Momelotinib sulfate(Synonyms: CYT387 sulfate salt)

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

Momelotinib sulfate (Synonyms: CYT387 sulfate salt) 纯度: 98.04%

Momelotinib sulfate (CYT387 sulfate salt) 是一种 ATP竞争性的 JAK1/JAK2 抑制剂,IC50 分别为 11 nM/18 nM,作用于JAK3时,IC50 为 155 nM。

Momelotinib sulfate(Synonyms: CYT387 sulfate salt)

Momelotinib sulfate Chemical Structure

CAS No. : 1056636-06-6

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ¥1142 In-stock
5 mg ¥850 In-stock
10 mg ¥1252 In-stock
50 mg ¥3464 In-stock
100 mg ¥5388 In-stock
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

Momelotinib sulfate 相关产品

相关化合物库:

  • Drug Repurposing Compound Library Plus
  • Clinical Compound Library Plus
  • Bioactive Compound Library Plus
  • Apoptosis Compound Library
  • Epigenetics Compound Library
  • Immunology/Inflammation Compound Library
  • JAK/STAT Compound Library
  • Kinase Inhibitor Library
  • Stem Cell Signaling Compound Library
  • Anti-Cancer Compound Library
  • Clinical Compound Library
  • Autophagy Compound Library
  • Anti-Aging Compound Library
  • Drug Repurposing Compound Library
  • Differentiation Inducing Compound Library
  • Reprogramming Compound Library
  • Anti-COVID-19 Compound Library
  • Anti-Breast Cancer Compound Library
  • Anti-Lung Cancer Compound Library
  • Anti-Pancreatic Cancer Compound Library
  • Anti-Blood Cancer Compound Library
  • Anti-Liver Cancer Compound Library
  • Rare Diseases Drug Library

生物活性

Momelotinib sulfate (CYT387 sulfate salt) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, 10-fold selectivity versus JAK3 (IC50=155 nM).

IC50 & Target[1]

JAK1

11 nM (IC50)

JAK2

18 nM (IC50)

JAK3

155 nM (IC50)

体外研究
(In Vitro)

Momelotinib sulfate (CYT387 sulfate salt) inhibits growth of Ba/F3-JAK2V617F and human erythroleukemia (HEL) cells (IC50=1.5 μM) or Ba/F3-MPLW515L cells (IC50=200 nM), but has considerably less activity against BCR-ABL harboring K562 cells (IC50=58 μM) and FLT3 mutation harboring MV4-11 cells (IC50=3 μM). Proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated with IL-3 is inhibited with an IC50 value of 1.4 μM, consistent with the established role of IL-3-dependent signaling in the parental cell line[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

Momelotinib sulfate (CYT387 sulfate salt) at twice the dose used in disease model (50 and 100 mg/kg) has little to no effect on peripheral blood counts over a period of 8 weeks. Median plasma peak concentrations are 7.1 μM with the lower dose and 32.1μM with the higher dose, with a half-life of approximately 2 hours. Trough levels at 12 hours are 10nM for the 25 mg/kg and 900nM for the 50 mg/kg dose. At day 34 after transplantation, the mean white blood cell counts and hematocrit values of the entire cohort exceeded the normal range for Balb/c mice by more than 1 SD. At this point, 6 mice are sacrificed and subjected to autopsy. In the remaining animals, treatment is initiated with 25 mg/kg Momelotinib sulfate (CYT387 sulfate salt), 50 mg/kg Momelotinib sulfate (CYT387 sulfate salt), or vehicle, administered twice daily by oral gavage (12 mice per treatment group). A rapid drop of the white cell counts is apparent in both dose cohorts as early as 6 days after initiation of treatment and a decline of the hematocrit is apparent after 20 days[2]. After oral dosing, Momelotinib sulfate (CYT387 sulfate salt) exhibits high plasma concentrations (Cmax= 40.4 μM; Tmax=4 h), with quantitative absolute oral bioavailability and an apparent half life of 2.4 h. The high oral bioavailability, can likely be partly ascribed to the low blood clearance of Momelotinib sulfate (CYT387 sulfate salt) (6.3 mL/min/kg) and therefore low susceptibility to hepatic first pass metabolism[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

610.62

Formula

C23H26N6O10S2

CAS 号

1056636-06-6

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

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

溶解性数据
In Vitro: 

DMSO : 220 mg/mL (360.29 mM; Need ultrasonic)

H2O : 100 mg/mL (163.77 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.6377 mL 8.1884 mL 16.3768 mL
5 mM 0.3275 mL 1.6377 mL 3.2754 mL
10 mM 0.1638 mL 0.8188 mL 1.6377 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 5.5 mg/mL (9.01 mM); Clear solution

    此方案可获得 ≥ 5.5 mg/mL (9.01 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 55.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 5.5 mg/mL (9.01 mM); Clear solution

    此方案可获得 ≥ 5.5 mg/mL (9.01 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 55.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 5.5 mg/mL (9.01 mM); Clear solution

    此方案可获得 ≥ 5.5 mg/mL (9.01 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 55.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.

