GW3965 hydrochloride
GW3965 hydrochloride 是肝 X 受體 (LXR) 激動(dòng)劑，對(duì) hLXRα 和 hLXRβ 的 EC50 分別為 190 nM 和 30 nM。
生物活性
GW3965 hydrochloride is a potent and selective liver X receptor (LXR) agonist with EC50s of 190 nM and 30 nM for hLXRα and hLXRβ, respectively[1][2][3].
IC50 & Target
EC50: 190 nM (hLXRα), 30 nM (hLXRβ)[4]
體外研究(In Vitro)
GW3965 hydrochloride promotes GBM cell death in vitro with enhanced efficacy in EGFRvIII-expressing tumor cells. GW3965 hydrochloride up-regulates expression of the cholesterol transporter gene ABCA1 and the E3 ubiquitin ligase IDOL and reduces LDLR levels[2]. LXR ligands inhibits platelet aggregation and calcium mobilization stimulated by collagen or CRP. GW3965 hydrochloride (1 or 5 μM) displays a minor inhibitory effect on fibrinogen binding and P-selectin exposure, when platelets are stimulated with 1 μg/mL CRP. But using higher concentrations of GW3965 hydrochloride (10 μM) or T0901317 (40 μM), the levels of fibrinogen and P-selectin on the platelet surface are reduced[3].
體內(nèi)研究(In Vivo)
GW3965 hydrochloride induces an increase of neuroactive steroids in the spinal cord, the cerebellum and the cerebral cortex of STZ-rats, but not in the CNS of non-pathological animals. GW3965 hydrochloride treatment induces an increase of dihydroprogesterone in the spinal cord of diabetic animals in association with an increase of myelin basic protein expression[1]. GW3965 hydrochloride (40 mg/kg, p.o.) strongly induces ABCA1 expression and reduces LDLR expression, and this is accompanied by 59% inhibition of tumor growth, and a 25-fold increase in GBM cell apoptosis in vivo[2]. GW3965 hydrochloride (2 mg/kg, i.v.) increases bleeding time and modulated platelet thrombus formation in vivo[3].
分子量：618.51
性狀：Solid
Formula：C33H32Cl2F3NO3
CAS 號(hào)：405911-17-3
運(yùn)輸條件：Room temperature in continental US; may vary elsewhere.
儲(chǔ)存方式
4°C, sealed storage, away from moisture
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
溶解性數(shù)據(jù)
DMSO : 100 mg/mL (161.68 mM; Need ultrasonic)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
| 濃度溶劑體積質(zhì)量 | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.6168 mL | 8.0839 mL | 16.1679 mL |
| 5 mM | 0.3234 mL | 1.6168 mL | 3.2336 mL |
| 10 mM | 0.1617 mL | 0.8084 mL | 1.6168 mL |
請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲(chǔ)備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)月內(nèi)使用，-20°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)月內(nèi)使用。
以下溶解方案都請(qǐng)先按照 In Vitro 方式配制澄清的儲(chǔ)備液，再依次添加助溶劑：
——為保證實(shí)驗(yàn)結(jié)果的可靠性，澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用； 以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的方式助溶
- 1.
請(qǐng)依序添加每種溶劑： corn oil
Solubility: 10 mg/mL (16.17 mM); Suspended solution; Need ultrasonic
- 2.
請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (4.04 mM); Clear solution
- 3.
請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: 2.5 mg/mL (4.04 mM); Suspended solution; Need ultrasonic
- 4.
請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.04 mM); Clear solution
參考文獻(xiàn)
[1]. Mitro, Nico., et al. LXR and TSPO as new therapeutic targets to increase the levels of neuroactive steroids in the central nervous system of diabetic animals. Neurochemistry International (2012), 60(6), 616-621. [Content Brief]
[2]. Guo, Deliang., et al. An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR-Dependent Pathway. Cancer Discovery (2011), 1(5), 442-456.
[3]. Spyridon, Michael., et al. LXR as a novel antithrombotic target. Blood (2011), 117(21), 5751-5761. [Content Brief]
[4]. Collins JL, et al. Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J Med Chem. 2002 May 9;45(10):1963-6. [Content Brief]
注：產(chǎn)品僅用于科研
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