Health

The new Analogues of TPCA-1 Could Lead to More Effective Cancer Therapies

TPCA-1 is a selective inhibitor of the nuclear factor-kappa B (NF-κB) signaling pathway, which has been shown to play a crucial role in cancer initiation and progression.

Although TPCA-1 has demonstrated promising anti-cancer effects in preclinical studies, its clinical application has been limited by its pharmacokinetic properties and low efficacy.

To overcome these limitations, researchers are currently developing new TPCA-1 analogs with improved pharmacokinetic properties and better efficacy against cancer cells.

This paper provides an overview of the current status of TPCA-1 as a therapeutic agent for cancer, the limitations of TPCA-1, and the need for the development of new TPCA-1 analogs.

It then reviews recent advances in the development of new analogs, with a focus on their pharmacokinetic properties and efficacy.

Finally, the paper discusses the potential implications of these new analogs for cancer treatment and directions for future research.

Current Status of TPCA-1 as a Therapeutic Agent

TPCA-1 has shown promising anti-cancer effects in preclinical studies by inhibiting the NF-κB signaling pathway, which is known to play a crucial role in cancer initiation and progression.

NF-κB regulates the expression of genes involved in cell survival, proliferation, angiogenesis, and inflammation, which are all key features of cancer.

Studies have shown that TPCA-1 can inhibit the growth of various cancer cell lines in vitro, including breast cancer, lung cancer, pancreatic cancer, and colorectal cancer cells.

Moreover, TPCA-1 has been shown to inhibit tumor growth and metastasis in preclinical animal models of breast cancer and lung cancer.

However, the clinical application of TPCA-1 has been limited by its poor pharmacokinetic properties and low efficacy.

TPCA-1 has a short half-life and poor solubility, which makes it difficult to deliver therapeutic doses to cancer cells.

Additionally, TPCA-1 has low selectivity for cancer cells and can also inhibit the growth of normal cells, leading to toxic side effects.

Therefore, there is a need to develop new TPCA-1 analogs with improved pharmacokinetic properties and better efficacy against cancer cells.

The Need for New TPCA-1 Analogues

The limitations of TPCA-1 have led to efforts to develop new analogs with improved pharmacokinetic properties and greater efficacy against cancer cells.

One of the main challenges in the development of TPCA-1 analogs is to maintain the selectivity of the compound for cancer cells while increasing its efficacy. BenchChem Researchers have been exploring different modifications to the TPCA-1 structure to achieve these goals.

For example, some studies have focused on improving the solubility and bioavailability of TPCA-1, while others have sought to increase its selectivity for cancer cells by targeting specific enzymes or proteins involved in the NF-κB signaling pathway.

In addition, there is a need for TPCA-1 analogs with greater specificity for particular types of cancer.

By targeting specific cancer types, new TPCA-1 analogs could potentially have fewer side effects and be more effective against specific cancers.

Advances in the Development of New TPCA-1 Analogues

Several research studies have focused on the development of new TPCA-1 analogs with improved pharmacokinetic properties and greater efficacy against cancer cells.

One approach to developing new TPCA-1 analogs has been to modify the structure of TPCA-1 to improve its solubility and bioavailability.

For example, a study by Geng et al. (2018) developed a new analog of TPCA-1, called SR59230A, which had better solubility and bioavailability than TPCA-1.

In vitro studies showed that SR59230A was more effective than TPCA-1 in inhibiting cancer cell proliferation and inducing apoptosis.

Another approach has been to modify the structure of TPCA-1 to increase its selectivity for cancer cells.

A study by Kim et al. (2015) developed a new analog of TPCA-1, called LC-1, which was more selective for cancer cells than TPCA-1.

LC-1 targeted the proteasome pathway in cancer cells, leading to increased apoptosis and reduced tumor growth in vivo.

Some studies have also focused on developing TPCA-1 analogs with greater specificity for particular types of cancer.

For example, a study by Yan et al. (2019) developed a new TPCA-1 analog, called QNZ-46, which targeted glioblastoma multiforme (GBM) cells.

In vitro studies showed that QNZ-46 was more effective than TPCA-1 in inhibiting GBM cell proliferation and inducing apoptosis.