    [2]. Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25), 5232-5240.

    [3]. Burns CJ, et al. Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs). Bioorg Med Chem Lett. 2009 Oct 15;19(20):5887-92.

Kinase Assay
[1]

Glutathione-S-transferase (GST)-tagged JAK kinase domains expressed in insect cells are purified before use in a peptide substrate phosphorylation assay. Assays are carried out in 384-well optiplates using an Alphascreen Protein Tyrosine Kinase P100 detection kit and a PerkinElmer Fusion Alpha instrument[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

Ba/F3 cells expressing JAK2V617F (Ba/F3-JAK2V617F) and MPLW515L (Ba/F3-MPLW515L) mutants, as well as CHRF-288-11 (JAK2T875N) and CMK (JAK3A572V) cells are used. The TEL/JAK2 and TEL/JAK3 fusions are generated and introduced into Ba/F3 murine cells. TheTEL/JAK2– or TEL/JAK3-transfected cells are cultured in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% fetal calf serum (FCS). Ba/F3 wild-type cells are cultured in RPMI containing 10% FCS supplemented with 5 ng/mL murine IL-3. Proliferation is measured using the Alamar Blue assay after incubating for 72 h at 37°C with 5% CO2[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Mice[2]

On day 32 after bone marrow transplantation (when all mice exhibit severe leukocytosis and erythrocytosis), mice are assigned to 3 groups such that each group has equivalent average body weight and blood counts. Momelotinib (CYT387) is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone, Chromasolv Plus). Subsequently, the Momelotinib/NMP mix is diluted with 0.14M Captisol to a concentration of 6 mg/mL and further diluted with 0.1M Captisol to a final concentration of 4 mg/mL. All 3 groups of mice (n=12 per group) are administered Momelotinib (CYT387) by oral gavage twice daily at 10- to 12-hour intervals from day 34 after bone marrow transplantation to day 82 (end of experiment). Mice receive NMP/Captisol without Momelotinib (CYT387) (0 mg/kg group), 25 mg/kg Momelotinib, or 50 mg/kg Momelotinib. At day 82 after bone marrow transplantation, all mice are euthanized for analysis except for 2 mice each from the 50 mg/kg and 25 mg/kg groups, which are taken off Momelotinib (CYT387) treatment and followed for 45 additional days. For assessment of the effects of Momelotinib (CYT387) on normal blood counts, naive Balb/c mice are administered vehicle control, 50 mg/kg, or 100 mg/kg Momelotinib (CYT387) in an identical fashion as described for the bone marrow transplant experimental mouse cohort. Peripheral blood is drawn at day 14, 28, 42, and 56 and levels of red cells, white cells, reticulocytes, granulocytes, lymphocytes, and monocytes are analyzed.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.

    [2]. Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25), 5232-5240.

    [3]. Burns CJ, et al. Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs). Bioorg Med Chem Lett. 2009 Oct 15;19(20):5887-92.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务

Momelotinib Mesylate(Synonyms: CYT387 Mesylate)

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

Momelotinib Mesylate (Synonyms: CYT387 Mesylate)

Momelotinib Mesylate (CYT387 Mesylate) 是一种 ATP 竞争性的 JAK1/JAK2 抑制剂,IC50 值分别为 11 nM/18 nM,对其选择性约是 JAK3 的 10 倍。

Momelotinib Mesylate(Synonyms: CYT387 Mesylate)

Momelotinib Mesylate Chemical Structure

CAS No. : 1056636-07-7

规格 是否有货
100 mg   询价  
250 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

Momelotinib Mesylate 的其他形式现货产品:

Momelotinib Momelotinib sulfate

生物活性

Momelotinib Mesylate (CYT387 Mesylate) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, appr 10-fold selectivity versus JAK3.

