Apatinib
Encyclopedia
Apatinib, also known as YN968D1, is a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR2, also known as KDR). It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis
in cancer cells; specifically apatinib inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel formation in tumor tissue. This agent also mildly inhibits c-Kit and c-SRC tyrosine kinases.
Apatinib was first synthesized by Advenchen Laboratories in California, USA and is being developed by Jiangsu Hengrui Medicine (China), LSK BioPartners (US) and Bukwang Pharmaceutical Company (Korea). It is an investigational cancer drug currently undergoing clinical trial
s as a potential targeted treatment
for metastatic gastric carcinoma, metastatic breast cancer
and advanced hepatocellular carcinoma
.
is determined to be 850 mg/day. The investigator also reported of 65 cancer patients treated in Phase I/II, 1.54% had a complete response, 12.31% had a partial response, 66.15% had stable disease and 20% had progressive disease.
A separate published report on the safety and pharmacokinetics of apatinib in Human clinical studies concludes that it has encouraging antitumor activity across a broad range of cancer types.
As of November, 2010, two additional Phase 2 clinical studies have been initiated for apatinib in metastatic triple-negative breast cancer patients and advanced hepatocellular carcinoma
.
On March 7, 2011, Bukwang announced that it filed an IND to the Korean FDA to begin Human clinical studies of Apatinib in Phase 2.
). A study concluded that apatinib may be useful in circumventing cancer cells' multidrug resistance to certain conventional antineoplastic drugs. The study showed that apatinib reverses the ABCB1- and ABCG2
-mediated multidrug resistance by inhibiting those functions and increasing the intracellular concentrations of the antineoplastic drugs. This study suggests that apatinib will be potentially effective in combination therapies with conventional anticancer drugs especially in cases where resistance to chemotherapy exists.
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
in cancer cells; specifically apatinib inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel formation in tumor tissue. This agent also mildly inhibits c-Kit and c-SRC tyrosine kinases.
Apatinib was first synthesized by Advenchen Laboratories in California, USA and is being developed by Jiangsu Hengrui Medicine (China), LSK BioPartners (US) and Bukwang Pharmaceutical Company (Korea). It is an investigational cancer drug currently undergoing clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s as a potential targeted treatment
Targeted therapy
Targeted therapy is a type of medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with rapidly dividing cells...
for metastatic gastric carcinoma, metastatic breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
and advanced hepatocellular carcinoma
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
.
Phase I/II clinical study
The principal investigator from Fudan University, China, presented results of Phase I/II human clinical studies at the 2009 CSCO Meeting (October 17, 2009). Cancer patients were administered varied doses of Apatinib daily for 28 days. Apatinib was well tolerated at doses below 750 mg/day, 3 of 3 dose limiting toxicities were reported at 1000 mg/day and the maximum tolerated doseMaximum tolerated dose
Maximum tolerated dose refers to the highest dose of a radiological or pharmacological treatment that will produce the desired effect without unacceptable toxicity...
is determined to be 850 mg/day. The investigator also reported of 65 cancer patients treated in Phase I/II, 1.54% had a complete response, 12.31% had a partial response, 66.15% had stable disease and 20% had progressive disease.
A separate published report on the safety and pharmacokinetics of apatinib in Human clinical studies concludes that it has encouraging antitumor activity across a broad range of cancer types.
Current status
There is a Phase II/III study recruiting patients in China to determine whether apatinib can improve progression free survival compared with placebo in patients with metastatic gastric carcinoma who have failed two lines of chemotherapy (September, 2009).As of November, 2010, two additional Phase 2 clinical studies have been initiated for apatinib in metastatic triple-negative breast cancer patients and advanced hepatocellular carcinoma
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
.
On March 7, 2011, Bukwang announced that it filed an IND to the Korean FDA to begin Human clinical studies of Apatinib in Phase 2.
Non-clinical studies
Some cancer cells have the ability to develop resistance to the cytotoxic effects of certain cancer drugs (called multidrug resistanceMultidrug resistance
Multiple drug resistance or Multidrug resistance is a condition enabling a disease-causing organism to resist distinct drugs or chemicals of a wide variety of structure and function targeted at eradicating the organism...
). A study concluded that apatinib may be useful in circumventing cancer cells' multidrug resistance to certain conventional antineoplastic drugs. The study showed that apatinib reverses the ABCB1- and ABCG2
ABCG2
ATP-binding cassette sub-family G member 2 is a protein that in humans is encoded by the ABCG2 gene. ABCG2 has also been designated as CDw338 . - External links :...
-mediated multidrug resistance by inhibiting those functions and increasing the intracellular concentrations of the antineoplastic drugs. This study suggests that apatinib will be potentially effective in combination therapies with conventional anticancer drugs especially in cases where resistance to chemotherapy exists.