
cyclopamine

stiroyidal aalkkaloyidukalude kudumbatthil ulppedunna swaabhaavikamaayi undaakunna raasavasthuvaan cyclopamine (11-deoxojervin). ithu koonn lillie (veratrum californicum) yill ninnu verthirichedutha oru terratojanaanu, ithu marakamaaya janana vaikalyangalkk kaaranamaakunnu. ithu bhroona masthishkathe rund lobukalaayi (holoprocensfaliyude angeyattatthe roopam) verthirikkunnathil ninnu thadayunnu, ithu orotta kanninte (cyclopia) vikasanathinu kaaranamaakunnu. 1957ll thangalude attin koottangal cycloptic aattinkunjungalkk janmam nalkiyathinu sesham yuu. ezz. kaarshika vakuppumayi bandhapetta idaho attin karshakar aadyam soochippichathupole eee raasavasthuvin eee phalatthinte peraanu nalkiyirikkunnath. athinusesham cholam lilliye kuttavaaliyaayi thirichariyaan oru pathittaandilere samayameduthu. vyathyastha mazhayude reethikal aadukale vyathyasthamayi meyikkaan kaaranamayennum ithu garbhinikal kazhikkunna dhaanyathinte alavu baadikkunnuvennum pinneedulla padanangal soochippichu. vikasana samayat soonik hedge hogg signalling paathaye visham thadassappeduthunnu, angane janana vaikalyangalkk kaaranamaakunnu.
kandethalum naamakaranavum.
1957ll, idaho chemmariyaad valarthal vidagdhar us agrikalchar departmentumaayi (yuu. ezz. dii. eiii) bandhapettu, avarude aadukal marakamaaya otakkannulla vaikalyamulla aattinkunjungalkk janmam nalki. praadeshika sasyajaalangal shekharikkukayum avaye elikalkku bhakshanam nalkukayum cheytha sesham, yuu. ezz. dii. eiii shaasthranjar cyclopia punarnirmikkaan paadupettu. oru pathittaandinte pareekshanatthinum thettukalkkum sesham, avar kaattupannangal kaanukayum daanyangal ozhivakkaan krishikkaarodu upadeshikkukayum cheythu. california koonn lillie ennum ariyappedunna "veratrum kaalifornikkatthil" ninnu verthirichedutha moonnu stiroyidal alcaloidukalil onnaayirunnu cyclopamine, ennaal akkaalat anjjaathamaayirunnu, ithinu aadukalude bhroonangalil athinte phalangalude peraayirunnu nalkiyirikkunnath. naalu pathittaandukalkk sesham professor philipp beechiyude neethrthwathilulla oru samgham soonik hedge hogg jeenine cyclopamine aayi bandhappedutthi. pareekshanangalkk sesham, soonik hedge hogg jeenine nishabdamaakki avar cyclopia punarnirmmichu. professor beachy avarude cycloptic phalangal naalu pathittaandukalkk munbu paraamarshicha cycloptic aadukalumaayi bandhippichu. 
uravidavum ghadanayum.
cyclopamininte jaivasamshleshanam collustrollil ninnaan aarambhikkunnath. oru steroid asthikoodathinu mattoru 6,6 nuu sameepam oru classic 6 anga valayamundu, thudarnnu anchu allengil "6-6-6-5". "veratrum" ll anchu tharam alcaloidukal adangiyirikkaan theerumaanichu, avayil oronninum oru saadhaarana collustroll mungaamiyundaayirunnu (1) solanidine alcaloidukal, (2) verasin alcaloidukal, (3) vertramine alcaloidukal, (4) jerwine alcaloidukal, (5) sevanine alcaloidukal. biosynthesisil, cyclopamine oru solanide (1) mungamiyund, athu collustrollil ninnaan nirmmichirikkunnathu. koonn lillie ("veratrum californium") yill ninnu aalkkaloyidukale verthirichedukkukayum bhroona aadukale parichayappedutthukayum cheytha prarambha padanangal ithu nirnnayichu. akkaalat, jarwain ithinakam ariyappedunna oru aalkkaloyidaayirunnu, ithu mattu rund alcaloidukalkkoppam dhaanya lilliyil ninnu verthirichedukkappettu anjjaathamaaya cyclopamine, veratramine; oronnum vyathyastha vishaamshangalullavayaan. pinneedu nadanna padanangal theliyikkunnathu, wolf-kishner kuravu moolam jarwain cyclopamainaayi tharamthaazhthappedukayum ithu anjjaatha samyukthathe thirichariyaan sahayikkukayum cheythu.
levis assid (piechu <2) upayogichu cyclopamine chikilsikkunnathu veratramine ulppaadanathilekku nayikkunnuvennum theliyikkapettu. wier eee avasthakal nalkunnu, athinaal kazhichathinushesham cheria alavil cyclopamine maathrame vayariloode kadannupokunnulloo. kazhikkunna cyclopamine oru cheria alavil maathrame aamaashayathiloode kadannupokunnulloovenkum pinneedu athu baadhikkappedaathe thudarunnu.
