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  1. PI3K/Akt/mTOR
  2. PI3K
  3. CAL-130 Hydrochloride

CAL-130 Hydrochloride 是一種 PI3KδPI3Kγ 抑制劑,IC50 分別為 1.3 和 6.1 nM。

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CAL-130 Hydrochloride Chemical Structure

CAL-130 Hydrochloride Chemical Structure

CAS No. : 1431697-78-7

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10 mM * 1 mL in DMSO ¥2709
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Customer Review

Other Forms of CAL-130 Hydrochloride:

  • 生物活性

  • 實(shí)驗(yàn)參考方法

  • 純度 & 產(chǎn)品資料

  • 參考文獻(xiàn)

生物活性

CAL-130 is a PI3Kδ and PI3Kγ inhibitor with IC50s of 1.3 and 6.1 nM, respectively.

IC50 & Target[1]

p110δ

1.3 nM (IC50)

p110γ

6.1 nM (IC50)

p110β

56 nM (IC50)

p110α

115 nM (IC50)

體外研究
(In Vitro)

CAL-130 優(yōu)先抑制p110γ和p110δ催化域的功能。對(duì)于p110δ和p110γ,CAL-130的IC50值分別為1.3 nM和6.1 nM,而相比之下,對(duì)于p110α和p110β,其IC50值則為115 nM和56 nM。此外,CAL-130不會(huì)抑制對(duì)細(xì)胞一般功能和生存至關(guān)重要的其他細(xì)胞內(nèi)信號(hào)通路(例如,p38 MAPK或胰島素受體酪氨酸激酶)[1]。

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

體內(nèi)研究
(In Vivo)

通過(guò)向已患有T細(xì)胞急性淋巴細(xì)胞白血病(T-ALL)的Lck/Ptenfl/fl小鼠施用CAL-130,可以確定干擾PI3Kγ和PI3Kδ組合活性的臨床意義。用于生存研究的候選小鼠表現(xiàn)出病態(tài)外觀,白細(xì)胞計(jì)數(shù)(WBC)超過(guò)45,000每微升,外周血涂片中可見原始細(xì)胞,并且大部分循環(huán)細(xì)胞(超過(guò)75%)對(duì)Thy1.2和Ki-67雙染色呈陽(yáng)性反應(yīng)。這些小鼠每8小時(shí)接受一次口服劑量為10毫克/千克(mg/kg)的CAL-130治療,持續(xù)7天,并隨后被觀察直至接近瀕死狀態(tài)。盡管治療周期有限,CAL-130顯著延長(zhǎng)了治療組小鼠的中位生存期至45天,而對(duì)照組的中位生存期僅為7.5天[1]。

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

分子量

462.93

Formula

C23H23ClN8O

CAS 號(hào)
性狀

固體

顏色

Light yellow to yellow

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)
細(xì)胞實(shí)驗(yàn): 

DMSO 中的溶解度 : 50 mg/mL (108.01 mM; 超聲助溶; 吸濕的 DMSO 對(duì)產(chǎn)品的溶解度有顯著影響,請(qǐng)使用新開封的 DMSO)

H2O 中的溶解度 : < 0.1 mg/mL (insoluble)

配制儲(chǔ)備液
濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg
1 mM 2.1602 mL 10.8008 mL 21.6015 mL
5 mM 0.4320 mL 2.1602 mL 4.3203 mL
查看完整儲(chǔ)備液配制表

* 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)?個(gè)月內(nèi)使用,-20°C儲(chǔ)存時(shí),請(qǐng)?jiān)?個(gè)月內(nèi)使用。

  • 摩爾計(jì)算器

  • 稀釋計(jì)算器

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

質(zhì)量
=
濃度
×
體積
×
分子量 *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

濃度 (start)

C1

×
體積 (start)

V1

=
濃度 (final)

C2

×
體積 (final)

V2

動(dòng)物實(shí)驗(yàn):

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)娜芙夥桨浮?

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

  • 方案 一

    請(qǐng)依序添加每種溶劑: 10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 3 mg/mL (6.48 mM); 澄清溶液

    此方案可獲得 ≥ 3 mg/mL(飽和度未知)的澄清溶液。

    1 mL 工作液為例,取 100 μL 30.0 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 400 μL PEG300 中,混合均勻;再向上述體系中加入 50 μL Tween-80,混合均勻;然后再繼續(xù)加入 450 μL 生理鹽水 定容至 1 mL

    生理鹽水的配制:將 0.9 g 氯化鈉,溶解于 ddH?O 并定容至 100 mL,可以得到澄清透明的生理鹽水溶液。
  • 方案 二

    請(qǐng)依序添加每種溶劑: 10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 3 mg/mL (6.48 mM); 澄清溶液

    此方案可獲得 ≥ 3 mg/mL(飽和度未知)的澄清溶液。

    1 mL 工作液為例,取 100 μL 30.0 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 900 μL 20% 的 SBE-β-CD 生理鹽水水溶液 中,混合均勻。

    2 g SBE-β-CD(磺丁基醚 β-環(huán)糊精)粉末定容于 10 mL 的生理鹽水中,完全溶解至澄清透明。
動(dòng)物溶解方案計(jì)算器
請(qǐng)輸入動(dòng)物實(shí)驗(yàn)的基本信息:

