Apatinib

Last updated
Apatinib
Apatinib structure.svg
Clinical data
Other namesRivoceranib; YN968D1
Routes of
administration
Oral
ATC code
  • none
Identifiers
  • N-(4-(1-Cyanocyclopentyl)phenyl)-2-((pyridin-4-ylmethyl)amino)nicotinamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C24H23N5O
Molar mass 397.482 g·mol−1
3D model (JSmol)
  • N#CC1(c2ccc(NC(=O)c3cccnc3NCc3ccncc3)cc2)CCCC1
  • InChI=1S/C24H23N5O/c25-17-24(11-1-2-12-24)19-5-7-20(8-6-19)29-23(30)21-4-3-13-27-22(21)28-16-18-9-14-26-15-10-18/h3-10,13-15H,1-2,11-12,16H2,(H,27,28)(H,29,30) Yes check.svgY
  • Key:WPEWQEMJFLWMLV-UHFFFAOYSA-N Yes check.svgY
   (verify)

Apatinib, also known as rivoceranib, 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. [1]

Contents

Apatinib was first synthesized by Advenchen Laboratories in California, USA and licensed out global rights to HLB (Korea) in 2020 and is being developed by Jiangsu Hengrui Medicine (China), LSK BioPartners (US) and HLB Life Science (Korea). [2] It is an investigational cancer drug currently undergoing clinical trials as a potential targeted treatment for metastatic gastric carcinoma, metastatic breast cancer, adenoid cystic carcinoma, and advanced hepatocellular carcinoma.

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 dose 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. [3]

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. [4]

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). [5] Apatinib was approved by CFDA in December, 2014 for patients with late-stage gastric carcinoma in China. [6] A phase IV study on safety of Apatinib started in April, 2015. The study aims to recruit 2,000 patients. [7]

As of November, 2010, two additional Phase II clinical studies have been initiated for apatinib in metastatic triple-negative breast cancer patients and advanced hepatocellular carcinoma. [8]

On March 7, 2011, Bukwang announced that it filed an IND to the Korean FDA to begin Human clinical studies of apatinib in Phase II. [9]

In August 2018, Bukwang licensed out the commercial rights in Korea for rivoceranib to HLB Life Science [10]

Non-clinical studies

Some cancer cells have the ability to develop resistance to the cytotoxic effects of certain cancer drugs (called multidrug resistance). A study concluded that apatinib may be useful in circumventing cancer cells' multidrug resistance to certain conventional antineoplastic drugs. [11] 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.[ citation needed ]

Related Research Articles

This is a list of terms related to oncology. The original source for this list was the US National Cancer Institute's public domain Dictionary of Cancer Terms.

<span class="mw-page-title-main">Sunitinib</span> Cancer medication

Sunitinib, sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in January 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.

<span class="mw-page-title-main">Lapatinib</span> Cancer medication

Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).

<span class="mw-page-title-main">Semaxanib</span> Chemical compound

Semaxanib is a tyrosine-kinase inhibitor drug designed by SUGEN as a cancer therapeutic. It is an experimental stage drug, not licensed for use on human patients outside clinical trials. Semaxanib is a potent and selective synthetic inhibitor of the Flk-1/KDR vascular endothelial growth factor (VEGF) receptor tyrosine kinase. It targets the VEGF pathway, and both in vivo and in vitro studies have demonstrated antiangiogenic potential.

<span class="mw-page-title-main">Cediranib</span> Chemical compound

Cediranib is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases.

<span class="mw-page-title-main">Axitinib</span> Chemical compound

Axitinib, sold under the brand name Inlyta, is a small molecule tyrosine kinase inhibitor developed by Pfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models and has shown partial responses in clinical trials with renal cell carcinoma (RCC) and several other tumour types.

<span class="mw-page-title-main">Eribulin</span> Pharmaceutical drug

Eribulin, sold under the brand name Halaven among others, is an anti-cancer medication used to treat breast cancer and liposarcoma.

Tigatuzumab (CS-1008) is a monoclonal antibody for the treatment of cancer. As of October 2009, a clinical trial for the treatment of pancreatic cancer, Phase II trials for colorectal cancer, non-small cell lung cancer, and ovarian cancer have been completed.

<span class="mw-page-title-main">Hycanthone</span> Chemical compound

Hycanthone is the schistosomicide approved by the FDA in 1975. It is a metabolite of lucanthone. Hycanthone interferes with parasite nerve function, resulting in paralysis and death. This agent also intercalates into DNA and inhibits RNA synthesis in vitro and shows potential antineoplastic activity.

<span class="mw-page-title-main">Lenvatinib</span> Chemical compound

Lenvatinib, sold under the brand name Lenvima among others, is an anti-cancer medication for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases.

<span class="mw-page-title-main">Vemurafenib</span> Targeted cancer drug

Vemurafenib (INN), sold under the brand name Zelboraf, is a medication used for the treatment of late-stage melanoma. It is an inhibitor of the B-Raf enzyme and was developed by Plexxikon.