serotoninu samaanamaayi, serotramine kendra naadeevyavasthaye uthejippikkukayum pidichedukkalinu kaaranamaakukayum cheiyunnathinaal, athu vikasanathe baadhikkunnillenkilum, veratramine valare vishaamshamullathaan. veratramine uthppaadippikkunnathinu samvidaanam oru kaarban-ooksijan bondinte pilarppil shradha kendreekarikkunnu, ithu oru puthiya eratta bondinte roopeekaranathilekku nayikkunnu. avide ninnu, eee mothiram eathaandu sugandhamullathaanu. sugandhamullathaayi maranullah prerakashakthi thudarnnu oru elemination prathikaranatthe thallukayum moonnaamathe erattabandham srishtikkukayum chuvadeyulla chithratthil chithreekarichirikkunnathu sugandham srishtikkukayum cheiyunnu. 
samvidaanam.
soonik hedge hogg (eshh) paathaye thadassappeduthunnathiloodu cyclopamine bhroona vikasanathe badhikkunnu.
aarogyakaramaya vikasanathil, shhaa proteinukalkkulla shhaa jeane kodukal. eee proteinukalkku "patched" enna uparithala membran proteinumaayi uyarnna aduppamundu. bandhippikkumbol, shhaa proteinukal paachu cheyyappedunnathu thadayunnu. paachu thadassappettaal, "smoothend" ennu vilikkunna mattoru uparithala membran protein kooduthal kaaskedukale soochippichekkaam, athu vikasanathe badhikkunnu.
cyclopamine sugamamaayathinodu uyarnna aduppamundu-bandhippikkumbol, signal thadayunnu. shhaa patched thadayumenkilum, smoothand cyclopamininte saannidhyathil signal cheyyaan kazhiyilla, athinaal paatha thadassappedunnu.
bhroonashaasthram.
cyclopamine holoprocensfaliyude ettavum noothanamaaya roopathinu kaaranamaakunnu. ithu shhaa signalingine thadayunnathinaal, bhroona masthishkam inii lobukalaayi vibhajikkappedunnilla (alobar aayi maarunnu). angane, oru opttikkal track maathrame vikasikkoo, athinaal cycloptic (singular) kannu. koodaathe, eee rogam maarakamaan, nilavil ithinu chikilsayilla. 
 aarogyamulla thalachorinte pakuthiyum vibhajikkappedaathe valarukayum alobar thalachorumaayi saamyamullathayirikkukayum cheiyumennu oraalkk sangalppikkaan kazhiyum. cyclopamine vishabaadhayude kesukalilaanu ithu sambhavikkunnath. eee vaikalyam ellaayppozhum maarakamaan, ellaayppozhum maarakamallaatha holoprocensphaly kesukal kuravaanennathu sradhikkendathaanu. ennirunnaalum, bhroona cyclopamine vishabaadha ettavum theevravum athinaal maarakavumaya kesukalkku kaaranamaakunnu.
medical saadhyathakal.
basel sell carcinoma, meduloblastoma, rabdomiosarcoma, amithamaya shhaa pravartthanam, glioblastoma ennivayil ninnu saadhaaranayaayi undaakunna tumours, multiple mylomayude chikitsa ejantu ennee nilakalil cyclopamine nilavil anweshikkappedunnu. udaaharanathinu, epithelial kansarinekkurichulla padanangal theliyikkunnathu tumour koshangal shhaa ligand sravikkunnu, ithu stromal koshangalude aduthulla valarchaa gadakangalude ulppaadanathe soochippikkunnu, ithu angiogenesis, tumour sell vyaapanam, tumour sell athijeevanam ennivayilekku nayikkunnu.
ithu manassil vechukondu, kaansarinte samvidaanathe kuraykkunnathinulla oru maargamaayi cyclopamine sangalppikkaan kazhiyum. ennirunnaalum, mouse senographt modalukalile tumour valarchaye thadayunnuvennu cyclopamine theliyikkappettilettum, sareerabhaaram kuraykkal, nirjjaleekaranam, mouse modalukalile maranam ennivayulppede niravadhi paarshwafalangalkku kaaranamayathinaal ithu orikkalum chikitsa seshiyil athiyilla.
cyclopamininte rund functional analogukalkku fda amgeekaaram nalkiyittundu; 2012 ll wismodegib, 2015 ll sonidegib. koodaathe, kyaansar chikilsikkunnathinaayi amgeekaricha aadyathe shhaa pathway marunnaan wismodegib.
cyclopamine vismodegib valare saamyamullathayi kaanappedunnillenkilum, vismodegibinte vikasanam cyclopamininte eathu vashangalaan ithinu pravartthanam nalkunnathennu velippeduthukayum aaa phalangal upayogichu wismodegib undaakkukayum cheythu. udaaharanathinu, vismodegibile cherttha chlorin group cyclopamyninekkaal valare uyarnna layaneeyata nalkunnu-kuranja layaneeyata cyclopamine oru praayogika marunnakkunnathinulla thadassamaanu. vismodegibinte vikasanam ghadana pravartthana bandhangal (saar) velippeduthukayum rund saittukalile hydrajan bandhavum layikkunnathum marunninte falaprapthy baadhikkunnuvenn nirnnayikkukayum cheythu. prathyekamaayi paranjaal, rund hydrajan bondukalum vipareeta reethikalil pravartthikkunnu; oru saittil smoothend resepterile oru tyrosine avashishtam oru prottoon sweekarikkaan vaagdaanam cheiyunnu, athesamayam oru prathyeka arjinin avashishtam hydrajan boond sweekarthaavaayi pravartthikkunnu. sweekarikkunna group kooduthal phalapradamaanenkilum, randum ullathinaal sakthamaaya bandhanam undaakkunnu. 

