GGTI 2133是一种高度选择性的肽模拟型GG转移酶I（PGGTase-I）抑制剂，其对PGGTase-I和法尼基转移酶（FTase）的IC₅₀值分别为38nM和5.4μM，对PGGTase-I表现出约140倍的选择性。
Cas No.:191102-79-1
Sample solution is provided at 25 µL, 10mM.
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GGTI 2133 is a highly selective peptidomimetic inhibitor of geranylgeranyl transferase type I (PGGTase-I), with IC₅₀ values of 38nM and 5.4μM for PGGTase-I and farnesyl transferase (FTase), respectively, indicating 140-fold selectivity[1].
In vitro, GGTI 2133 inhibited Rap1A processing in NIH3T3 cells with an IC₅₀ of 10μM, but had no effect on H-Ras processing, with an IC₅₀ exceeding 30μM[1]. Incubation with 10μM GGTI 2133 for 28h reduced CD4⁺T cell expansion but not CD8⁺T cell expansion, and inhibited ERK1/2 phosphorylation in T cells stimulated with CD3/CD28 beads[2].
In vivo, in male BALB/c mice with allergic bronchial asthma, once-daily intraperitoneal administration of GGTI 2133 (5mg/kg/day) for 10 days alleviated eosinophilic airway inflammation, primarily by inhibiting eosinophil infiltration into the airways[3].
References:
[1] Vasudevan A, Qian Y, Vogt A, et al. Potent, highly selective, and non-thiol inhibitors of protein geranylgeranyltransferase-I. J Med Chem. 1999;42(8):1333-1340.
[2] Hechinger AK, Maas K, Dürr C, et al. Inhibition of protein geranylgeranylation and farnesylation protects against graft-versus-host disease via effects on CD4 effector T cells. Haematologica. 2013;98(1):31-40.
[3] Chiba Y, Sato S, Misawa M. GGTI-2133, an inhibitor of geranylgeranyltransferase, inhibits infiltration of inflammatory cells into airways in mouse experimental asthma. Int J Immunopathol Pharmacol. 2009;22(4):929-935.
GGTI 2133是一种高度选择性的肽模拟型GG转移酶I（PGGTase-I）抑制剂，其对PGGTase-I和法尼基转移酶（FTase）的IC₅₀值分别为38nM和5.4μM，对PGGTase-I表现出约140倍的选择性[1]。
体外实验中，GGTI 2133在NIH3T3细胞中抑制Rap1A的加工，其IC₅₀值为10μM，但对H-Ras的加工无影响，其IC₅₀值超过30μM[1]。用10μM GGTI 2133孵育28h可减少CD4⁺T细胞的扩增，但对CD8⁺T细胞的扩增无明显影响，同时可抑制CD3/CD28球粒刺激的T细胞中ERK1/2的磷酸化水平[2]。
体内实验中，在患有过敏性支气管哮喘的雄性BALB/c小鼠中，每日一次腹腔注射GGTI 2133（5mg/kg/day），连续10天，可改善嗜酸性气道炎症，主要表现为抑制嗜酸性粒细胞向气道的浸润[3]。
| Cell experiment [1]: | |
Cell lines | NIH3T3 |
Preparation Method | Cells were treated on each of two successive days with 1 and 10μM GGTI 2133, then harvested, and subjected to western blot analysis to demonstrate the inhibition of geranylgeranylated Rap1A or farnesylated H-Ras. |
Reaction Conditions | 1 and 10μM; 2d |
Applications | GGTI 2133 inhibited Rap1A processing in cells with an IC₅₀ of 10μM, while having no effect on H-Ras processing, with an IC₅₀ greater than 30μM. |
| Animal experiment [2]: | |
Animal models | Male BALB/c mice with allergic bronchial asthma |
Preparation Method | Mice were actively sensitized by intraperitoneal injections of 8ug ovalbumin with 2mg Imject Alum on days 0 and 5. The sensitized mice were challenged with aerosolized OA saline solution (5mg/mL) for 30min on days 12, 16 and 20. A control group of mice received the same immunization procedure but inhaled saline aerosol instead of OA challenge. Animals also received intraperitoneal injection with GGTI 2133 (5mg/kg/day) or its vehicle once a day for 10 days from Day 11 to Day 20. The treatment was carried out 1h before the antigen inhalation on the respective days ofthe antigen challenge (Days 12, 16 and 20). 24h after the last OA challenge, cells in bronchoalveolar lavage (BAL) fluid were counted, and the levels of interleukin (IL)-4, IL-13, eotaxin, thymosin, thymus and activation-regulated chemokine (TARC), and leukotriene B4 (LTB4) were measured. |
Dosage form | 5mg/kg/d; 10d; i.p. |
Applications | Both the increases in eosinophils and lymphocytes induced by the repeated antigen exposure were significantly reduced by the systemic treatments with GGTI 2133. GGTI 2133 had no effect on the antigen-induced upregulation of IL-4, IL-13, eotaxin, TARe, or LTB4 in BAL fluids. |
References: | |
| Cas No. | 191102-79-1 | SDF | |
| 化学名 | N-[4-[(1H-imidazol-5-ylmethyl)amino]-2-(1-naphthalenyl)benzoyl]-L-leucine | ||
| Canonical SMILES | O=C(N[C@H](C(O)=O)CC(C)C)C1=CC=C(NCC2=CNC=N2)C=C1C3=C4C(C=CC=C4)=CC=C3 | ||
| 分子式 | C27H28N4O3 | 分子量 | 456.5 |
| 溶解度 | DMSO : 100 mg/mL (219.04 mM; Need ultrasonic) | 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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| 1 mM | 2.1906 mL | 10.9529 mL | 21.9058 mL |
| 5 mM | 438.1 μL | 2.1906 mL | 4.3812 mL |
| 10 mM | 219.1 μL | 1.0953 mL | 2.1906 mL |
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