給藥劑量

mg/kg

動(dòng)物的平均體重

g

每只動(dòng)物的給藥體積

μL

動(dòng)物數(shù)量

由于實(shí)驗(yàn)過(guò)程有損耗,建議您多配一只動(dòng)物的量
請(qǐng)輸入您的動(dòng)物體內(nèi)配方組成:
%
DMSO +
+
%
Tween-80 +
%
Saline
如果您的動(dòng)物是免疫缺陷鼠或者體弱鼠,建議 DMSO 中的在最后工作液體系中的占比盡量不超過(guò) 2%。
方案所需 助溶劑 包括:DMSO, ,均可在 MCE 網(wǎng)站選購(gòu)。 ,Tween 80,均可在 MCE 網(wǎng)站選購(gòu)。
計(jì)算結(jié)果
工作液所需濃度 : mg/mL
儲(chǔ)備液配制方法 : mg 藥物溶于 μL  DMSO(母液濃度為 mg/mL)。

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

您所需的儲(chǔ)備液濃度超過(guò)該產(chǎn)品的實(shí)測(cè)溶解度,以下方案僅供參考,如有需要,請(qǐng)與 MCE 中國(guó)技術(shù)支持聯(lián)系。
動(dòng)物實(shí)驗(yàn)體內(nèi)工作液的配制方法 : 取 μL DMSO 儲(chǔ)備液,加入 μL 。 μL ,混合均勻至澄清,再加 μL Tween 80,混合均勻至澄清,再加 μL 生理鹽水
連續(xù)給藥周期超過(guò)半月以上,請(qǐng)謹(jǐn)慎選擇該方案。
請(qǐng)確保第一步儲(chǔ)備液溶解至澄清狀態(tài),從左到右依次添加助溶劑。您可采用超聲加熱 (超聲清洗儀,建議頻次 20-40 kHz),渦旋吹打等方式輔助溶解。
純度 & 產(chǎn)品資料
參考文獻(xiàn)
Kinase Assay
[1]

IC50 values for CAL-130 inhibition of PI3K isoforms are determined in ex vivo PI3 kinase assays using recombinant PI3K. A ten-point kinase inhibitory profile is determined with ATP at a concentration consistent with the KM for each enzyme[1].

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

Cell Assay
[1]

Cell proliferation of CCRF-CEM cells or shRNA-transfected CCRF-CEM cells, in presence or absence of CAL-130 (1, 2.5 and 5 μM), is followed by cell counting of samples in triplicate using a hemocytometer and trypan blue. For apoptosis determinations of untransfected or shRNA-transfected CCRF-CEMs, cells are stained with APC-conjugated Annexin-V in Annexin Binding Buffer and analyzed by flow cytometry. For primary T-ALL samples, cell viability is assessed using the BD Cell Viability kit coupled with the use of fluorescentcounting beads. For this, cells are plated with MS5-DL1 stroma cells, and after 72 hr following CAL-130 treatment, cells are harvested and stained with an APC-conjugated antihuman CD45 followed by a staining with the aforementioned kit[1].

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

Animal Administration
[1]

Mice[1]
For subcutaneous xenograft experiments, luminescent CCRF-CEM (CEMluc) cells are generated by lentiviral infection with FUW-luc and selection with Neomycin. Luciferase expression is verified with the Dual-Luciferase Reporter Assay kit. 2.5×106 CEM-luc cells embedded in Matrigel are injected in the flank of NOD.Cg-Prkdcscid Il2rgtm1Wjl/Sz mice. After 1 week, mice are treated by oral gavage with vehicle (0.5% methyl cellulose, 0.1% Tween 80), or CAL-130 (10 mg/kg) every 8 hr daily for 4 days, and then tumors are imaged as follows: mice anesthetized by isoflurane inhalation are injected intraperitoneally with D-luciferin (50 mg/kg). Photonic emission is imaged with the in vivo imaging system. Tumor bioluminescence is quantified by integrating the photonic flux (photons per second) through a region encircling each tumor using the Living Image software package. Administration of D-luciferin and detection of tumor bioluminescence in Lck/Ptenfl/fl/Gt(ROSA)26Sortm1(Luc)Kael/J mice are performed in a similar manner.

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

參考文獻(xiàn)

完整儲(chǔ)備液配制表

* 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)?個(gè)月內(nèi)使用,-20°C儲(chǔ)存時(shí),請(qǐng)?jiān)?個(gè)月內(nèi)使用。

可選溶劑 濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.1602 mL 10.8008 mL 21.6015 mL 54.0038 mL
5 mM 0.4320 mL 2.1602 mL 4.3203 mL 10.8008 mL
10 mM 0.2160 mL 1.0801 mL 2.1602 mL 5.4004 mL
15 mM 0.1440 mL 0.7201 mL 1.4401 mL 3.6003 mL
20 mM 0.1080 mL 0.5400 mL 1.0801 mL 2.7002 mL
25 mM 0.0864 mL 0.4320 mL 0.8641 mL 2.1602 mL
30 mM 0.0720 mL 0.3600 mL 0.7201 mL 1.8001 mL
40 mM 0.0540 mL 0.2700 mL 0.5400 mL 1.3501 mL
50 mM 0.0432 mL 0.2160 mL 0.4320 mL 1.0801 mL
60 mM 0.0360 mL 0.1800 mL 0.3600 mL 0.9001 mL
80 mM 0.0270 mL 0.1350 mL 0.2700 mL 0.6750 mL
100 mM 0.0216 mL 0.1080 mL 0.2160 mL 0.5400 mL
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產(chǎn)品名稱:
CAL-130 Hydrochloride
目錄號(hào):
HY-16122B
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