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A66 | PI3K Inhibitor- The Ultimate Guide For Beginners 2019

A66 PI3K Inhibitor- The Ultimate Guide For Beginners 2019

Over the years, cancer has been the leading cause of rampant deaths all across the globe. For this reason, there’s urgent need for cancer researchers and biochemical scientists to invent and upgrade to better chemotherapeutical drugs.

Presently, A66 kinase inhibitor has proved to counter cancerous cells by inhibiting the growth of tumors and metastasis. At least, several cell experiments and animal models have backed up the efficacy of the drug in managing certain carcinomas.

1.What Is A66?

A66 is a chemical with CAS 1166227-08-2.

It is a specific inhibitor of p110α, which is a critical oncogenic factor. Besides, the compound inhibits p110α/E545K and p110α/H1047R with IC50 of 30nM and 43nM, respectively. It impedes the phosphorylation of protein kinase B (PKB) at T308.

A66 works to hold back phosphoinositide 3-kinase signaling. Due to these inhibition properties, the compound has been known to bottle up the growth of tumors in some cells. So, if you need some for your oncology study, you can source it from a reliable A66 manufacturer.

Long-time treatment with A66 exhibits several effects. Firstly, the chemical cuts back on S6K phosphorylation on the Thr389 marker. When chronic insulin treatment stimulates IRS downregulation in 3T3-L1 adipocytes and C2C12 myoblasts, A66 rolls up to counteract the activity.

Several in vivo models back up the fact that A66 pI3K inhibitor shrinks down the growth of tumors on specific cell lines. In the case where persistent metabolic stress induces insulin resistance, this biochemical steps in to inhibit the action.

2. What’s the Biological Activity on A66?

A66 selectively inhibits p110α and its oncogenic isoforms with IC50 of 32nM and 43nM, respectively. The targeted isoforms include E545K and H1047R.

P110α is a subunit of class I phosphatidylinositol-4,5-biphosphate 3-kinase, consisting of a regulatory 85kDa and a catalytic 110kDa subunit. The product has a high affinity for p110α over other PI3K isoforms.

A66 PI3K inhibitor neither affects other lipid kinases nor the rest of the class-I phosphoinositide 3-kinases. A test done at 10micromolar proves that the biochemical is hundred-folds less inhibitory against 200+ protein kinases. Thanks to these exclusive properties, A-66 is among the few sought after PI3K inhibitors for research purposes.

A66 works on specific cells with high amounts of p110α and H1047R mutations in PIK3CA. The treatment inhibits phosphorylation of Akt/PKB on T308.

In xenograft study models, scholars investigate the A-66 pharmacokinetics by administering a dosage of 10mg per kilogram of bodyweight. The drug is administered to CD-1 mice through the intraperitoneal injection.

When SKOV3 (ovarian cancer cell line) is tested with a dose of about 100mg/kg, there will be a fall in the phosphorylation of protein kinase B/Akt. However, the process will not affect the extracellular-signal regulated kinase (ERK) after one and six-hour A66 injection. The levels of this drug on the tumor will be slightly higher than the amount present in the plasma. For instance, after the sixth hour, the plasma concentration falls at about 9μM while at the tumor, the level is approximately 16μM.

3.What Features on A66?

A66 is potently selective for the wild-type p100alpha isoform and its oncogenic isoforms such as E545K and H1047R. The biochemical is 100X selective for p110α as compared to the rest of the class-I PI3 isoforms. The cross-reactivity of A-66 kinase inhibitor cancer with class-II PI3K, PI4Kβ, and class-III PI3K is limited.

 

A66 PI3K Inhibitor- The Ultimate Guide For Beginners 2019

 

A66 has no inhibitory effects on the other lipid kinases, DNA-PK, or mTOR. The compound is more specific than PIK-75, when it’s tested against 318 kinases and 110 protein kinases.

4.What Research is being done on A66?

For Cell Experiment

The targeted cell lines are the CD+ T lymphocytes. These cells are isolated, activated by centrifugation, lysis of the red blood cells, and washing in a culture medium.

