Breast cancer is the most frequent cancer among women, impacting 2.1 million women each year, and also causes the greatest number of cancer-related deaths among women. In 2018, it is estimated that 627,000 women died from breast cancer – that is approximately 15% of all cancer deaths among women. While breast cancer rates are higher among women in more developed regions, rates are increasing in nearly every region globally.

The majority of patients with metastatic breast cancer (MBC) have hormone receptor-positive HER2-negative disease. For this subgroup, endocrine therapy is the key therapeutic option. Recently, therapeutic options have been expanded by the introduction of the inhibitors of cyclin-dependent kinases 4/6 (CDK4/6i). Three compounds, palbociclib, ribociclib, and abemaciclib, have already been approved by the FDA for use together with endocrine therapy such as aromatase inhibitors (AIs) or fulvestrant; abemaciclib is also approved as a single agent. Now, let’s make a comparison of CDK4/6 inhibitors.

1. Verzenio (Abemaciclib）

According to the approval time from near to far, let’s look at Verzenio first. Verzenio is a selective CDK4 and CDK6 inhibitor with IC50 values of 2 nM and 10 nM for CDK4 and CDK6 inhibitory activity, respectively.

The FDA granted Verzenio “breakthrough therapy” status in 2015, and then received Eli Lilly’s New Drug Application on May 5, 2017, followed by Verzenio priority review status on July 10, 2017. There are two approved Verzenio therapies. One is combined with fulvestrant to treat female patients with advanced HR-positive and HER2-negative advanced metastatic breast cancer who have deteriorated after receiving endocrine therapy; the other is used as a monotherapy to treat adult patients with advanced metastatic breast cancer who were exacerbated after endocrine therapy and who were HR positive and HER2 negative before chemotherapy. Compared with other drugs of the same type, its characteristic is that it can be used as a monotherapy.

Common side effects that Verzenio may cause include diarrhea, neutropenia, nausea, abdominal pain, infection, fatigue, decreased red blood cell levels (anemia), loss of appetite, vomiting, headache. Serious side effects include diarrhea, neutropenia, liver Examination of blood and coagulation (deep vein thrombosis / pulmonary embolism). In addition, Verzenio may cause harm to developing fetuses and is not suitable for pregnant women.

2. Kisqali (Ribociclib)

Kisqali is the second FDA-approved oral CDK4 / 6 inhibitor with IC50 values of 10 nM and 39 nM for CDK4 and CDK6 inhibitory activity, respectively.

On March 13, 2017, Kisqali, a targeted anticancer drug developed by Novartis, was approved by the FDA. The combination of Kisqali and aromatase inhibitors are the first-line treatment for women with HR-positive and HER2-negative postmenopausal advanced metastatic breast cancer. Kisqali has achieved breakthrough therapy and priority review certification before being approved.

Common side effects seen in patients include neutropenia, nausea, fatigue, diarrhea, leukopenia, hair loss, vomiting, constipation, headache and back pain.

3, Ibrance (Palbociclib)

Ibrance is an FDA-approved CDK4 / 6 inhibitor with IC50 values of 11 nM and 16 nM for CDK4 and CDK6 inhibitory activity, respectively.

Although Pfizer’s development of Ibrance has been bumpy. But finally, on February 3, 2015, the FDA accelerated the approval of Ibrance’s marketing application, which is used in combination with letrozole to treat postmenopausal metastatic breast cancer patients with estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Also prior to approval, Ibrance has achieved breakthrough therapy certification and priority review qualifications. Ibrance’s successful launch is a milestone in the development of CDK inhibitors.

Common side effects seen in patients include Nausea, vomiting, loss of appetite, diarrhea, tiredness, weakness, hair loss, mouth sores, or numbness/tingling of arms/legs.

Huateng Pharma, a professional manufacturer of pharmaceutical API and intermediates, provides Palbociclib and Ribociclib key intermediates with high purity.

Palbociclib Intermediates: CAS NO. 571189-16-7, CAS No. 571188-59-5
Ribociclib Intermediates: CAS No.: 733039-20-8, CAS No. 571188-59-5, CAS No. 52092-47-4