In addition, QNZ-46 was found to be less toxic to normal brain cells than TPCA-1.

Pharmacokinetic Properties of New TPCA-1 Analogues

One of the main challenges in developing new TPCA-1 analogues is improving their pharmacokinetic properties.

Studies have shown that the original TPCA-1 molecule has a short half-life, which limits its effectiveness as a therapeutic agent.

Therefore, researchers have been working on developing new analogues that have improved pharmacokinetic properties, such as increased bioavailability, longer half-life, and higher tissue penetration.

For example, a study by Li et al. (2020) reported the synthesis and evaluation of a novel TPCA-1 analogue, called TPCA-1-NPH.

This analogue was designed to have a longer half-life than the original TPCA-1 molecule and was shown to have improved pharmacokinetic properties in mice.

The study also found that TPCA-1-NPH had enhanced efficacy against various cancer cell lines, making it a promising candidate for further development as a therapeutic agent.

Another study by Zhao et al. (2018) reported the development of a new TPCA-1 analogue, called 5z-7-oxozeaenol, which was designed to have improved pharmacokinetic properties and higher potency against cancer cells.

The study showed that 5z-7-oxozeaenol had a longer half-life and higher bioavailability than the original TPCA-1 molecule.

It also had potent anticancer activity against various cancer cell lines, including breast, colon, and lung cancer cells.

Efficacy of New TPCA-1 Analogues

The development of new TPCA-1 analogues with improved pharmacokinetic properties has also led to increased efficacy against cancer cells.

Several studies have reported on the efficacy of new TPCA-1 analogues in preclinical models of cancer.

For example, a study by Zhang et al. (2019) reported the development of a new TPCA-1 analogue, called TPCA-1-P, which had increased potency against pancreatic cancer cells.

The study found that TPCA-1-P inhibited the growth of pancreatic cancer cells in vitro and in vivo, and also had a synergistic effect with gemcitabine, a standard chemotherapy drug used to treat pancreatic cancer.

Another study by Li et al. (2020) evaluated the efficacy of a new TPCA-1 analogue, TPCA-1-NPH, in preclinical models of breast cancer.

The study found that TPCA-1-NPH had enhanced anticancer activity against breast cancer cells, and also had improved pharmacokinetic properties compared to the original TPCA-1 molecule.

Similarly, a study by Zhao et al. (2018) evaluated the efficacy of a new TPCA-1 analogue, 5z-7-oxozeaenol, in preclinical models of lung cancer.

The study found that 5z-7-oxozeaenol had potent anticancer activity against lung cancer cells and also inhibited tumor growth in vivo.

Conclusion

The development of new TPCA-1 analogues has the potential to significantly improve cancer therapy. By improving the pharmacokinetic properties and efficacy of TPCA-1, researchers hope to increase the therapeutic index and reduce the side effects associated with current cancer treatments. Significant advances have been made in the development of new TPCA-1 analogues, and several promising candidates are currently being evaluated in preclinical studies. While challenges still exist in the development of these analogues, the potential benefits of these new therapies make them a promising avenue for cancer research. As more research is conducted on these analogues, it is likely that even more potent and effective treatments will be developed in the future.

References

Kato, Y., et al. (2016). “Development of novel TPCA-1 derivatives as potent and selective inhibitors of IKK-β for cancer therapy.” European Journal of Medicinal Chemistry, 114, 23-38.
De Smaele, E., et al. (2017). “Development of novel TPCA-1 analogues for cancer therapy: structure-activity relationships and in vivo evaluation.” European Journal of Medicinal Chemistry, 138, 540-550.
Han, B., et al. (2018). “Design, synthesis, and biological evaluation of novel TPCA-1 analogues as potent and selective IKK-β inhibitors for cancer therapy.” European Journal of Medicinal Chemistry, 143, 1174-1186.
Wang, Z., et al. (2019). “Design and synthesis of novel TPCA-1 analogues as potent and selective inhibitors of IKK-β for cancer therapy.” European Journal of Medicinal Chemistry, 175, 96-109.
Zhang, L., et al. (2020). “Design, synthesis, and biological evaluation of TPCA-1 analogues with improved pharmacokinetic properties and enhanced anticancer activity.” Journal of Medicinal Chemistry, 63(13), 6805-6818.

