#xpo1

[rnomics]

Global loss of cellular m6A #RNA methylation following infection with different SARS-CoV-2 variants [RESEARCH]

Insights into host–virus interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N6-Methyladenosine modification (m6A), one of the most abundant cellular #RNA modifications, regulates key processes in #RNA metabolism during stress response. Gene expression profiles observed postinfection with different SARS-CoV-2 variants show changes in the expression of genes related to #RNA catabolism, including m6A readers and erasers. We found that infection with SARS-CoV-2 variants causes a loss of m6A in cellular #RNAs, whereas m6A is detected abundantly in viral #RNA. METTL3, the m6A methyltransferase, shows an unusual cytoplasmic localization postinfection. The B.1.351 variant has a less-pronounced effect on METTL3 localization and loss of m6A than did the B.1 and B.1.1.7 variants. We also observed a loss of m6A upon SARS-CoV-2 infection in air/liquid interface cultures of human airway epithelia, confirming that m6A loss is characteristic of SARS-CoV-2-infected cells. Further, transcripts with m6A modification are preferentially down-regulated postinfection. Inhibition of the export protein XPO1 results in the restoration of METTL3 localization, recovery of m6A on cellular #RNA, and increased #mRNA expression. Stress granule formation, which is compromised by SARS-CoV-2 infection, is restored by XPO1 inhibition and accompanied by a reduced viral infection in vitro. Together, our study elucidates how SARS-CoV-2 inhibits the stress response and perturbs cellular gene expression in an m6A-dependent manner. http://genome.cshlp.org/cgi/content/short/33/3/299?rss=1&utm_source=dlvr.it&utm_medium=tumblr

[papersearch09]

Directing-Group-Based Method Which allows Intermolecular Heck-Type Reaction of Sorafenibketone Oxime Esters along with Unactivated Alkenes

MicroRNAs (miRNAs) are small non-coding RNAs that have been recognized to regulate the particular phrase associated with uncountable variety of genes. Their aberrant term has been seen as to be for this pathology of countless ailments including most cancers. You will find there's drive to develop miRNA focused therapeutics for several diseases especially cancer. Nonetheless, reining in these quick non-coding RNAs just isn't as easy since initially believed. This really is in view of the recent findings in which miRNAs they are under epigenetic laws in numerous quantities. Exportin Five health proteins (XPO5) atomic upload mediated regulation of miRNAs is one such crucial epigenetic system. XPO5 is in charge of transferring precursor miRNAs through the nuclear membrane layer to the cytoplasm, and is therefore a critical step in miRNA biogenesis. Many studies show in which variants within the different parts of the particular miRNA biogenesis paths, specially the aberrant term involving XPO5, raise the probability of establishing cancers. As well as XPO5, the actual Exportin 1 #Link# protein (XPO1) or even chromosome location servicing 1 (CRM1) can also hold miRNA export operate. These findings are usually backed up by path examines that disclose particular miRNAs since direct connection spouses regarding CRM1. An intensive comprehension of miRNA move mediated regulatory systems is very important for that effective kind of scientifically practical therapeutics. In this assessment, many of us identify the present understanding around the components associated with miRNA atomic transportation mediated regulation along with propose ways of uniquely block this particular crucial system within cancer malignancy.The first enantioselective total functionality of 10-isocyano-4-cadinene, a sea sesquiterpene singled out coming from nudibranchs in the family members Phyllidiidae, ended up being accomplished. Your cadinene is anticipated to become fresh nontoxic antifouling broker. Within the functionality, the intermolecular Diels-Alder response plus a SMl(Two)-induced Barbier-type reaction had been applied because essential #Link# measures. The absolute settings associated with 10-isocyano-4-cadinene was resolute to become (1S, 6S, 7R, 10S) on the basis of the complete activity. Antifouling pursuits in opposition to Balanus amphitrite with both enantiomers regarding 10-isocyano-4-cadinene ended up also looked at.Fresh crammed melon liquid has been subjected to thermosonication remedies along with processing factors involving temp (25-45 certifications Chemical), plethora stage (All day and.1-60 mu m) and also processing period (2-10 min) at the continuous frequency involving 30 kHz as well as pulse trips of 5 utes about and also 5 ersus away. Hunter coloration ideals (L*, a* along with 6*). lycopene (LC), phenolic content material (TP) along with vit c (Alcoholics anonymous) written content were tested. Greater retention associated with Alcoholics anonymous along with LC was witnessed from #Link# minimal treatment conditions. Alcoholics anonymous, LC & TP reduced significantly in larger amplitude amounts and at the maximum processing moment. A second get response function since the array of trial and error problems looked at was obtained for each with the compounds assessed. Style forecasts with regard to shade variables and bioactive ingredients have been closely linked to the fresh benefits acquired.