Angiokinase inhibitors are a new therapeutic target for the management of cancer. They inhibit tumour angiogenesis, one of the key processes leading to invasion and metastasis of solid tumours, by targeting receptor tyrosine kinases. Examples include nintedanib, afatinib and motesanib.

<span class="mw-page-title-main">Cabozantinib</span> Chemical compound

Cabozantinib, sold under the brand names Cometriq and Cabometyx among others, is an anti-cancer medication used to treat medullary thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma. It is a small-molecule tyrosine-kinase inhibitor (TKI) of c-Met (HGFR) and VEGFR2, and also inhibits AXL, RET, and FLT3. It was discovered and developed by Exelixis Inc.

<span class="mw-page-title-main">Wolfram Samlowski</span> Oncologist

Wolfram Samlowski is an American medical oncologist with Comprehensive Cancer Centers of Nevada (CCCN) and a member of the Research Developmental Therapeutics and Genitourinary Committees for US Oncology. His research interests include translational research and development of novel cancer immunotherapy agents, translational drug development as well as gene therapy. His clinical interests are in developing more effective treatments for advanced stages of melanoma and non-melanoma skin cancers, and renal cancer.

<span class="mw-page-title-main">Brivanib alaninate</span> Chemical compound

Brivanib alaninate (INN/USAN) also known as BMS-582664 is an investigational, anti-tumorigenic drug for oral administration. The drug is being developed by Bristol-Myers Squibb for the treatment of hepatocellular carcinoma or HCC, the most common type of liver cancer. Brivanib is no longer in active development.

<span class="mw-page-title-main">Nivolumab</span> Anticancer medication

Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.

<span class="mw-page-title-main">Linsitinib</span> Chemical compound

Linsitinib is an experimental drug candidate for the treatment of various types of cancer. It is an inhibitor of the insulin receptor and of the insulin-like growth factor 1 receptor (IGF-1R). This prevents tumor cell proliferation and induces tumor cell apoptosis.

<span class="mw-page-title-main">Sonidegib</span> Chemical compound

Sonidegib (INN), sold under the brand name Odomzo, is a medication used to treat cancer.

<span class="mw-page-title-main">RO4929097</span> Chemical compound

RO4929097 (RG-4733) is a gamma secretase inhibitor being studied as an anti-cancer drug. Targeting gamma secretase inhibits NOTCH signaling, which is upregulated in many forms of cancer. The drug was initially developed by Roche for the treatment of Alzheimer's disease, but current research focuses on cancer. Production was halted in 2010, but began again in 2014.

VEGFR-2 inhibitor, also known as kinase insert domain receptor(KDR) inhibitor, are tyrosine kinase receptor inhibitors that reduce angiogenesis or lymphangiogenesis, leading to anticancer activity. Generally they are small, synthesised molecules that bind competitively to the ATP-site of the tyrosine kinase domain. VEGFR-2 selective inhibitor can interrupt multiple signaling pathways involved in tumor, including proliferation, metastasis and angiogenesis.

References

  1. "Rivoceranib mesylate". National Cancer Institute. 2011-02-02. Retrieved 2023-06-24.
  2. "Apatinib Mesylate (YN968D1)". LSK BioPartners. Archived from the original on 2011-07-13.
  3. Jin L (17 October 2009). "Novel Vascular Endothelial Growth Factor Receptor Inhibitor YN968D1 (Apatinib) Against advanced Malignancies: Phase I/II Study".
  4. Li J, Zhao X, Chen L, Guo H, Lv F, Jia K, et al. (October 2010). "Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies". BMC Cancer. 10: 529. doi: 10.1186/1471-2407-10-529 . PMC   2984425 . PMID   20923544.
  5. Clinical trial number NCT00970138 for "A Randomized Phase 2/3 Study of Apatinib as Third Line Treatment in Patients with Metastatic Gastric Carcinoma" at ClinicalTrials.gov
  6. "中国晚期胃癌小分子靶向药物研究取得突破" [Breakthrough in research on small molecule targeted drugs for advanced gastric cancer in China]. news.sina.com.cn (in Chinese). Retrieved 2015-11-02.
  7. "口服小分子靶向药物阿帕替尼开启大样本临床试验 - 丁香园" [Oral small molecule targeted drug apatinib starts large-sample clinical trial - Lilac Garden]. oncol.dxy.cn (in Chinese). Retrieved 2015-11-02.
  8. "Apatinib Search Results". Clinical Trials.gov.
  9. "부광약품, 항암제 임상2상 신청" [Bukwang Pharmaceutical applies for phase 2 clinical trial for anticancer drug] (in Korean). 7 March 2011.
  10. "Bukwang Pharm hands over marketing right over gastric cancer drug to HLB". Pulse by Maeil Business News Korea.
  11. Mi YJ, Liang YJ, Huang HB, Zhao HY, Wu CP, Wang F, et al. (October 2010). "Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters". Cancer Research. 70 (20): 7981–7991. doi:10.1158/0008-5472.CAN-10-0111. PMC   2969180 . PMID   20876799.