TC LPA5 4是一种强效的LPA5选择性受体拮抗剂和heparanase（乙酰肝素酶）抑制剂，IC50值分别为0.8μM和10μM。
Cas No.:1393814-38-4
Sample solution is provided at 25 µL, 10mM.
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TC LPA5 4 is a potent LPA5-selective receptor antagonist and a heparanase inhibitor with IC50 values of 0.8μM and 10μM, respectively[1]. TC LPA5 4 can enhance anti-tumor activity and inhibit metastasis by inhibiting LPAR5 and autotaxin in immune cell types[2]. TC LPA5 4 has been widely used in the development of combined therapies to inhibit the progression of multiple myeloma[3].
In vitro, TC LPA5 4 treatment at 1μM for 3 days at a 21% oxygen concentration significantly promoted the growth of DLD-1 cells[4]. The 4-hour treatment with 1μM TC LPA5 4 significantly reduced the maximum respiratory capacity enhancement of LPA-mediated effector CD8 T cells, without affecting the basal respiratory capacity[5]. Treatment of 0.5μM TC LPA5 4 for 16 hours significantly stimulated the motility of HT1080 cells[6].
In vivo, TC LPA5 4 treatment via intraperitoneal injection at a doe of 10mg/kg (5 times a week) for 2 weeks significantly inhibited CGTH‐W3 xenograft growth in mice[7].
References:
[1] Zhang Y, Xiong M, Chen Z, et al. Design principle of heparanase inhibitors: A combined in vitro and in silico study[J]. ACS Medicinal Chemistry Letters, 2024, 15(7): 1032-1040.
[2] Lee S C, Dacheux M A, Norman D D, et al. Regulation of tumor immunity by lysophosphatidic acid[J]. Cancers, 2020, 12(5): 1202.
[3] Zhou X, Yang Y, Hu X, et al. Identification of LPAR1/LPAR5 as novel GPCR partners of GPRC5D for the efficient CAR-T therapy of multiple myeloma[J]. Blood, 2023, 142: 4679.
[4] Yamamoto M, Takai M, Yashiro N, et al. The role of LPA receptor signaling in modulating cellular responses of colon cancer cells co-cultured with lymphoid endothelial cells under hypoxic stress[J]. Tissue and Cell, 2024, 91: 102528.
[5] Turner J A, Fredrickson M A, D’Antonio M, et al. Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity[J]. Nature Communications, 2023, 14(1): 3214.
[6] Takahashi K, Minami K, Otagaki S, et al. Lysophosphatidic acid receptor-2 (LPA2) and LPA5 regulate cellular functions during tumor progression in fibrosarcoma HT1080 cells[J]. Biochemical and biophysical research communications, 2018, 503(4): 2698-2703.
[7] Zhao W J, Zhu L L, Yang W Q, et al. LPAR5 promotes thyroid carcinoma cell proliferation and migration by activating class IA PI3K catalytic subunit p110β[J]. Cancer Science, 2021, 112(4): 1624-1632.
TC LPA5 4是一种强效的LPA5选择性受体拮抗剂和heparanase（乙酰肝素酶）抑制剂，IC50值分别为0.8μM和10μM[1]。TC LPA5 4通过抑制免疫细胞类型中的LPAR5和自分泌运动因子，能够增强抗肿瘤活性并抑制转移[2]。TC LPA5 4已被广泛用于开发抑制多发性骨髓瘤进展的联合疗法[3]。
在体外，在21%氧气浓度下，使用1μM的TC LPA5 4处理DLD-1细胞3天，显著促进了细胞生长[4]。用1μM的TC LPA5 4处理效应CD8 T细胞4小时，显著降低了LPA介导的最大呼吸能力增强，不影响基础呼吸能力[5]。使用0.5μM的TC LPA5 4处理HT1080细胞16小时，显著刺激了细胞运动[6]。
在体内，通过腹腔注射TC LPA5 4，剂量为10mg/kg（每周5次），持续2周，显著抑制了小鼠体内CGTH‐W3异种移植瘤的生长[7]。
| Cell experiment [1]: | |
Cell lines | DLD-1 cells |
Preparation Method | DLD-1 cells were seeded at a density of 3000 cells per well into the wells of 96-well plates and cultured in 5 % fetal bovine serum (FBS)-DMEM medium under 21 % and 1 % O2 conditions for 3 days. Cells were treated with LPA (1μM) for 30min, followed by treatment with AM966 and TC LPA5 4 at concentrations of 0, 0.1 and 1μM, respectively for 3 days. Then, the cell viability was analyzed. |
Reaction Conditions | 0, 0.1 and 1μM; 3 days |
Applications | TC LPA5 4 treatment significantly enhanced the cell viability of DLD-1 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | BALB/C-nu/nu mice |
Preparation Method | BALB/C-nu/nu mice, aged 4-5 weeks, were housed in sterile cages under laminar airflow hoods in a specific pathogen‐free room with a 12‐hour light and 12‐hour dark schedule. The mice were fed autoclaved chow and water ad libitum. A total of 1×107 CGTH-W3 cells were transplanted s.c. into the flank of the nude mice. When the tumor volume reached 100mm3, the mice were randomly assigned into control and treatment groups. Control groups were given vehicle, and treatment groups received TC LPA5 4 administration (10mg/kg; i.p.) 5 times a week for 2 weeks. The sizes of the tumors were measured twice per week. |
Dosage form | 10mg/kg; 5 times a week for 2 weeks; i.p. |
Applications | TC LPA5 4 treatment significantly inhibited CGTH‐W3 xenograft growth in mice. |
References: | |
| Cas No. | 1393814-38-4 | SDF | |
| 化学名 | 5-(3-chloro-4-cyclohexylphenyl)-1-(3-methoxyphenyl)-1H-pyrazole-3-carboxylic acid | ||
| Canonical SMILES | COC1=CC=CC(N2C(C3=CC(Cl)=C(C4CCCCC4)C=C3)=CC(C(O)=O)=N2)=C1 | ||
| 分子式 | C23H23ClN2O3 | 分子量 | 410.89 |
| 溶解度 | <41.09mg/ml in DMSO | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4337 mL | 12.1687 mL | 24.3374 mL |
| 5 mM | 486.7 μL | 2.4337 mL | 4.8675 mL |
| 10 mM | 243.4 μL | 1.2169 mL | 2.4337 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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