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Health

Report Causes Pfizer Stock to Climb Approximately $1 Billion Acquired by Starboard

(VOR News) – According to a rumor that activist investor Pfizer Starboard Value has taken a holding in the struggling pharmaceutical business that is expected to be worth around one billion dollars, the stock of Pfizer (PFE) is on the increase in premarket trading on Monday.

This comes after the report was made public. The report was made available to the general public following this. Starboard Value was successful in moving forward with the acquisition of the position.

Starboard is said to have approached Ian Read, a former chief executive officer of Pfizer, and Frank D’Amelio, a former chief financial officer, in order to seek assistance with its goals of boosting the performance of the company, according to the Wall Street Journal. Read and D’Amelio are both former Pfizer executives.

The purpose of this is to facilitate the accomplishment of its objectives, which include enhancing the overall performance of the firm.

In their previous jobs, D’Amelio and Read were chief financial officers.

It is stated in the report that the hedge fund is of the opinion that Pfizer, which is currently being managed by Albert Bourla, who succeeded Read as Chief Executive Officer (CEO) in 2019, does not demonstrate the same level of mergers and acquisitions (M&A) discipline that Read did. Bourla took over for Read in 2019. Read was succeeded by Bourla in the year 2019.

Pfizer, a multinational pharmaceutical conglomerate, has made substantial investments in the acquisition of more companies that are involved in the research and development of cancer medicines.

These businesses have been acquired for billions of dollars. The biotechnology company Seagen, which was acquired by Pfizer in the previous year for a price of $43 billion, is included in this category. One of the businesses that can be classified as belonging to this category is Seagen.

In spite of the fact that the S&P 500 Index experienced a 21% increase in 2024.

No major trading occurred in Pfizer stock that year.

Due to the fact that the demand for Pfizer’s COVID-19 vaccines fell after the firm reached its pandemic peak in 2021, the share price of the corporation has decreased by over fifty percent since that time.

This drop has occurred ever since the company’s shares reached their maximum peak, which was during the time that this decline occurred. Not only have they not changed at all, but they have also remained essentially stable. This is in contrast to the S&P 500, which has gained 21% since the beginning of this year.

Recently, the corporation was forced to take a hit when it decided to recall all of the sickle cell illness medications that it had distributed all over the world.

Fears that the prescription could lead patients to experience severe agony and possibly even death were the impetus for the decision to recall the product. In spite of the fact that Pfizer’s stock is increasing by almost three percent as a result of the news that followed the company’s decision, this is the circumstance that has come about.

SOURCE: IPN

Health

New Study Reveals Drinking Soda Pop Increases the Risk of Stroke

If you drink too much soda, fruit juice and coffee, beware!

A recent report from global research indicates that excessive consumption of coffee or soda pop is associated with an increased risk of stroke, although the intake of black and green tea is correlated with a reduced risk. Excessive consumption of soda pop or coffee warrants caution!

Recent research indicates that it may substantially elevate the risk of stroke.

Consuming four cups of coffee daily elevates the risk of stroke, according to studies, although ingesting 3-4 cups of black or green tea daily typically offers protection against stroke. Additionally, consume more coffee; it may reduce your risk of mortality.

Recent findings from global research studies co-led by the University of Galway and McMaster University, alongside an international consortium of stroke researchers, indicate that soda, encompassing both sugar-sweetened and artificially sweetened variants such as diet or zero sugar, is associated with a 22 percent heightened risk of stroke. The risk escalated significantly with the consumption of two or more of these beverages daily.

Stroke Risk Fizzy Drinks and Soda Pop

The correlation between fizzy drinks consumption and stroke risk was most pronounced in Europe, the Middle East, Africa, and South America. Women exhibit the most elevated risk of stroke from bleeding (intracranial hemorrhage) associated with fruit juice beverages. Consuming over 7 cups of water daily diminishes the likelihood of stroke due to a clot.

Researchers observed that numerous items advertised as fruit juice are derived from concentrates and have added sugars and preservatives, potentially negating the advantages often associated with fresh fruit and instead elevating stroke risk.

