Navitoclax (Synonyms: ABT-263)
Navitoclax (ABT-263) 是有效，可口服的 Bcl-2 抑制劑，可與Bcl-xL，Bcl-2， Bcl-w等多種Bcl-2家族蛋白結(jié)合，Ki 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-xL, Bcl-2 and Bcl-w, with a Ki 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 | 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 | June 15, 2022 | Phase 1 | |
| NCT00878449 | AbbVie (prior sponsor, Abbott)|Genentech, Inc.|AbbVie | October 2009 | Phase 1 |
分子量：974.61
性狀：Solid
Formula：C47H55ClF3N5O6S3
CAS 號(hào)：923564-51-6
中文名稱(chēng)：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)
DMF : ≥ 100 mg/mL (102.61 mM)
DMSO : 75 mg/mL (76.95 mM; Need ultrasonic)
* "≥" means soluble, but saturation unknown.
| 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。
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
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