Bomedemstat HCl

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Bomedemstat HCl

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

规格:

≥98%

包装与价格：

包装	价格(元)
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议

产品介绍

理化性质和储存条件

Molecular Formula: C28H35ClFN7O2;

Molecular Weight: 556.07

Synonym: IMG-7289 HCl; Bomedemstat HCl; IMG7289; IMG 7289; Bomedemstat hydrochloride;

Chemical Name: N-[(1S)-4-[[(1R,2S)-2-(4-Fluorophenyl)cyclopropyl]amino]-1-[(4-methyl-1-piperazinyl)carbonyl]butyl]-4-(1H-1,2,3-triazol-1-yl)benzamide dihydrochloride

InChi Key: PPKDUCDLYRHGFX-DVNXTAPYSA-N

InChi Code: InChI=1S/C28H34FN7O2.2ClH/c1-34-15-17-35(18-16-34)28(38)25(3-2-12-30-26-19-24(26)20-4-8-22(29)9-5-20)32-27(37)21-6-10-23(11-7-21)36-14-13-31-33-36;;/h4-11,13-14,24-26,30H,2-3,12,15-19H2,1H3,(H,32,37);2*1H/t24-,25-,26+;;/m0../s1

SMILES Code: O=C(N[C@H](C(N1CCN(C)CC1)=O)CCCN[C@H]2[C@H](C3=CC=C(F)C=C3)C2)C4=CC=C(N5N=NC=C5)C=C4.[H]Cl.[H]Cl

In Vitro	Bomedemstat (IMG-7289) selectively inhibits proliferation and induced apoptosis of JAK2V617F cells by concomitantly increasing expression and methylation of p53, and, independently, the pro-apoptotic factor PUMA and by decreasing the levels of its antiapoptotic antagonist BCL-XL[1]. Bomedemstat (25 nM, 50 nM) and Ruxolitinib (175 nM) synergize in inhibiting JAK2V617F-driven proliferation[1]. Bomedemstat (50 and 100 nM) exerts a pro-apoptotic effect on 3 key regulators of programmed cell death, TP53, BCL-XL, and PUMA[1]. Cell Viability Assay[1] Cell Line: The human cell lines SET-2 (ATCC 608) and HEK293 Concentration: 25 nM, 50 nM Incubation Time: 96 hours Result: 25 nM alone significantly reduced colony formation. Western Blot Analysis[1] Cell Line: SET-2 cells Concentration: 50 and 100 nM Incubation Time: Result: Decreased levels of the antiapoptotic protein BCL-XL and increased levels of the pro-apoptotic protein PUMA.
In Vivo	Once-daily treatment with Bomedemstat (IMG-7289; 45 mg/kg) normalizes or improves blood cell counts, reduces spleen volumes, restores normal splenic architecture, and reduces bone marrow fibrosis[1]. Animal Model: Mx1cre-Jak2V617F mice[1] Dosage: 45 mg/kg Administration: Administered daily by oral gavage for either 14, 42, or 56 consecutive days Result: In this Mx-Jak2V617F model of myeloproliferative neoplasm (MPN), mice developed severe splenomegaly (up to 10-fold increase in spleen weight). Splenic architecture was completely destroyed, eliminating demarcation of the white and red pulp. Treatment significantly reduced splenomegaly with a few treated mice normalizing their spleen weight. Remarkably, the 56-day course led to partial restoration of lymph follicles and spleen architecture by histological examination.

In Vitro

Bomedemstat (IMG-7289) selectively inhibits proliferation and induced apoptosis of JAK2V617F cells by concomitantly increasing expression and methylation of p53, and, independently, the pro-apoptotic factor PUMA and by decreasing the levels of its antiapoptotic antagonist BCL-XL[1]. Bomedemstat (25 nM, 50 nM) and Ruxolitinib (175 nM) synergize in inhibiting JAK2V617F-driven proliferation[1]. Bomedemstat (50 and 100 nM) exerts a pro-apoptotic effect on 3 key regulators of programmed cell death, TP53, BCL-XL, and PUMA[1]. Cell Viability Assay[1] Cell Line: The human cell lines SET-2 (ATCC 608) and HEK293 Concentration: 25 nM, 50 nM Incubation Time: 96 hours Result: 25 nM alone significantly reduced colony formation. Western Blot Analysis[1] Cell Line: SET-2 cells Concentration: 50 and 100 nM Incubation Time: Result: Decreased levels of the antiapoptotic protein BCL-XL and increased levels of the pro-apoptotic protein PUMA.

In Vivo

Once-daily treatment with Bomedemstat (IMG-7289; 45 mg/kg) normalizes or improves blood cell counts, reduces spleen volumes, restores normal splenic architecture, and reduces bone marrow fibrosis[1]. Animal Model: Mx1cre-Jak2V617F mice[1] Dosage: 45 mg/kg Administration: Administered daily by oral gavage for either 14, 42, or 56 consecutive days Result: In this Mx-Jak2V617F model of myeloproliferative neoplasm (MPN), mice developed severe splenomegaly (up to 10-fold increase in spleen weight). Splenic architecture was completely destroyed, eliminating demarcation of the white and red pulp. Treatment significantly reduced splenomegaly with a few treated mice normalizing their spleen weight. Remarkably, the 56-day course led to partial restoration of lymph follicles and spleen architecture by histological examination.