CAS號(hào)	923564-51-6	產(chǎn)地	國(guó)產(chǎn)
規(guī)格	5mg	級(jí)別	化工級(jí)
證書(shū)	ISO系列證書(shū)

Navitoclax (Synonyms: ABT-263)

Navitoclax (ABT-263) 是有效，可口服的 Bcl-2 抑制劑，可與Bcl-x_L，Bcl-2， Bcl-w等多種Bcl-2家族蛋白結(jié)合，K_i 值小于 1 nM。

生物活性

Navitoclax (ABT-263) is a potent and orally active Bcl-2 family protein inhibitor that binds to multiple anti-apoptotic Bcl-2 family proteins, such as Bcl-x_L, Bcl-2 and Bcl-w, with a K_i of less than 1 nM^[1].

體外研究(In Vitro)

Navitoclax (ABT-263) is active against approximately one-half of the cell lines of the PPTP in vitro panel. The median IC₅₀ for all of the lines in the panel is 1.91 µM^[1]. Navitoclax in combination with chemotherapy agents leads most ovarian cancer cell lines a synergistic response, and enhances the caspase activation in both SK-OV-3 and IGROV-1 cell lines^[2].

體內(nèi)研究(In Vivo)

Navitoclax (100 mg/kg; orally; 21-day treatment) enhances the activity of OSI-744 in vivo. As a single agent, 100 mg/kg Navitoclax alone dosed daily has no significant antitumor activity, whereas daily dosing of OSI-744 at 50 mg/kg results in significant tumor stasis (%TGI=52) during a 21-day treatment period. Notably, the combination of Navitoclax and OSI-744 dosed daily for 21 consecutive days results in 98% TGI and durable tumor regressions in 99% of treated tumor-bearing mice^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Mice with NCI-H1650 model^[3]
Dosage:	100 mg/kg
Administration:	Orally; daily; for 21 consecutive days
Result:	As a single agent, 100 mg/kg alone dosed daily had no significant antitumor activity. Notably, the combination with OSI-744 resulted in 98% TGI and durable tumor regressions in 99% of treated tumor-bearing mice.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT00406809	AbbVie (prior sponsor, Abbott)\|AbbVie	Chronic Lymphoid Leukemia\|Lymphoid Malignancies\|Non-Hodgkin′s Lymphoma\|Follicular Lymphoma\|Mantle Cell Lymphoma\|Peripheral T-cell Lymphoma	November 2006	Phase 1\|Phase 2
NCT05358639	Sunnybrook Health Sciences Centre\|Exactis Innovation\|Centre hospitalier de l′Université de Montréal (CHUM)\|Princess Margaret Hospital, Canada	High Grade Serous Carcinoma\|Triple Negative Breast Cancer\|Ovarian Cancer	June 15, 2022	Phase 1
NCT00878449	AbbVie (prior sponsor, Abbott)\|Genentech, Inc.\|AbbVie	Solid Tumors	October 2009	Phase 1

分子量：974.61

性狀：Solid

Formula：C₄₇H₅₅ClF₃N₅O₆S₃

CAS 號(hào)：923564-51-6

中文名稱：生根粉263

運(yùn)輸條件

Room temperature in continental US; may vary elsewhere.

儲(chǔ)存方式

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性數(shù)據(jù)

In Vitro:

DMF : ≥ 100 mg/mL (102.61 mM)

DMSO : 75 mg/mL (76.95 mM; Need ultrasonic)

* "≥" means soluble, but saturation unknown.

配制儲(chǔ)備液

濃度溶劑體積質(zhì)量	1 mg	5 mg	10 mg

1 mM	1.0261 mL	5.1303 mL	10.2605 mL
5 mM	0.2052 mL	1.0261 mL	2.0521 mL
10 mM	0.1026 mL	0.5130 mL	1.0261 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。-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。

In Vivo:

請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥方式選擇適當(dāng)?shù)娜芙夥桨?。以下溶解方案都?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： 60% phosal 50 propylene glycol (PG), 30% polyethylene glycol 400 (PEG400), 10% ethanol
Solubility: 12.5 mg/mL (12.83 mM); Suspended solution; Need ultrasonic
2.

請(qǐng)依序添加每種溶劑： 5% DMSO 40% PEG300 5% Tween-80 50% saline
Solubility: 5.5 mg/mL (5.64 mM); Suspended solution; Need ultrasonic
3.

請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: 2.08 mg/mL (2.13 mM); Suspended solution; Need ultrasonic
4.

請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: 2.08 mg/mL (2.13 mM); Suspended solution; Need ultrasonic
5.

請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (2.13 mM); Clear solution

參考文獻(xiàn)

[1]. Lock R1, et al. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1181-1189.  [Content Brief]
[2]. Wong M, et al. Navitoclax (ABT-263) reduces Bcl-x(L)-mediated chemoresistance in ovarian cancer models.Mol Cancer Ther. 2012 Apr;11(4):1026-1035.  [Content Brief]
[3]. Chen J, et al. The Bcl-2/Bcl-X(L)/Bcl-w inhibitor, navitoclax, enhances the activity of chemotherapeutic agents in vitro and in vivo. Mol Cancer Ther. 2011 Dec;10(12):2340-9.  [Content Brief]

注：產(chǎn)品僅用于科研