规格 | 价格 | |
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100mg | ||
250mg | ||
500mg |
体外研究 (In Vitro) |
JDQ-443的IC50值分别为0.018和0.063 μM,可增强KRASG12C突变细胞系NCI-H358和NCI-H2122的增殖,同时还促进磷酸化ERK (pERK)水平的剂量依赖性下降[2]。 JDQ443 具有低可逆结合亲和力,可选择性地共价结合 RAS 开关 II 的口袋,抑制 GDP 结合 KRASG12C。这导致 KRAS G12C/H95、G12C/R68S 和 G12C/Y96 双突变细胞系以及 KRASG12C 突变体的再生受到可调抑制[2]。
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体内研究 (In Vivo) |
JDQ443(10-100 mg/kg,肿瘤,每天,持续 14 天)在 KRAS G12C 突变 CDX 模型中以剂量依赖性方式表现出抗活性并抑制肿瘤生长 [2]。 JDQ443(侧壁,100 mg/kg),每日(JDQ443)+ 7.5 mg/kg,每日两次(TNO155),持续36天)与单药JDQ443联合使用时表现出更好的细胞生长抑制或细胞杀伤作用[2]。肿瘤耐药性分类是在 NSCLC 和结直肠癌的 PDX 模型中创建的,并通过各种药物的联合治疗得到增强 [2]。
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参考文献 |
[1]. LIU BO, et al. PYRAZOLYL DERIVATIVES USEFUL AS ANTI-CANCER AGENTS. Patent WO2021120890A1.
[2]. Weiss A, Lorthiois E, Barys L, et al. Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent and Selective, Covalent Oral Inhibitor of KRASG12C. Cancer Discov. 2022;candisc.0158.2022. |
分子式 |
C29H28CLN7O
|
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分子量 |
526.03
|
精确质量 |
525.2043862
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CAS号 |
2653994-10-4
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相关CAS号 |
Opnurasib;2653994-08-0
|
外观&性状 |
solid
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SMILES |
CC1=CC2=C(C=NN2)C(=C1Cl)C3=C(N(N=C3C4=CC5=C(C=C4)N(N=C5)C)C6CC7(C6)CN(C7)C(=O)C=C)C
|
InChi Key |
AZUYLZMQTIKGSC-UHFFFAOYSA-N
|
InChi Code |
InChI=1S/C29H28ClN7O/c1-5-24(38)36-14-29(15-36)10-20(11-29)37-17(3)25(26-21-13-31-33-22(21)8-16(2)27(26)30)28(34-37)18-6-7-23-19(9-18)12-32-35(23)4/h5-9,12-13,20H,1,10-11,14-15H2,2-4H3,(H,31,33)
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化学名 |
1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one
|
别名 |
(S)-NVP-JDQ443; (S)-JDQ-443
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体内) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 请根据您的实验动物和给药方式选择适当的溶解配方/方案: 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。 |
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制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9010 mL | 9.5052 mL | 19.0103 mL | |
5 mM | 0.3802 mL | 1.9010 mL | 3.8021 mL | |
10 mM | 0.1901 mL | 0.9505 mL | 1.9010 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) 。
JDQ443 has selective activity for KRASG12C, including H95 double mutants, and shows dose-dependent single-dose pharmacokinetics and pharmacodynamics in mouse tumor models. Cancer Discov . 2022 Jun 2;12(6):1500-1517. td> |
JDQ443 displays antitumor activity across a range of cell-derived, KRASG12C-dependent mouse tumor models, with efficacy driven by daily AUC. Cancer Discov . 2022 Jun 2;12(6):1500-1517. td> |
JDQ443 generates categorical antitumor responses in PDX models of NSCLC and colorectal tumors that are improved by combination treatment with other agents. Cancer Discov . 2022 Jun 2;12(6):1500-1517. td> |
JDQ443 plus TNO155 improves the single-agent activity of JDQ443 in CDX models, with efficacy maintained with lower doses of either drug. Cancer Discov . 2022 Jun 2;12(6):1500-1517. td> |