% apoptotic and dead cells in NOMO-1 cultures treated with 150 nM or 300 nM MRX-2843, respectively, compare with 6.8%±0.7% in vehicle-treated cultures (P<0.001). Treatment with 50 nM and 100 nM MRX-2843 results in 62.3%±6.4% and 84.1%±7.8% inhibition of colony formation, respectively, in Kasumi-1 cultures (P<0.01). Similarly, in NOMO-1 cultures, colony formation is inhibited by 54.8%±18.1% in response to treatment with 100 nM MRX-2843 (P<0.001). In MOLM-14 cells, treatment with MRX-2843 inhibits phosphorylation of FLT3 and downstream signaling through STAT5, ERK1/2, and AKT. Activation of FLT3 and its signaling pathways is almost completely abrogated by treatment with 50 nM MRX-2843, indicating somewhat higher cellular potency against FLT3 relative to MERTK[1]. |
| In Vivo | MRX-2843 is 78% orally bioavailable at a dose of 3 mg/kg with a Cmax of 1.3 μM and a t1/2 of 4.4 hours. In MOLM-14 parental xenografts, both quizartinib and MRX-2843 increase median survival compare with that of vehicle-treated mice (172.5 days versus 40 days and 121 days versus 36 days, respectively, P<0.001). In this model, quizartinib is more effective than MRX-2843 (P<0.005), although higher doses of MRX-2843 are not evaluated. In MOLM-14:D835Y xenografts, quizartinib prolongs survival compare with that of vehicle-treated mice, but the effect is minimal (median survival 45 days vs. 36 days, P<0.001). In MOLM-14:F691L xenografts, treatment with MRX-2843 prolongs survival by almost 2-fold in NSG and NSGS mice (median survival 87 vs. 44.5 days and 87 vs. 48 days, respectively, P<0.005). Increased survival is observed in response to treatment with MRX-2843 versus quizartinib, but the difference is only significant in NSG mice[1]. |
| References |
JCI Insight. 2016 Mar;1(3):e85630.
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