{{Short description|Chemical compound}} {{distinguish|afatinib|lapatinib}} {{Use dmy dates|date=March 2025}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | image = Apatinib structure.svg | image_class = skin-invert-image | width = 200 | alt = | caption =
<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | DailyMedID = <!-- DailyMed may use generic or brand name (generic name preferred) --> | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = Oral | class = | ATC_prefix = L01 | ATC_suffix = EK05 | ATC_supplemental =
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<!-- Identifiers --> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 811803-05-1 | PubChem = 11315474 | PubChem2 = 45139106 | IUPHAR_ligand = | DrugBank = DB14765 | ChemSpiderID = 9490441 | UNII = 5S371K6132 | KEGG = | ChEBI = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = | synonyms = Apatinib; YN968D1
<!-- Chemical and physical data --> | IUPAC_name = ''N''-(4-(1-Cyanocyclopentyl)phenyl)-2-((pyridin-4-ylmethyl)amino)nicotinamide | C = 24 | H = 23 | N = 5 | O =1 | SMILES = N#CC1(c2ccc(NC(=O)c3cccnc3NCc3ccncc3)cc2)CCCC1 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = WPEWQEMJFLWMLV-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}
'''Rivoceranib''', also known as '''apatinib''', 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, rivoceranib 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.<ref>{{Cite web |date=2011-02-02 |title=Rivoceranib mesylate |url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/rivoceranib-mesylate |access-date=2023-06-24 |website=National Cancer Institute |language=en}}</ref>
Apatinib was first synthesized by Advenchen Laboratories in California, US 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).<ref>{{cite web|url=http://www.lskbiopartners.com/new_site2008/sub03_01.htm |title=Apatinib Mesylate (YN968D1) |url-status=dead |archive-url=https://web.archive.org/web/20110713235112/http://www.lskbiopartners.com/new_site2008/sub03_01.htm |archive-date=2011-07-13 | work = LSK BioPartners }}</ref> It is an investigational cancer drug 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.<ref>{{cite web | vauthors = Jin L | date = 17 October 2009 |url=http://meeting.dxy.cn/2009CSCO/article/i9623-p1.html |title=Novel Vascular Endothelial Growth Factor Receptor Inhibitor YN968D1 (Apatinib） Against advanced Malignancies: phase I/II Study }}</ref>
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.<ref>{{cite journal | vauthors = Li J, Zhao X, Chen L, Guo H, Lv F, Jia K, Yv K, Wang F, Li C, Qian J, Zheng C, Zuo Y | display-authors = 6 | title = Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies | journal = BMC Cancer | volume = 10 | article-number = 529 | date = October 2010 | pmid = 20923544 | pmc = 2984425 | doi = 10.1186/1471-2407-10-529 | doi-access = free }}</ref>
==Status== {{outdated section|date=February 2018}} 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).<ref>{{ClinicalTrialsGov|NCT00970138|A Randomized Phase 2/3 Study of Apatinib as Third Line Treatment in Patients with Metastatic Gastric Carcinoma}}</ref> Apatinib was approved by CFDA in December, 2014 for patients with late-stage gastric carcinoma in China.<ref>{{Cite web|title = 中国晚期胃癌小分子靶向药物研究取得突破 | trans-title = Breakthrough in research on small molecule targeted drugs for advanced gastric cancer in China | language = Chinese |url = http://news.sina.com.cn/c/2014-12-13/194031282048.shtml|website = news.sina.com.cn|access-date = 2015-11-02}}</ref> A phase IV study on safety of Apatinib started in April, 2015. The study aims to recruit 2,000 patients.<ref>{{Cite web|title = 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 | trans-title = Oral small molecule targeted drug apatinib starts large-sample clinical trial - Lilac Garden | language = Chinese |url = http://oncol.dxy.cn/article/104656|website = oncol.dxy.cn|access-date = 2015-11-02}}</ref>
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.<ref>{{cite web | url = http://clinicaltrials.gov/ct2/results?term=apatinib | title =Apatinib Search Results | work = Clinical Trials.gov }}</ref>
In March 2011, Bukwang announced that it filed an IND to the Korean FDA to begin Human clinical studies of apatinib in phase II.<ref>{{Cite web|url=http://news.mk.co.kr/newsRead.php?year=2011&no=144122|title = 부광약품, 항암제 임상2상 신청 | trans-title = Bukwang Pharmaceutical applies for phase 2 clinical trial for anticancer drug | language = Korean |date = 7 March 2011}}</ref>
In August 2018, Bukwang licensed out the commercial rights in Korea for rivoceranib to HLB Life Science Medicare.<ref>{{Cite web|url=https://pulsenews.co.kr/view.php?year=2018&no=514387|title = Bukwang Pharm hands over marketing right over gastric cancer drug to HLB | work = Pulse by Maeil Business News Korea}}</ref>
==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.<ref>{{cite journal | vauthors = Mi YJ, Liang YJ, Huang HB, Zhao HY, Wu CP, Wang F, Tao LY, Zhang CZ, Dai CL, Tiwari AK, Ma XX, To KK, Ambudkar SV, Chen ZS, Fu LW | display-authors = 6 | title = Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters | journal = Cancer Research | volume = 70 | issue = 20 | pages = 7981–7991 | date = October 2010 | pmid = 20876799 | pmc = 2969180 | doi = 10.1158/0008-5472.CAN-10-0111 }}</ref> 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.{{cn|date=February 2023}}
== Society and culture == === Names === Rivoceranib is the international nonproprietary name<ref>{{cite journal | vauthors = ((World Health Organization)) | year = 2018 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79 | journal = WHO Drug Information | volume = 32 | issue = 1 | hdl = 10665/330941 | hdl-access = free | author-link = World Health Organization }}</ref> and the United States Adopted Name.<ref>{{cite web | title=Rivoceranib | website=AMA Finder | url=https://searchusan.ama-assn.org/finder/usan/search/FG-23/relevant/1/ | access-date=8 March 2025}}</ref>
== References == {{reflist}}
{{Extracellular chemotherapeutic agents}} {{Portal bar | Medicine}} {{Authority control}}
Category:Tyrosine kinase inhibitors Category:Experimental cancer drugs Category:Cyclopentanes Category:Drugs developed by Jiangsu Hengrui Category:2-Aminopyridines Category:4-Pyridyl compounds