Motolimod (VTX-2337)
(Synonyms: VTX-2337; VTX-378) 目录号 : GC11168
A TLR8 agonist
Cas No.:926927-61-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Kinase experiment: |
Human embryonic kidney cells (HEK293) expressing TLR2, 3, 4, 5, 7, 8, or 9 are cultured in Dulbecco's Modified Eagle's Media containing 4.5 g/L L-glucose and 10% FBS. The activity of specific TLR agonists is assessed using the secretory embryonic alkaline phosphatase (SEAP) reporter gene that is linked to NF-κB activation in response to TLR stimulation. Measurement of SEAP activity using the Quanti-blue substrate after TLR agonist treatment is carried out similarly[1]. |
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Cell experiment: |
PBMCs or purified NK cells are prepared, and the purity of NK cells is approximately 99%. NK cell-mediated cytotoxicity is assessed by Calcein AM release from labeled target cells. In brief, PBMCs or purified NK cells are cultured for 48 hours in RPMI medium in the presence of Motolimod (167 or 500 nM) before incubation with target cells[1]. |
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Animal experiment: |
Monkeys[2] The male monkeys (2.9-4.9 kg) are housed individually (cage dimensions of 0.76 m wide×0.74 m deep×0.81 m in height), but commingled periodically as part of the environmental enrichment program. The animals are also given fruit, vegetable, or additional supplements as a form of environmental enrichment, as well as given various cage enrichment devices. Animals are given Certified Primate Diet, two times daily and water ad libitum. Motolimod is administered as a bolus subcutaneous (SC) injection in the intrascapular area at doses of 1 and 10 mg/kg. Blood samples are collected at baseline (pre-dose), and 6, 12, 24, and 96 h post injection to monitor levels of IL-1β and IL-18 in the plasma using the human MAP v.1.6 inflammation panel. |
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References: [1]. Lu H, et al. VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin Cancer Res. 2012 Jan 15;18(2):499-509. |
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Target: TLR8
IC50: 100 nM (EC50)
Motolimod (VTX-2337) is a small molecule, selective Toll-like receptor (TLR) 8 agonist with EC50 value of 100 nM [1]. VTX-2337 is currently in clinical development as an immunotherapy for multiple oncology indications, including ovarian cancer and squamous cell carcinoma of the head and neck [2]. TLR8 is located in the endosome where it functions in the recognition of foreign nucleic acids from intracellular pathogens. TLR8 has emerged as a potential target for anticancer immunotherapies [1].
In vitro: VTX-2337 (800 nmol/L) activated NK cells, leading to increased TNFα and IL-12, IFNγ production and VTX-2337 (167 or 500 nmol/L) augmented rituximab- and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) [1]. Moreover, VTX-2337 (3 or 10 μM) induced mature IL-1β and IL-18 production through NLRP3 inflammasome activation in THP-1 cells [2].
In vivo: VTX-2337 (1 or 10 mg/kg, subcutaneous injection) induced IL-1β and IL-18 production in male cynomolgus monkeys [2].
Clinical trial: In a phase I dose-finding study, VTX-2337 (0.1–3.9 mg/m2, subcutaneous administration) was well tolerated and active with a predictable pharmacologic profile in adult subjects with advanced solid tumors or lymphoma [3].
References:
1. Lu H, Dietsch GN, Matthews MA, Yang Y, Ghanekar S, Inokuma M, et al. VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin Cancer Res. 2012;18(2):499-509.
2. Dietsch GN, Lu H, Yang Y, Morishima C, Chow LQ, Disis ML, et al. Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity. PLoS One. 2016;11(2):e0148764.
3. Northfelt DW, Ramanathan RK, Cohen PA, Von Hoff DD, Weiss GJ, Dietsch GN, et al. A phase I dose-finding study of the novel Toll-like receptor 8 agonist VTX-2337 in adult subjects with advanced solid tumors or lymphoma. Clin Cancer Res. 2014;20(14):3683-91.
| Cas No. | 926927-61-9 | SDF | |
| 别名 | VTX-2337; VTX-378 | ||
| 化学名 | 2-imino-N,N-dipropyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[b]azepine-4-carboxamide | ||
| Canonical SMILES | CCCN(C(C(CC1=N)=CC2=C(N1)C=C(C3=CC=C(C(N4CCCC4)=O)C=C3)C=C2)=O)CCC | ||
| 分子式 | C28H34N4O2 | 分子量 | 458.6 |
| 溶解度 | ≥ 15.7mg/mL in DMSO, ≥ 45.8mg/mL in EtOH with ultrasonic and warming | 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 | 2.1805 mL | 10.9027 mL | 21.8055 mL |
| 5 mM | 0.4361 mL | 2.1805 mL | 4.3611 mL |
| 10 mM | 0.2181 mL | 1.0903 mL | 2.1805 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。