#Sorafenib #Temozolomide #Caramboxin

[denischerim]

. . . #esFujifilmX #fujifilm_xseries #fujixt2 #xpo1 #eyeshotmag #streetscenemag #streetshotmag #somewheremag #noicemag https://www.instagram.com/p/Ccbf7UmoCly/?igshid=NGJjMDIxMWI=

#esfujifilmx #fujifilm_xseries #fujixt2 #xpo1 #eyeshotmag #streetscenemag #streetshotmag #somewheremag #noicemag

[jorgeiboy23]

No existen palabras que expresen lo bonita que es nuestra amistad @natiss.98 🖤, que se combina con hermandad y momentos felices que durante estos años hemos compartido y que sin duda se transforman en buenos instantes de vida que estoy seguro llevamos en el corazón. ♥️ Agradecerte por estar en todos momentos, en los buenos y que importante estar también en los malos. 💛 Desde mi corazón gracias por tantos risas, comidas, molestaderas y por supuesto apoyo en mis sueños siempre. Te quiero muchísimo. ♥️ . . . . . . #quepeladoguate #perhapsyouneedalittleguatemala #instaguate #guatemala #portraitgt #devonartph #phicsion #urbaneandoguate #guatemalaimpresionante #igersgt #portraitlove #xpo1 #coquemiraesto #ownexvision (en Guatemala City, Guatemala) https://www.instagram.com/p/CQe9QEALyr5/?utm_medium=tumblr

#quepeladoguate #perhapsyouneedalittleguatemala #instaguate #guatemala #portraitgt #devonartph #phicsion #urbaneandoguate #guatemalaimpresionante #igersgt #portraitlove #xpo1 #coquemiraesto #ownexvision

[soulkurtk]

_ friends since 1990 _ 바람부는 날엔 압구정동을 가시고 바람부는 동네는 샌프란시스코 (ft. 어느덧 3년전 사진 속 병철리 + 멋진 사진 찍어준 지요) • • • • #샌프란시스코 #친구 #우정 #여행 #휴가 #추억 #스냅 #후지필름 #fujifilm #xpo1 #throwback #daily #vibe #vacay #sanfrancisco #sf #california #friends (at San Francisco, California)

#우정 #추억 #vibe #여행 #xpo1 #sf #throwback #friends #후지필름 #fujifilm #스냅 #daily #sanfrancisco #친구 #휴가 #california #샌프란시스코 #vacay

[eretzyisrael]

Cancer is a devious adversary. It figures out all kinds of ways to hide from the body’s detection systems and grow unchecked until it’s too late to stop them.

One of cancer’s most cunning methods of evading the immune system is to increase the frequency of a kind of cellular “train” – a protein called XPO1 – that makes regular back-and-forth trips in and out of the nucleus of a cell. The XPO1 protein’s job is to shuttle other proteins to the right stops on the line.

