nimotuzumab nimotuzumab nimotuzumab (h-r3, biomab egfr, biocon, india; theracim, cimym biosciences, canada; theraloc, oncoscience, europe, cimaher, center of molecular immunology, havana, cuba) is a humanized monoclonal antibody that as of 2014 had orphan status in the us and eu for glioma, and marketing approval in india, china, and other countries for squamous cell carcinomas of the head and neck, and was undergoing several clinical trials. nimotuzumabmonoclonal antibodytypewhole antibodysourcehumanized (from mouse)targetegfrclinical dataroutes ofadministrationintravenousatc codel01xc pharmacokinetic dataelimination half-life62–304 hoursidentifierscas number780758-10-3 nchemspidernoneunii6ns400bxkhchemical and physical dataformulac6566h10082n1746o2056s40molar mass147659.45 g·mol−1 ny (what is this?) (verify) like cetuximab, nimotuzumab binds to the epidermal growth factor receptor (egfr), a signalling protein that normally controls cell division. in some cancers, this receptor is altered to cause uncontrolled cell division, a hallmark of cancer. these monoclonal antibodies block egfr and stop the uncontrolled cell division. it has a humanized human-mouse h-r3 heavy chain and a humanized human-mouse h-r3 κ-chain. mechanism nimotuzumab binds with optimal affinity and high specificity to the extracellular region of egfr (epidermal growth factor receptor). this results in a blockade of ligand binding and receptor activation. epidermal growth factor receptor (egfr) is a key target in the development of cancer therapeutics. egfr-targeting drugs have been shown to improve response when used with conventional treatments such as radiation therapy and chemotherapy. development status it was developed at the center of molecular immunology (cim) in havana, cuba. cim's commercialization arm, cimab s.a. formed a joint venture with ym biosciences called cimym biosciences in 1995 that was 80% owned by ym and 20% owned by cimab. cimym biosciences licensed european rights to nimotuzumab to oncoscience ag in 2003, the south korean rights to kuhnil pharmaceutical co., ltd. in 2005, and in 2006, licensed the japanese rights to daiichi sankyo and rights to certain countries in asia and africa to innogene kalbiotech pte ltd. other licensees for nimotuzumab include biocon biopharmaceuticals ltd. (bbpl) in india, biotech pharmaceutical co. ltd. in china, delta laboratories in colombia, european chemicals sac, quality pharma in peru, eurofarma laboratorios ltda. in brazil, ferozsons labs in pakistan, laboratorio elea s.a.c.i.f.ya. in argentina, el kendi pharmaceutical in algeria and laboratorios pisa in mexico. in december 2012, cimym biosciences dissolved and sold its assets related to nimotuzumab to innokeys pte ltd. according to a 2009 review: "nimotuzumab was approved for the following indications—for squamous cell carcinoma in head and neck (scchn) in india, cuba, argentina, colombia, ivory coast, gabon, ukraine, peru and sri lanka (expired now); for glioma (pediatric and adult) in cuba, argentina, philippines and ukraine; for nasopharyngeal cancer in china. it has been granted orphan drug status for glioma in usa and for glioma and pancreatic cancer in europe." as of 2014 nimotuzumab was in additional phase i and ii clinical trials. in april 2014, daiichi sankyo announced that it was halting a multicenter, randomized, double-blind, placebo-controlled phase iii study investigating nimotuzumab for first-line therapy in patients with unresectable and locally advanced squamous cell lung cancer, due to safety issues in certain patients who received a combination of cisplatin, vinorelbine, radiotherapy, and nimotuzumab. safety the toxicity and safety of nimotuzumab have been assessed in several