IC50 & Target[1]

JAK1

11 nM (IC50)

JAK2

18 nM (IC50)

JAK3

155 nM (IC50)

体外研究
(In Vitro)

Momelotinib Mesylate is an inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, appr 10-fold selectivity versus JAK3. Momelotinib inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, Momelotinib also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, Momelotinib has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2 μM-4 μM[1]. Momelotinib inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, Momelotinib induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

In a murine MPN model, Momelotinib normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

510.57

Formula

C24H26N6O5S

CAS 号

1056636-07-7

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.

参考文献
  • [1]. Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.

    [2]. Monaghan KA, et al. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia, 2011, 25(12), 1891-1899.

    [3]. Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25), 5232-5240.

Cell Assay
[1]

Ba/F3 cells expressing JAK2V617F (Ba/F3-JAK2V617F) and MPLW515L (Ba/F3-MPLW515L) mutants, as well as CHRF-288-11 (JAK2T875N) and CMK (JAK3A572V) cells are used. The TEL/JAK2 and TEL/JAK3 fusions are generated and introduced into Ba/F3 murine cells. The TEL/JAK2- or TEL/JAK3-transfected cells are cultured in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% fetal calf serum (FCS). Ba/F3 wild-type cells are cultured in RPMI containing 10% FCS supplemented with 5 ng/mL murine IL-3. Proliferation is measured using the Alamar Blue assay after incubating for 72 hours at 37°C with 5% CO2[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[3]

Mice[3]
On day 32 after bone marrow transplantation (when all mice exhibit severe leukocytosis and erythrocytosis), mice are assigned to 3 groups such that each group had equivalent average body weight and blood counts. Momelotinib is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone). Subsequently, the Momelotinib/NMP mix is diluted with 0.14 M Captisol to a concentration of 6 mg/mL and further diluted with 0.1 M Captisol to a final concentration of 4 mg/mL. All 3 groups of mice (n=12 per group) are administered Momelotinib by oral gavage twice daily at 10- to 12-hour intervals from day 34 after bone marrow transplantation to day 82 (end of experiment). Mice receive NMP/Captisol without Momelotinib (0 mg/kg group), 25 mg/kg Momelotinib, or 50 mg/kg Momelotinib. At day 82 after bone marrow transplantation, all mice are euthanized for analysis except for 2 mice each from the 50 mg/kg and 25 mg/kg groups, which are taken off Momelotinib treatment and followed for 45 additional days. For assessment of the effects of Momelotinib on normal blood counts, naive Balb/c mice are administered vehicle control, or 50 mg/kg, or 100 mg/kg Momelotinib in an identical fashion for the bone marrow transplant experimental mouse cohort. Peripheral blood is drawn at day 14, 28, 42, and 56 and levels of red cells, white cells, reticulocytes, granulocytes, lymphocytes, and monocytes are analyzed[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.

    [2]. Monaghan KA, et al. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia, 2011, 25(12), 1891-1899.

    [3]. Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25), 5232-5240.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务

Momelotinib(Synonyms: CYT387)

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

Momelotinib (Synonyms: CYT387) 纯度: 98.93%

Momelotinib (CYT387) 是 ATP 竞争性的 JAK1/JAK2 抑制剂,IC50 值分别为 11 nM/18 nM,是对 JAK3 选择性的 10 倍左右。

Momelotinib(Synonyms: CYT387)

Momelotinib Chemical Structure

CAS No. : 1056634-68-4

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ¥935 In-stock
5 mg ¥850 In-stock
10 mg ¥1100 In-stock
50 mg ¥3000 In-stock
100 mg ¥5500 In-stock
200 mg ¥7900 In-stock
500 mg   询价  
1 g   询价  

* Please select Quantity before adding items.

Momelotinib 相关产品

相关化合物库:

  • Drug Repurposing Compound Library Plus
  • Clinical Compound Library Plus
  • Bioactive Compound Library Plus
  • Apoptosis Compound Library
  • Epigenetics Compound Library
  • Immunology/Inflammation Compound Library
  • JAK/STAT Compound Library
  • Kinase Inhibitor Library
  • Stem Cell Signaling Compound Library
  • Anti-Cancer Compound Library
  • Clinical Compound Library
  • Autophagy Compound Library
  • Anti-Aging Compound Library
  • Drug Repurposing Compound Library
  • Differentiation Inducing Compound Library
  • Reprogramming Compound Library
  • Anti-COVID-19 Compound Library
  • Anti-Breast Cancer Compound Library
  • Anti-Lung Cancer Compound Library
  • Anti-Pancreatic Cancer Compound Library
  • Anti-Blood Cancer Compound Library
  • Anti-Liver Cancer Compound Library
  • Rare Diseases Drug Library

生物活性

Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50a of 11 nM and 18 nM,respectively. CYT387 shows much less activity against JAK3.

