规格 | 价格 | 库存 | 数量 |
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5mg |
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10mg |
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50mg |
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100mg |
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Other Sizes |
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靶点 |
GADD45β/MKK7
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体外研究 (In Vitro) |
DTP3(10 μM;1-21 天)会导致磷酸化 JNK 的发育最早在强烈且肿瘤特异性的 JNK 激活和凋亡诱导后 24 小时出现[2]。
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体内研究 (In Vivo) |
DTP3 TFA(皮下注射;14.5 毫克/公斤/天;28 天)基本上消除了小鼠皮下骨髓瘤异种移植物,并显示出显着的肿瘤缩小[2]。 DTP3 TFA(静脉注射;10 mg/kg/天)的t1/2、CL和Vd值分别为1.26小时、27.13 ML/min/kg和2.80 L/kg[2]。
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细胞实验 |
蛋白质印迹分析[2]
细胞类型: 多发性骨髓瘤 (MM) 细胞系 测试浓度: 10 μM 孵育时间: 1、3、5、14、21天 实验结果:早在24小时就引起了磷酸化JNK的出现。 |
动物实验 |
Animal/Disease Models: 6 to 8-week old male NOD/SCID (severe combined immunodeficient) mouse (NOD.CB17-Prkdcscid/IcrCrl; Charles River)[2]
Doses: 14.5 mg/kg Route of Administration: Sc; daily; 28 days Experimental Results: Had shown a dramatic shrinkage of the tumors. Animal/Disease Models: CD1 male mice of 25-30 g[2] Doses: 10 mg/kg (pharmacokinetic/PK Study) Route of Administration: intravenous (iv)injection Experimental Results: Had t1/2 of 1.26 hrs (hours), CL of 27.13 ML/min/kg, and Vd of 2.80 L/kg. |
参考文献 |
[1]. Tornatore L, et al. Preclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7inhibitor and clinical candidate, DTP3. Toxicol Rep. 2019 Apr 19;6:369-379.
[2]. Tornatore L, et al. Cancer-selective targeting of the NF-κB survival pathway with GADD45β/MKK7 inhibitors. Cancer Cell. 2014 Oct 13;26(4):495-508. |
分子式 |
C28H36F3N7O7
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分子量 |
639.62
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精确质量 |
639.26
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CAS号 |
2759216-46-9
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相关CAS号 |
DTP3;1809784-29-9
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外观&性状 |
Powder
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SMILES |
CC(=O)N[C@H](CC1=CC=C(C=C1)O)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CC2=CC=CC=C2)C(=O)N.C(=O)(C(F)(F)F)O
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InChi Key |
JCVMRDQSOXBZIO-AFYLVLOISA-N
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InChi Code |
InChI=1S/C26H35N7O5.C2HF3O2/c1-16(34)31-22(15-18-9-11-19(35)12-10-18)25(38)32-20(8-5-13-30-26(28)29)24(37)33-21(23(27)36)14-17-6-3-2-4-7-17;3-2(4,5)1(6)7/h2-4,6-7,9-12,20-22,35H,5,8,13-15H2,1H3,(H2,27,36)(H,31,34)(H,32,38)(H,33,37)(H4,28,29,30);(H,6,7)/t20-,21-,22-;/m1./s1
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化学名 |
(2R)-2-[[(2R)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-N-[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)pentanamide;2,2,2-trifluoroacetic acid
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别名 |
DTP3 TFA
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溶解度 (体外) |
H2O : ~100 mg/mL (~156.3 mM)
DMSO : ~50 mg/mL (~78.2 mM) |
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溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (156.34 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 1.5634 mL | 7.8171 mL | 15.6343 mL | |
5 mM | 0.3127 mL | 1.5634 mL | 3.1269 mL | |
10 mM | 0.1563 mL | 0.7817 mL | 1.5634 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
计算结果:
工作液浓度: mg/mL;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
The secondary pharmacology and drug-drug interaction potential of DTP3. Toxicol Rep . 2019 Apr 19:6:369-379. td> |
The safety pharmacology of DTP3. Toxicol Rep . 2019 Apr 19:6:369-379. td> |
The PK and ADME profiles of DTP3. Toxicol Rep . 2019 Apr 19:6:369-379. td> |
The therapeutic efficacy of DTP3 in a mouse MM xenograft model upon intravenous bolus injection by a clinically suitable dosing schedule. Toxicol Rep . 2019 Apr 19:6:369-379. td> |
The High Target Specificity of DTP3 in Cells. Cancer Cell . 2014 Oct 13;26(4):495-508 td> |
The Potent Activity of DTP3 in Primary MM Cells and Its Far Superior Cancer Cell Selectivity Compared with IKKβ and Proteasome Inhibitors. Cancer Cell . 2014 Oct 13;26(4):495-508. td> |
DTP3 Exhibits Potent Therapeutic Activity against MM, In Vivo, in the Absence of Any Apparent Side Effects. Cancer Cell . 2014 Oct 13;26(4):495-508. td> |