pre-clinical and clinical studies wherein it was noticed that side effects usually caused by egfr inhibitors, especially rashes and other skin toxicities, were negligible. scientists have hypothesized that this is because nimotuzumab binds only to cells that express moderate to high egfr levels. nimotuzumab has been found to be very well tolerated in clinical trials. common adverse reactions seen in patients treated with nimotuzumab include: chills fever nausea and vomiting dryness of mouth asthenia hypertension/hypotension flushing notes who drug information, vol. 19, no. 4, 2005 proposed inn list 94, p.333 ramakrishnan ms, eswaraiah a, crombet t, piedra p, saurez g, iyer h, arvind as (2009). "nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin". mabs. 1 (1): 41–8. doi:10.4161/mabs.1.1.7509. pmc 2715181. pmid 20046573. biomab egfr (biocon, india) merck index 14th edition monograph number 10585. mateo c, moreno e, amour k, lombardero j, harris w, pérez r (march 1997). "humanization of a mouse monoclonal antibody that blocks the epidermal growth factor receptor: recovery of antagonistic activity". immunotechnology. 3 (1): 71–81. doi:10.1016/s1380-2933(97)00065-1. pmid 9154469. ym biosciences ym biosciences annual report for year ended june 30, 2007 archived september 7, 2017, at the wayback machine ym biosciences press release. december 2012 ym biosciences reports divestiture of nimotuzumab assets by cimym vacchelli e, aranda f, eggermont a, galon j, sautès-fridman c, zitvogel l, et al. (january 2014). "trial watch: tumor-targeting monoclonal antibodies in cancer therapy". oncoimmunology. 3 (1): e27048. doi:10.4161/onci.27048. pmc 3937194. pmid 24605265. daiichi sankyo press release. april 25, 2014 daiichi sankyo announces discontinuation of phase 3 clinical trial in japan of nimotuzumab (de-766) in lung cancer theracim official site biomab insert monoclonal antibodies for tumorstumorhuman adecatumumab§ amivantamab ascrinvacumab§ atezolizumab balstilimab† botensilimab cixutumumab§ conatumumab§ daratumumab drozitumab§ duligotumab§ dusigitumab§ enfortumab vedotin enoticumab§ figitumumab§ flanvotumab§ ganitumab† glembatumumab vedotin† intetumumab§ ipilimumab iratumumab§ istiratumab icrucumab§ lexatumumab§ lucatumumab§ mapatumumab§ narnatumab§ necitumumab nesvacumab§ nivolumab# ofatumumab olaratumab† panitumumab patritumab§ pembrolizumab# pritumumab§ radretumab§ ramucirumab rilotumumab† robatumumab§ seribantumab§ tarextumab§ tisotumab vedotin teprotumumab† tovetumab§ vantictumab§ votumumab§ zalutumumab† mouse abagovomab altumomab pentetate anatumomab mafenatox arcitumomab bectumomab blinatumomab capromab pendetide detumomab edrecolomab ibritumomab tiuxetan igovomab lilotomab minretumomab mitumomab nacolomab tafenatox moxetumomab pasudotox naptumomab estafenatox oregovomab pemtumomab† racotumomab satumomab pendetide solitomab taplitumomab paptox nofetumomab merpentan pintumomab tenatumomab tositumomab chimeric amatuximab§ bavituximab§ brentuximab vedotin carotuximab† cetuximab derlotuximab biotin§ dinutuximab ecromeximab§ ensituximab§ futuximab§ girentuximab† indatuximab ravtansine§ isatuximab loncastuximab tesirine margetuximab mirvetuximab soravtansine rituximab# siltuximab ublituximab humanized abituzumab§ alemtuzumab belantamab mafodotin bevacizumab bivatuzumab mertansine§ brontictuzumab§ cantuzumab mertansine§ cantuzumab ravtansine§ cirmtuzumab citatuzumab bogatox§ clivatuzumab tetraxetan cofetuzumab pelidotin dacetuzumab§ demcizumab§ dalotuzumab§ denintuzumab mafodotin§ elotuzumab emactuzumab emibetuzumab§ enoblituzumab§ etaracizumab§ farletuzumab§ ficlatuzumab§ flotetuzumab§ gemtuzumab ozogamicin glofitamab imgatuzumab§ inotuzumab ozogamicin labetuzumab§ lifastuzumab vedotin§ lintuzumab§ lorvotuzumab mertansine§ lumretuzumab§ matuzumab§ milatuzumab§ naxitamab nimotuzumab† obinutuzumab ocaratuzumab§ otlertuzumab§ onartuzumab§ oportuzumab monatox† parsatuzumab§ pertuzumab pinatuzumab vedotin§ polatuzumab vedotin rosmantuzumab rovalpituzumab tesirine† sacituzumab govitecan sibrotuzumab§ simtuzumab§ sofituzumab vedotin§ tacatuzumab tetraxetan§ tigatuzumab§ trastuzumab# (+deruxtecan / +emtansine) tucotuzumab celmoleukin§ vandortuzumab vedotin§ vanucizumab§ veltuzumab§ vorsetuzumab mafodotin§ pankomab rat/mouse hybrid catumaxomab ertumaxomab§ chimeric + humanized depatuxizumab mafodotin† duvortuxizumab ontuxizumab§ #who-em ‡withdrawn from market clinical trials: †phase iii §never to phase iii growth factor receptor modulatorsangiopoietin agonists: angiopoietin 1 angiopoietin 4 antagonists: angiopoietin 2 angiopoietin 3 kinase inhibitors: altiratinib ce-245677 rebastinib antibodies: evinacumab (against angiopoietin 3) nesvacumab (against angiopoietin 2) cntf agonists: axokine cntf dapiclermin egf (erbb)egf(erbb1/her1) agonists: amphiregulin betacellulin egf (urogastrone) epigen epiregulin heparin-binding egf-like growth factor (hb-egf) murodermin nepidermin transforming growth factor alpha (tgfα) kinase inhibitors: afatinib agerafenib brigatinib canertinib dacomitinib erlotinib gefitinib grandinin icotinib lapatinib neratinib osimertinib vandetanib whi-p 154 antibodies: cetuximab depatuxizumab depatuxizumab mafodotin futuximab imgatuzumab matuzumab necitumumab nimotuzumab panitumumab zalutumumab erbb2/her2 agonists: unknown/none antibodies: ertumaxomab pertuzumab trastuzumab trastuzumab deruxtecan trastuzumab duocarmazine trastuzumab emtansine kinase inhibitors: afatinib lapatinib mubritinib neratinib tucatinib erbb3/her3 agonists: neuregulins (heregulins) (1, 2, 6 (neuroglycan c)) antibodies: duligotumab patritumab seribantumab erbb4/her4 agonists: betacellulin epigen heparin-binding egf-like growth factor (hb-egf) neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, tmeff)) fgffgfr1 agonists: ersofermin fgf (1, 2 (bfgf), 3, 4, 5, 6, 8, 10 (kgf2), 20) repifermin selpercatinib trafermin velafermin fgfr2 agonists: ersofermin fgf (1, 2 (bfgf), 3, 4, 5, 6, 7 (kgf), 8, 9, 10 (kgf2), 17, 18, 22) palifermin repifermin selpercatinib sprifermin trafermin antibodies: aprutumab aprutumab ixadotin kinase inhibitors: infigratinib fgfr3 agonists: ersofermin fgf (1, 2 (bfgf), 4, 8, 9, 18, 23) selpercatinib sprifermin trafermin antibodies: burosumab (against fgf23) fgfr4 agonists: ersofermin fgf (1, 2 (bfgf), 4, 6, 8, 9, 19) trafermin unsorted agonists: fgf15/19 hgf (c-met) agonists: fosgonimeton hepatocyte growth factor potentiators: dihexa (pnb-0408) kinase inhibitors: altiratinib am7 amg-458 amuvatinib bms-777607 cabozantinib capmatinib crizotinib foretinib golvatinib incb28060 jnj-38877605 k252a mk-2461 pf-04217903 pf-2341066 pha-665752 su-11274 tivantinib volitinib antibodies: emibetuzumab ficlatuzumab flanvotumab onartuzumab rilotumumab telisotuzumab telisotuzumab vedotin igfigf-1 agonists: des(1-3)igf-1 insulin-like growth factor-1 (somatomedin c) igf-1 lr3 insulin-like growth factor-2 (somatomedin a) insulin mecasermin mecasermin rinfabate kinase inhibitors: bms-754807 linsitinib nvp-adw742 nvp-aew541 osl-906 antibodies: ave-1642 cixutumumab dalotuzumab figitumumab ganitumab robatumumab r1507 teprotumumab xentuzumab (against igf-1 and igf-2) igf-2 agonists: insulin-like growth factor-2 (somatomedin a) antibodies: dusigitumab xentuzumab (against igf-1 and igf-2) others binding proteins: igfbp (1, 2, 3, 4, 5, 6, 7) cleavage products/derivatives with unknown target: glypromate (gpe, (1-3)igf-1) trofinetide lngf (p75ntr) agonists: bdnf bnn-20 bnn-27 cenegermin