Bisindolylmaleimide I (GF109203X) is a highly selective, cell-permeable, and reversible protein kinase C (PKC) inhibitor with a K_i of 14 nM.

Bisindolylmaleimide I is a competitive inhibitor with respect to ATP (K_i=14 nM) and displays high selectivity for PKC as compared to five different protein kinases. GF 109203X efficiently prevents PKC-mediated phosphorylations of an M_r=47,000 protein in platelets and of an M_r=80,000 protein in Swiss 3T3 cells. GF 109203X inhibits collagen- and a-thrombin-induced platelet aggregation as well as collagen-triggered ATP secretion. However, ADP-dependent reversible aggregation is not modified. In Swiss 3T3 fibroblasts, GF 109203X reverses the inhibition of epidermal growth factor binding induced by phorbol 12,13-dibutyrate and prevents [³H] thymidine incorporation into DNA, only when this is elicited by growth promoting agents which activate PKC^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Pial arteriole diameter changes are monitored using a closed cranial window in vivo microscopy technique. The pial arteriole dilatory response associated with SNS is decreased by 45%, when comparing DM vs either ND or TR rats. Also, pial arteriolar dilations to topical KCl and NS1619 are largely attenuated in DM rats, but not in ND or TR animals. These responses are completely restored by the acute application of Bisindolylmaleimide I to the brain surface. The PKC inhibitor has no effect on vascular responses in normoglycemic and TR animals. In conclusion, DM-associated chronic impairment of neurovascular coupling may be readily reversed by a PKC-α/β/γ inhibitor or prevented via pancreatic islet transplantation. Specific PCK isoforms (α/β/γ) are believed to be mechanistically linked to the neurovascular uncoupling seen with hyperglycemia^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

412.48

C₂₅H₂₄N₄O₂

133052-90-1

Room temperature in continental US; may vary elsewhere.

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

In Vitro: 

DMSO : ≥ 32 mg/mL (77.58 mM)

* “≥” means soluble, but saturation unknown.

*

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, 6 months; -20°C, 1 month (protect from light)。-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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 1 mg/mL (2.42 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (2.42 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• [1]. Toullec D, et al. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991 Aug 25;266(24):15771-81.

  [2]. Vetri F, et al. Impairment of neurovascular coupling in Type 1 Diabetes Mellitus in rats is prevented by pancreatic islet transplantation and reversed by a semi-selective PKC inhibitor. Brain Res. 2017 Jan 15;1655:48-54.

Assay of PKC is arrayed by measuring ³²Pi transferred from [γ-³²Pi] ATP to lysine-rich histone type Ill-s. The reaction mixture (80 μL) contains 50 mM Tris-HCI, pH 7.4. 100 μM CaCl₂, 10 mM MgCI₂, 37.5 μg/mL histone type Ill-s, l0 μM [γ-³²Pi] ATP (1250cpm/pmol), 31 μM bovine brain phosphatidylserine and 0.5 μM 1,2 sn-dioleylglycerol. 15 μL of purified PKC (final concentration in assay 0.38 μg/mL) is added to the incubation mixture. After 10 minutes, the reaction is stopped by addition of at 30 μL of casein 30 mg/mL and 0.9 mL of 12% trichlomacetic acid^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Three sets of Lewis rats is used for this study: 1) euglycemic 4–6 month old non-diabetic controls (ND group, n=11); 2) streptozotocin (STZ)-treated diabetic rats (6 month old, 4 months post-STZ) (DM group, n=6); and 3) STZ-treated diabetic animals, subjected to pancreatic islet transplantation soon after the establishment of the diabetic model, studied 100–110 days after the transplant (TR group, n=7)^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Toullec D, et al. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991 Aug 25;266(24):15771-81.

  [2]. Vetri F, et al. Impairment of neurovascular coupling in Type 1 Diabetes Mellitus in rats is prevented by pancreatic islet transplantation and reversed by a semi-selective PKC inhibitor. Brain Res. 2017 Jan 15;1655:48-54.