S63845 纯度:99.85% 1mg

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首页酶、辅酶及抑制剂MCE>

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S63845 纯度:99.85% 1mg

市场价：: 990.00

促销价：: ¥990.00

货号：HY-100741

品牌：MCE

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北京朝阳

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商品介绍
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S63845是有效的选择性骨髓细胞白血病1 (MCL1) 抑制剂，结合人MCL1的K_d 值为0.19 nM。

Description

S63845 is a potent and selective myeloid cell leukemia 1 (MCL1) inhibitor with a K_d of 0.19 nM for human MCL1.

IC₅₀ & Target

MCL1

0.19 nM (Kd)

In Vitro

The pro-survival protein myeloid cell leukemia 1 (MCL1) is over expressed in many cancers. S63845 is a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. The activity of S63845 is next evaluated in a panel of eight AML cell lines: all lines are sensitive to S63845 (IC₅₀=4-233 nM)^[1].

In Vivo

S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Intravenously injected (i.v.) S63845 exerts dose-dependent anti-tumour activity in human multiple myeloma (H929 and AMO1) xenografts in immunocompromised mice, with maximal tumour growth inhibition of 114% in the AMO1 model and 103% in the H929 model. At 25 mg/kg, S63845 induces complete regression in 7 out of 8 of the mice at 100 days after treatment in the AMO1 model^[1].

Solvent & Solubility

In Vitro:

DMSO : ≥ 100 mg/mL (120.59 mM)

H₂O : < 0.1 mg/mL (insoluble)

* "≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.2059 mL	6.0295 mL	12.0589 mL
5 mM	0.2412 mL	1.2059 mL	2.4118 mL
10 mM	0.1206 mL	0.6029 mL	1.2059 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in saline)

Solubility: 2.08 mg/mL (2.51 mM); Suspended solution; Need ultrasonic
2.

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% saline

Solubility: ≥ 2.08 mg/mL (2.51 mM); Clear solution

References

[1]. Kotschy A, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016 Oct 27;538(7626):477-482.

Kinase Assay ^[1]	10 mM HEPES pH 7.4, 175 mM NaCl, 25 μM EDTA, 1 mM TCEP, 0.01% P20 and 1% DMSO is used as a running buffer. The ligand surface is generated using double His-tagged proteins. Serial dilutions of the compound in buffer are injected over the protein surface. All sample measurements are performed at a flow rate of 30 μL per min (injection time 120 s, dissociation time 360 s). The sensor surface is regenerated by consecutive injections of 0.35 M EDTA pH 8.0 with 0.1 mg/mL trypsin, 0.5 M imidazole and 45% DMSO (60 s, 15 μL per min)^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[1]	Cells are treated with increasing doses of S63845 (typically 0.008, 0.025, 0.04, 0.2, 1, 5 μM) for 24 h. Cells are stained with Annexin V-FITC and propidium iodide, analysed on a FACS Calibur and live cells are recorded. Data are presented as per cent cell death induction relative to cells cultured in medium alone^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Mice: S63845 is formulated extemporaneously in 25 mM HCl, 20% 2-hydroxy propyl β -cyclo dextrin 20% and administrated at the 6.25, 12.5, 25 mg/kg for 0, 20, 40, 60, 80 days. Tumour growth inhibition (TGImax) is calculated^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Kotschy A, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016 Oct 27;538(7626):477-482.

Molecular Weight	829.26
Formula	C₃₉H₃₇ClF₄N₆O₆S
CAS No.	1799633-27-4
SMILES	CC(C(Cl)=C(OCCN1CCN(C)CC1)C=C2)=[C@@]2[C@]3=C(C4=CC=C(F)O4)SC5=NC=NC(O[C@H](CC6=C(OCC7=CC=NN7CC(F)(F)F)C=CC=C6)C(O)=O)=C53
Storage	4°C, stored under nitrogen
Shipping	Room temperature in continental US; may vary elsewhere