dhea dhea-s ngf nt-3 nt-4 antagonists: ale-0540 dexamethasone evt-901 (sar-127963) testosterone antibodies: against ngf: abt-110 (pg110) asp-6294 fasinumab frunevetmab fulranumab medi-578 ranevetmab tanezumab aptamers: against ngf: rbm-004 decoy receptors: levi-04 (p75ntr-fc) pdgf agonists: becaplermin platelet-derived growth factor (a, b, c, d) kinase inhibitors: agerafenib avapritinib axitinib crenolanib imatinib lenvatinib masitinib motesanib nintedanib pazopanib radotinib quizartinib ripretinib sunitinib sorafenib toceranib antibodies: olaratumab ramucirumab tovetumab ret (gfl)gfrα1 agonists: glial cell line-derived neurotrophic factor (gdnf) liatermin kinase inhibitors: vandetanib gfrα2 agonists: neurturin (nrtn) kinase inhibitors: vandetanib gfrα3 agonists: artemin (artn) kinase inhibitors: vandetanib gfrα4 agonists: persephin (pspn) kinase inhibitors: vandetanib unsorted kinase inhibitors: agerafenib scf (c-kit) agonists: ancestim stem cell factor kinase inhibitors: agerafenib axitinib dasatinib imatinib masitinib nilotinib pazopanib quizartinib sorafenib sunitinib toceranib tgfβ see here instead. trktrka agonists: amitriptyline bnn-20 bnn-27 cenegermin dhea dhea-s gambogic amide ngf tavilermide antagonists: ale-0540 dexamethasone fx007 testosterone negative allosteric modulators: vm-902a kinase inhibitors: altiratinib azd-6918 ce-245677 ch-7057288 ds-6051 entrectinib gz-389988 k252a larotrectinib lestaurtinib milciclib ono-4474 ono-5390556 plx-7486 rebastinib sna-120 (pegylated k252a)) antibodies: against trka: gbr-900; against ngf: abt-110 (pg110) asp-6294 fasinumab frunevetmab fulranumab medi-578 ranevetmab tanezumab aptamers: against ngf: rbm-004 decoy receptors: ren-1820 (trkad5) trkb agonists: 3,7-dhf 3,7,8,2'-thf 4'-dma-7,8-dhf 7,3'-dhf 7,8-dhf 7,8,2'-thf 7,8,3'-thf amitriptyline bdnf bnn-20 deoxygedunin deprenyl diosmetin dmaq-b1 hioc lm22a-4 n-acetylserotonin nt-3 nt-4 norwogonin (5,7,8-thf) r7 r13 tdp6 antagonists: ana-12 cyclotraxin b gossypetin (3,5,7,8,3',4'-hhf) ligands: dhea kinase inhibitors: altiratinib azd-6918 ce-245677 ch-7057288 ds-6051 entrectinib gz-389988 k252a larotrectinib lestaurtinib ono-4474 ono-5390556 plx-7486 trkc agonists: bnn-20 dhea nt-3 kinase inhibitors: altiratinib azd-6918 ce-245677 ch-7057288 ds-6051 entrectinib gz-389988 k252a larotrectinib lestaurtinib ono-4474 ono-5390556 plx-7486 vegf agonists: placental growth factor (pgf) ripretinib telbermin vegf (a, b, c, d (figf)) allosteric modulators: cyclotraxin b kinase inhibitors: agerafenib altiratinib axitinib cabozantinib cediranib lapatinib lenvatinib motesanib nintedanib pazopanib pegaptanib rebastinib regorafenib semaxanib sorafenib sunitinib toceranib tivozanib vandetanib whi-p 154 antibodies: alacizumab pegol bevacizumab icrucumab ramucirumab ranibizumab decoy receptors: aflibercept others additional growth factors: adrenomedullin colony-stimulating factors (see here instead) connective tissue growth factor (ctgf) ephrins (a1, a2, a3, a4, a5, b1, b2, b3) erythropoietin (see here instead) glucose-6-phosphate isomerase (gpi; pgi, phi, amf) glia maturation factor (gmf) hepatoma-derived growth factor (hdgf) interleukins/t-cell growth factors (see here instead) leukemia inhibitory factor (lif) macrophage-stimulating protein (msp; hlp, hgflp) midkine (negf2) migration-stimulating factor (msf; prg4) oncomodulin pituitary adenylate cyclase-activating peptide (pacap) pleiotrophin renalase thrombopoietin (see here instead) wnt signaling proteins additional growth factor receptor modulators: cerebrolysin (neurotrophin mixture) this article is issued from wikipedia. the text is licensed under creative commons - attribution - sharealike. additional terms may apply for the media files.