Read More: Israel21c

#karyopharm #Israel #myeloma #cancer

[ptmasterguide]

Selinexor (Mechanism of Action)

Selinexor (Mechanism of Action)

In this article, we will discuss Selinexor (Mechanism of Action). So, let’s get started. Mechanism of ActionIn nonclinical studies, selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus, reductions in several…

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#Anticancer Drugs #Medicine #Oncology #Pharmacology #Physiotherapy #Selinexor

[pharmaphorumuk]

Menarini bags blood cancer drug with $677M Stemline acquisition

Italian drugmaker Menarini has agreed to buy Stemline Therapeutics, bolting on an already-approved drug for a rare form of haematological cancer and establishing a beachhead in the US.

Privately-held Menarini is paying up to $677 million for Stemline and Elzonris (tagraxofusp-erzs), the biotech’s treatment for blastic plasmacytoid dendritic cell neoplasm (BPDCN), which was approved in the US towards the end of 2018.

Elzonris is the first drug to be specifically approved by the US regulator for BPDCN, an aggressive and rare disease of the bone marrow and blood that can affect multiple organs, including the lymph nodes and the skin, and can develop into a form of leukaemia.

Menarini is paying $12.50 per share for Stemline, a sizeable premium on the company’s share price of $4.75 before news of the deal emerged. A dollar of that total is in the form of a contingent value right (CVR) tied to the first sale of Elzonris in one of the top five EU markets.

The deal is the first major acquisition under Menarini’s group chief executive Elçin Barker Ergun, who took the helm of the family-owned drugmaker last year, moving from a role as head of new business at the healthcare division of Merck KGaA. It also shows that M&A can still continue despite the coronavirus pandemic.

Elzonris is a fusion protein consisting of interleukin-3 fused to diphtheria toxin that targets CD123, and in clinical trials achieved a complete response rate of 54% in adults and children aged over two with BPDCN. It is the first anti-CD123 drug to be approved anywhere in the world.

The drug has also been submitted for approval in the EU, with a decision from the EMA expected in the latter half of this year.

Menarini said it will use its presence outside the US to expand sales of Elzonris, which made just over $43 million in sales from the US market alone last year, with around $12 million of that coming from the fourth quarter.

That’s hardly breakneck sales growth, but BPDCN is a tiny market and Stemline has said diagnosis rates have been “choppy”.

The biotech has ambitions however to expand the use of the drug to other diseases that involve CD123, which include chronic myelomonocytic leukaemia (CMML), myelofibrosis and acute myeloid leukaemia (AML) – much larger opportunities.

One factor that may be holding back growth is a black box warning on Elzonris’ label in the US that it can cause capillary leak syndrome, which can sometimes be life-threatening.

The Stemline deal isn’t only about Elzonris, as the biotech also has an XPO1 inhibitor called SL-801 in phase I trials for advanced solid tumours and a RET inhibitor – SL-1001 – that is due to start clinical trials next year but is several years behind rival drugs from Eli Lilly and Blueprint Medicines.

The biotech ended the fourth quarter with $164 million in cash, thanks to a $76 million public offering that completed last summer.

Menarini licensed an AML candidate from Helsinn – HDAC inhibitor pracinostat – in late 2018, and also strengthened its position in antibiotics last year by acquiring rights to meropenem/vaborbactam, oritavancin and intravenous minocycline from Melinta Therapeutics in Europe.

“Stemline is an excellent fit for Menarini, enabling us to expand our presence in the US with an established biopharmaceutical company focused on developing oncology therapeutics,” said Barker Ergun.

“Through this acquisition, we will continue to strengthen our portfolio and pipeline of oncology assets and deliver novel therapies around the world,” she added.