IC50 & Target[1]

JAK1

11 nM (IC50)

JAK2

18 nM (IC50)

JAK3

155 nM (IC50)

体外研究
(In Vitro)

Momelotinib (CYT387) inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, Momelotinib (CYT387) also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, Momelotinib (CYT387) has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2 μM-4 μM[1]. Momelotinib (CYT387) inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, Momelotinib (CYT387) induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies PS-341 and L-PAM in primary multiple myeloma (MM) cells[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

In a murine MPN model, Momelotinib (CYT387) normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

414.46

Formula

C23H22N6O2

CAS 号

1056634-68-4

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : ≥ 40 mg/mL (96.51 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.4128 mL 12.0639 mL 24.1278 mL
5 mM 0.4826 mL 2.4128 mL 4.8256 mL
10 mM 0.2413 mL 1.2064 mL 2.4128 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (6.03 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (6.03 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.

    [2]. Monaghan KA, et al. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia, 2011, 25(12), 1891-1899.

    [3]. Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25), 5232-5240.

    [4]. Kitajima S, et al.Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS.Cancer Cell. 2018 Sep 10;34(3):439-452.e6. doi: 10.1016/j.ccell.2018.08.009.

Kinase Assay
[1]

Glutathione-S-transferase (GST)-tagged JAK kinase domains expressed in insect cells are purified before use in a peptide substrate phosphorylation assay. Assays are carried out in 384-well optiplates using an Alphascreen Protein Tyrosine Kinase P100 detection kit and a PerkinElmer Fusion Alpha instrument.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

Ba/F3 cells expressing JAK2V617F (Ba/F3-JAK2V617F) and MPLW515L (Ba/F3-MPLW515L) mutants, as well as CHRF-288-11 (JAK2T875N) and CMK (JAK3A572V) cells are used. The TEL/JAK2 and TEL/JAK3 fusions are generated and introduced into Ba/F3 murine cells. The TEL/JAK2- or TEL/JAK3-transfected cells are cultured in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% fetal calf serum (FCS). Ba/F3 wild-type cells are cultured in RPMI containing 10% FCS supplemented with 5 ng/mL murine IL-3. Proliferation is measured using the Alamar Blue assay after incubating for 72 hours at 37°C with 5% CO2.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[3]

On day 32 after bone marrow transplantation (when all mice exhibit severe leukocytosis and erythrocytosis), mice are assigned to 3 groups such that each group had equivalent average body weight and blood counts. Momelotinib (CYT387) is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone). Subsequently, the CYT387/NMP mix is diluted with 0.14 M Captisol to a concentration of 6 mg/mL and further diluted with 0.1M Captisol to a final concentration of 4 mg/mL. All 3 groups of mice (n=12 per group) are administered Momelotinib (CYT387) by oral gavage twice daily at 10- to 12-hour intervals from day 34 after bone marrow transplantation to day 82 (end of experiment). Mice receive NMP/Captisol without Momelotinib (CYT387) (0 mg/kg group), 25 mg/kg Momelotinib (CYT387), or 50 mg/kg Momelotinib (CYT387). At day 82 after bone marrow transplantation, all mice are euthanized for analysis except for 2 mice each from the 50 mg/kg and 25 mg/kg groups, which are taken off Momelotinib (CYT387) treatment and followed for 45 additional days. For assessment of the effects of CYT387 on normal blood counts, naive Balb/c mice are administered vehicle control, 50 mg/kg, or 100 mg/kg Momelotinib (CYT387) in an identical fashion as described for the bone marrow transplant experimental mouse cohort. Peripheral blood is drawn at day 14, 28, 42, and 56 and levels of red cells, white cells, reticulocytes, granulocytes, lymphocytes, and monocytes are analyzed[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.

    [2]. Monaghan KA, et al. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia, 2011, 25(12), 1891-1899.

    [3]. Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25), 5232-5240.

    [4]. Kitajima S, et al.Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS.Cancer Cell. 2018 Sep 10;34(3):439-452.e6. doi: 10.1016/j.ccell.2018.08.009.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务