The naive CD4+ T cells are isolated using the Miltenyi CD4+CD62L+ T cell isolation kit II for mice cells. Afterwards, they are cultured in mediums treated with an anti-CD3 antibody.

At 24 hours, the cultures are centrifuged. The supernatants are then assayed for cytokine content.

For Animal Experiment

In the animal trial, the scholars target the mice-bearing SK-OV-3, U87MG, and HCT 116 xenograft models.

The drug is administered intraperitoneally through an injection. For SK-OV-3, the dosage is 10ml/kg taken once or twice daily for 21 and 16 days, respectively. For U87MG, the dose lasts for 14 days while for HCT 116; it’s seven days long.

5.What Is A66 Used For?

A66 clamps down on high levels of oncogenic p110α, which are responsible for certain cancerous tumors on specific cell types. As at now, the treatment copes with endometrial cancer.

Although A-66 does not trigger the regression of tumors in xenograft models, the biochemical is an efficient cytostatic agent in certain tumors. It induces growth delay in the HCT 116 cell lines of xenografted models. Clinicians can buy the biochemical and club it with other oncogene therapies to inhibit tumor growth in xenografts.

A66 upregulates glucose output while bringing insulin resistance to a halt.

6. How should you store A66?

The typical storage temperature of A66 is below -20°C. From the time you purchase 1166227-08-2, its shelf life will extend to almost three years. At 4°C, it will be usable for the next two years. As a solvent, it will remain valid for only a month. However, you can freeze it as far as -80°C if you want the A66 solution to last up to six months.

When ready to use, you can warm the product to room temperature or at 37°C. In doing so, you will obtain a higher solubility than when dissolving chilly A66 inhibitor.

Once you buy 1166227-08-2, keep it sealed up, away from air, direct light, potent oxidizing agents, and concentrated acids/bases. The location ought to have maximum ventilation and away from an ignition source. Note that extreme conditions may lead to decomposition.

During transportation, it is recommended that the A66 supplier ships the product at room temperature.

7. A66 Precautions

Although the product is non-hazardous, it is strictly for research purposes only. Before you can order 1166227-08-2 online, you should note that it is neither for therapeutic nor for veterinary use.

During combustion, it’s likely to give off irritant fumes. Therefore, it is suitable to wear protective clothing and desist from taking in any vapors or fumes during the experiment. Personal protection entails covering your eyes, skin, respiratory system, and the entire body.

If you accidentally ingest the chemical, cleanse your mouth with enough cold water. Upon inhalation, you’ll need to move to a well-ventilated area to freshen up. In the case of eye or skin contact, thoroughly wash the affected spot with plenty of water.

While there’s no data to bracket A66 together with environmental pollution, A66 suppliers insist that you contain any spillages. Make sure to look through the compound’s safety data sheet before experimenting with it. Do not allow the spills to flow into drainages or watercourses. Disposal should conform to the prevailing federal regulations.

In line with GHS classification, A66 inhibitor is not a hazardous compound. Its constituents do not exceed the occupational exposure limit. Besides, there’s no data to yoke this product with toxicological effects.

 

References

  1. Foukas, L.C., Bettedi, L., Bilanges, B., et al. (2013). Long-Term p110α P13K Inactivation Exerts a Beneficial Effects on Metabolism.
  2. Jamieson, S., Kendall, J.D., et al. (2011). A Drug Targeting only p110α can Block Phosphoinositide 3-Kinase Signaling and Tumor Growth in Certain Cell Types.
  3. Rao, T., Utermark, T., Wang, Q., et al. (2012). The p110α and p110β isoforms of P13K Play Divergent Roles in Mammary Gland Development and Tumorigenesis. Genes Dev.
  4. Sun, M., et al. (2010). Cancer-Derived Mutations in the Regulatory Subunit p85α of phosphoinositide 3-kinase function through the Catalytic Subunit p110α.
  5. Wang, X., Yang, Y., Li, J.P., Ding, J., and Meng, L.H. (2013) A pharmacological model reveals biased dependency on PI3K isoforms for tumor cell growth.