The post Menarini bags blood cancer drug with $677M Stemline acquisition appeared first on .

from https://pharmaphorum.com/news/menarini-bags-blood-cancer-drug-with-677m-stemline-acquisition/

[miguelyantuche]

🌞 - - - - - - - - #sunset #sky #guatemala (en XPO1) https://www.instagram.com/p/B7CbIp3hYGo/?igshid=1qoxgbxtf0155

#sunset #sky #guatemala

[gozealouscloudcollection]

FDA批准了一種有風險的新型抗癌藥物 同時也發出警告

Selinexor與其他抗癌藥物的作用機製完全不同。這種藥物被稱為選擇性核輸出抑製劑，進入細胞並靶向將分子移入和移出細胞的機制。這個想法是癌細胞需要擺脫某種叫做XPO1的蛋白質來抑制腫瘤的生長，所以阻止這個過程會使它們更容易被破壞。

該藥最近通過了II期臨床試驗，結果顯示，其成功幫助25％被診斷患有多發性骨髓瘤的患者。在那些測試中，患者每週兩次接受80毫克selinexor和20毫克藥丸形式的地塞米松。這些患者已經接受了其他幾種癌症治療，但均沒有成功。其有效性的關鍵似乎在於它使用與其他治療不同的機制。

在考慮該試驗的數據後，FDA批准了selinexor用於多發性骨髓瘤患者的進一步檢測，但條件是他們已經嘗試了四種或更多現有治療。那是因為新藥實際上風險很大 – 它也會影響健康細胞。這可能導致血小板減少和紅細胞或白細胞等並發症。

“對副作用的擔憂是真實存在的，”負責II期臨床試驗第一部分的教授Dan Vogl說道。 “作為一名患者或作為一名醫生，這不是一種易於服用的藥物。但這種（FDA的）批准是正確的。這是一種藥物，我們可以所有其他治療失敗後提供給患者。”

Selinexor目前正在進行進一步的研究，包括一項3期試驗，該試驗正在測試較低劑量的藥物並將其與另一種常規療法相結合。在其他人中，它正在作為淋巴瘤、白血病和肉瘤的治療方法進行測試。

.(tagsToTranslate)IT 與健康(t)FDA批准了一種有風險的新型抗癌藥物 同時也發出警告(t)kknews.xyz from FDA批准了一種有風險的新型抗癌藥物 同時也發出警告 via KKNEWS

#業內資訊 #FDA批准了一種有風險的新型抗癌藥物 #同時也發出警告

[jorgeiboy23]

Este post lo he subido mientras escucho: Todavía - @matisse_mx ♥️ El mood de la canción me hace recordar esos momentos bonitos haciendo fotografías: @andesthx 🖤 gracias por posar como Diosa ese día, te quiero mucho. @margomuxbal ⚡️ el espacio de ustedes increíble sin palabras. Muchas gracias por ello. . . . . . . #quepeladoguate #talentocreativogt #perhayouneedalittleguatemala #guatemala #chilerograf #instaguate #viajaconnosotrosgt #ownexvision #coquemiraesto #devonartph #soundreel #reelsnation #xpo1 #cuatrogradosnorte (en Margó) https://www.instagram.com/p/CQXTgz4r-JY/?utm_medium=tumblr

#quepeladoguate #talentocreativogt #perhayouneedalittleguatemala #guatemala #chilerograf #instaguate #viajaconnosotrosgt #ownexvision #coquemiraesto #devonartph #soundreel #reelsnation #xpo1 #cuatrogradosnorte

[anti-sjw-kashiyuka]

US Biotech/Pharma Sector Daily Observations Letter: Jan. 25, 2018

Biogen (BIIB) decided to boost its neurological pipeline by acquiring Karyopharm Therapeutics' (KPTI) XPO1 inhibitor neurodegenerative pipeline. Karypharm stock was up more than 12%. Notably, Selenixor, another XOP1 antagonist belonging to Karyopharm is also being tested for cancers like ... from Google Alert - neurological http://ift.tt/2BvbmTl

#IFTTT #Google Alert - neurological

[nightmare-nymph]

Biogen cuts $217n deal for Karyopharm <b>neurology</b> drug

The orally-active candidate, called KPT-350, is a selective inhibitor of nuclear export (SINE) compound that binds to and inhibits a protein called XPO1 which in turn mediates proteins that are believed to play a role in neurological and inflammatory processes. It's the first deal of the year for Biogen but ... from Google Alert - Neurologist http://ift.tt/2ncS7tF

#IFTTT #Google Alert - Neurologist