Talabostat mesylate
(Synonyms: [(2R)-1-[(2S)-2-氨基-3-甲基丁酰基]吡咯烷-2-基]硼酸甲磺酸盐,Val-boroPro mesylate; PT100 mesylate) 目录号 : GC10018
塔拉司他Talabostat (PT100)是二肽基肽酶DPP的抑制剂，对DPP-IV、DPP8、DPP9、QPP、FAP和PEP的IC50值分别为<4 nM、4 nM、11 nM、310 nM、560 nM和390 nM。它具有抗肿瘤和刺激造血作用的活性。
Cas No.:150080-09-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment [1]: |
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Cell lines |
THP-1 cells, RAW 264.7 and J774 cells |
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Preparation method |
THP-1 cells were differentiated in 10 cm dishes in complete medium with 50 ng/mL PMA for 3 d. RAW 264.7 and J774 cells were plated at 3 × 106 cells per 10 cm plate in complete medium and incubated overnight. The cells were washed with 2 × 5 mL PBS before the addition of 10 mL of serum free media. Cells were then treated with Talabostat (PT100) (2 μM) or LPS (10 μg/mL) for 24 h. |
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Reaction Conditions |
2 μM; 24 h |
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Applications |
Talabostat (PT100) induces an active form of pro-caspase-1 that can sufficiently cleave a substrate (or substrates) that mediates pyroptosis, but that does not efficiently cleave IL-1β or the tetrapeptide Ac-WEHD-AFC. |
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Animal experiment [2]: |
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Animal models |
BALB/c, C56BL/6, DBA/2, and BALB/cnu/nu mice |
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Preparation method |
Tumor-inoculated mice were given varying doses (5–40 μg) of Talabostat(PT100) or saline vehicle by oral gavage, twice daily at ∼8h intervals. The time of tumor inoculation was defined as day 0, and PT-100 treatment was started on either day 2 or day 7 and continued daily. |
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Dosage form |
5–40 μg twice daily at ∼8h intervals；p.o. |
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Applications |
Treatment with Talabostat(PT100) was found to significantly inhibit the additional growth of B16-F10, WEHI 164 and EL 4 tumor cells in mice. |
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References: [1] Okondo M C , Johnson D C , Sridharan R ,et al.DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis[J].Nature Chemical Biology, 2017 Jan; 13(1): 46–53. [2] Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. |
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Talabostat (PT100) is an orally active and non-selective inhibitor of dipeptidyl peptidase IV (DPP-IV) (IC50 < 4 nM; Ki = 0.18 nM) and the first clinical inhibitor of fibroblast activation protein (FAP) (IC50= 560 nM), inhibiting DPP 8/9 (IC50= 4/11 nM; Ki = 1.5/0.76 nM), prolyl endopeptidase (QPP) (IC50= 310 nM), DPP2, and other DASH family enzymes[1]. Due to its inhibitory action on these proteases, the mechanism of action of Talabostat (PT100) involves the inhibition of protease activity, thereby affecting the tumor microenvironment, immune cell activity, and inflammatory responses[2]. Talabostat (PT100) is also known to stimulate hematopoiesis.
In vitro, Talabostat (PT100) at concentrations ranging from 30 pg/ml to 30 μg/ml when added to the culture medium, can induce tumor regression and rejection in WEHI 164 fibrosarcoma and EL 4 and A20/2 J lymphoma models[1]. Talabostat (PT100) (2μM, 24h) can induce the active form of caspase-1, which can efficiently cleave substrates mediating pyroptosis but not effectively cleave IL-1β or the tetrapeptide Ac-WEHD-AFC[4]. In tumors and tumor-draining lymph nodes, Talabostat (PT100) stimulates the transcriptional upregulation of various cytokines such as IL-1β, IL-6, G-CSF, and CXCL1/KC[4].
In vivo, Talabostat (PT100) significantly inhibits the extraneous growth of tumors such as B16-F10, WEHI 164, and EL 4 tumor cells in mice through delayed oral administration (5–40 μg, twice daily, approximately 8 hours apart) [3].
References:
[1] Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13.
[2] Lankas GR, et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes. 2005 Oct;54(10):2988-94.
[3] Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80.
[4] Okondo M C , Johnson D C , Sridharan R ,et al.DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis[J].Nature Chemical Biology, 2017 Jan; 13(1): 46–53.
Talabostat (PT100)是一种口服活性和非选择性二肽基肽酶IV（DPP-IV）抑制剂(IC50 < 4 nM; Ki = 0.18 nM)和成纤维细胞活化蛋白(FAP)的第一种临床抑制剂(IC50 = 560 nM)，抑制DPP 8/9(IC50= 4/11 nM; Ki = 1.5/0.76 nM)，静止细胞脯氨酸二肽酶(QPP)( IC50= 310 nM)，DPP 2和其他一些DASH家族酶[1]。由于其对这些蛋白酶的抑制作用，Talabostat (PT100)的作用机制涉及抑制蛋白酶活性，进而影响肿瘤微环境、免疫细胞活性以及炎症反应[2]。Talabostat (PT100)还可作用于刺激造血。
在体外，Talabostat (PT100)以30 pg/ml至30 μg/ml的浓度加入培养基中，在WEHI 164纤维肉瘤和EL 4和A20/2 J淋巴瘤模型中可引起肿瘤消退和排斥[3]。Talabostat (PT100) (2μM, 24h) 可以诱导活性形式的胱天蛋白酶原-1，其可以充分切割介导焦亡的底物，但不能有效切割IL-1β或四肽Ac-WEHD-AFC[4]。在肿瘤和肿瘤引流淋巴结中，Talabostat (PT100)可刺激多种细胞因子的转录上调，如IL-1β、IL-6、G-CSF和CXCL1/KC[4]。
在体内，Talabostat (PT100)通过延迟口服施用(5–40 μg，每日两次，间隔约8小时)，在接种有B16-F10、WEHI 164和EL 4肿瘤细胞的小鼠中，显著抑制了这些肿瘤的额外生长[3]。
| Cas No. | 150080-09-4 | SDF | |
| 别名 | [(2R)-1-[(2S)-2-氨基-3-甲基丁酰基]吡咯烷-2-基]硼酸甲磺酸盐,Val-boroPro mesylate; PT100 mesylate | ||
| Canonical SMILES | OS(=O)(C)=O.O=C([C@H](C(C)C)N)N1[C@H](B(O)O)CCC1 | ||
| 分子式 | C10H23BN2O6S | 分子量 | 310.18 |
| 溶解度 | ≥ 11.45mg/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 | 3.2239 mL | 16.1197 mL | 32.2393 mL |
| 5 mM | 0.6448 mL | 3.2239 mL | 6.4479 mL |
| 10 mM | 0.3224 mL | 1.612 mL | 3.2239 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。