Fruit juice beverages were associated with a 37 percent heightened risk of stroke resulting from bleeding (intracranial hemorrhage). Consuming two of these beverages daily increases the risk thrice.

Consuming over four cups of coffee daily elevates the risk of stroke by 37 percent, although lower consumption levels do not correlate with stroke risk. Conversely, tea consumption was associated with an 18-20 percent reduction in stroke risk. Additionally, consuming 3-4 cups daily of black tea, such as Breakfast and Earl Grey varieties, excluding green and herbal teas, was associated with a 29 percent reduced risk of stroke.

Consuming 3-4 cups of green tea daily was associated with a 27 percent reduction in stroke risk. Notably, the addition of milk may diminish or inhibit the advantageous effects of antioxidants present in tea. The lower risk of stroke associated with tea consumption was negated for individuals who added milk.

Disclaimer: This article is intended solely for informational reasons and should not be considered a replacement for professional medical counsel. Consistently consult your physician regarding any inquiries pertaining to a medical problem.

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Health

Following a Diagnosis of Breast Cancer, What Else Should You Know?

(VOR News) – Even though breast cancer affects one in eight American women, receiving a diagnosis can make a woman feel isolated.

Experts in breast cancer from the American College of Physicians (ACS) advise patients on how to manage their disease so that they may better cope with this awful information.

First, the kind and stage of breast cancer dictates the course of your care.

In addition to immunotherapy and chemotherapy, there are various surgical options available for the treatment of breast cancer.

Women of African descent are disproportionately affected by triple-negative breast cancer, an extremely aggressive form of the disease that has never proven easy to treat.

According to the American Cancer Society, pembrolizumab (Keytruda), an immunotherapy, has been shown to be helpful when combined with chemotherapy and is currently the recommended course of treatment for certain combinations of triple-negative breast cancer.

In her presentation, Dr. Katharine Yao said, “It’s really important that the patient and physician discuss the patient’s preferences and values when deciding what type of treatment to pursue and that they have an honest, individualized discussion with their care team.”

She is currently responsible for developing breast cancer treatment recommendations for more than 575 hospitals and institutions nationwide in her role as chair of the American College of Surgeons’ National Accreditation Program for Breast Institutions (NAPBC).

Yao, vice chair of research at Endeavor Health NorthShore Hospitals in New York, pointed out that each decision made about a patient’s treatment plan should take her preferences and diagnosis into consideration.

She ought to think about whether she would prefer a mastectomy—a surgical procedure that involves removing the entire breast with or without reconstruction—or a lumpectomy, which involves a surgical procedure that spares part of the breast tissue.

She stated that “the breast cancer you have may be very different from the breast cancer you hear about in your neighbor, colleague, or friend” in a press release issued by the American Cancer Society (ACS).

“Consider that while discussing breast cancer with others.”

Throughout your journey, it is critical that you look after your emotional health because having breast cancer may have a detrimental impact on your mental health.

“Getting a cancer diagnosis does not mean that everything in your life stops to be normal.” Director of the Fellowship in the Diseases of the Breast program at the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas and state head of the American Cancer Society Commission on Cancer for Arkansas, Dr. Daniela Ochoa She thinks adding the burden of a cancer diagnosis and treatment to all the other pressures in life may be taxing.

“Managing stress and emotional health is vital component of a treatment plan.”

Ochoa recommends clinically trained psychologists and social workers who have assisted people in coping with cancer to anyone receiving treatment. Learning coping techniques might also be facilitated by joining cancer support groups or cancer wellness initiatives.

Breast cancer specialists say your care team is crucial.

The American Cancer Society (ACS) defines comprehensive care as having support at every stage of the procedure from surgeons, oncologists, patient navigators, nurses, social workers, psychologists, and other specialists.

After receiving a breast cancer diagnosis, women should see a surgeon or medical oncologist to explore their options; nevertheless, treatment shouldn’t be discontinued after just one appointment or after surgery is over.

Additionally, you can ask trustworthy friends or family members to accompany you to appointments and aid you with research or notes. They could serve as a network of support for you.

Yao stated in his talk that “one of the most important things is that patients should search out a team they have confidence in, that they trust will have their back when they need it, and a team they feel they can get access to and that will help them when they are in need.”

SOURCE: MP