Higher genome mutation rates of Beijing lineage of Mycobacterium tuberculosis during human infection
Mycobacterium tuberculosis (Mtb) strains of Beijing lineage have triggered nice concern due to their fast emergence of drug resistance and worldwide unfold. DNA mutation charges that replicate evolutional adaptation to host responses and the looks of drug resistance haven’t been elucidated in human-infected Beijing strains. We tracked and obtained an authentic Mtb isolate of Beijing lineage from the 1999 tuberculosis outbreak in Japan, in addition to 5 different isolates that unfold in people, and two isolates from the affected person triggered recurrence.
Three isolates have been from sufferers who developed TB inside one 12 months after an infection (rapid-progressor, RP), and the opposite three isolates have been from those that developed TB multiple 12 months after an infection (slow-progressor, SP). We sequenced genomes of those isolates and analyzed the propensity and fee of genomic mutations. Era time versus mutation fee curves have been considerably increased for RP.
The ratio of oxidative versus non-oxidation damages induced mutations was increased in SP than RP, suggesting that persistent Mtb are uncovered to oxidative stress within the latent state. Our knowledge thus demonstrates that increased mutation charges of Mtb Beijing strains throughout human an infection is more likely to account for the upper adaptability and an emergence ratio of drug resistance.
The problem of genetically unresolved haemophilia A sufferers: Curiosity of the mixture of entire F8 gene sequencing and practical assays
Background: The causative variant stays unidentified in 2%-5% of haemophilia A (HA) sufferers regardless of an exhaustive sequencing of the total F8 coding sequence, splice consensus sequences, 5’/3′ untranslated areas and duplicate quantity variant (CNV) evaluation. Subsequent-generation sequencing (NGS) has offered vital enhancements for a whole F8 evaluation.
Goal: The intention of this research was to determine and characterize pathogenic non-coding variants in F8 of 15 French and Canadian HA sufferers genetically unresolved, by means of the usage of NGS, mRNA sequencing and practical affirmation of aberrant splicing.
Strategies: We sequenced your entire F8 gene utilizing an NGS seize methodology. We analysed F8 mRNA to be able to detect aberrant transcripts. The pathogenic impact of candidate intronic variants was additional confirmed utilizing a minigene assay.
Outcomes: After bioinformatic evaluation, 11 deep intronic variants have been recognized in 13 sufferers (eight new variants and three beforehand reported). Three variants have been confirmed to be possible pathogenic with the presence of an aberrant transcript throughout mRNA evaluation and minigene assay. We additionally discovered a small intronic deletion in 6 sufferers, just lately described as inflicting delicate HA.
Conclusion: With this complete work combining NGS and practical assays, we report new deep intronic variants that trigger HA by means of splicing alteration mechanism. Useful analyses are essential to substantiate the pathogenic impact of those variants and shall be invaluable sooner or later to review the big variety of variants of unsure significance that will have an effect on splicing that shall be discovered within the human genome.
The genetic explanation for mental deficiency and/or congenital malformations in two parental reciprocal translocation carriers and implications for assisted replica
Function: To elucidate the genetic explanation for mental deficiency and/or congenital malformations in two parental reciprocal translocation carriers and supply applicable methods of assisted reproductive remedy (ART).
Supplies and strategies: Two comparable {couples} having a toddler with world developmental delay/mental incapacity signs attended the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) in 2017 and 2019, respectively, to be able to decide the trigger(s) of the circumstances affecting their baby and to hunt ART to have a wholesome child. Each of the wholesome {couples} weren’t of consanguineous marriage, denied publicity to toxicants, and had no hostile life historical past.
This research was accredited by the Institutional Ethics Committee of the Reproductive & Genetic Hospital of CITIC-Xiangya, and written knowledgeable consent was obtained from the dad and mom. Genetic diagnoses have been carried out by karyotype evaluation, breakpoint mapping evaluation of chromosomal translocation(s), single-nucleotide polymorphism (SNP) microarray evaluation, and whole-exome sequencing (WES) for the 2 kids and totally different applicable reproductive methods have been carried out within the two households.
Outcomes: Karyotype evaluation revealed that each sufferers carried parental reciprocal translocations [46,XY,t(7;16)(p13;q24)pat and 46,XY,t(13;17)(q12.3;p11.2)pat, respectively]. Comply with-up breakpoint mapping evaluation confirmed no interruption of related genes, and SNP microarray evaluation recognized no vital copy quantity variations (CNVs) within the two sufferers.
Furthermore, WES outcomes revealed that sufferers 1 and a pair of harbored candidate compound heterozygous mutations of MCOLN1 [c.195G>C (p.K65N) and c.1061G>A (p.W354*)] and MCPH1 [c.877A>G (p.S293G) and c.1869_1870delAT (p.C624*)], respectively, that have been inherited from their dad and mom and never beforehand reported. Moreover, the dad and mom of affected person 1 obtained 10 embryos throughout ART cycle, and an embryo of regular karyotype and non-carrier of noticed MCOLN1 mutations in line with preimplantation genetic testing for structural rearrangement and monogenic defect was efficiently transferred, ensuing within the delivery of a wholesome boy. The dad and mom of affected person 2 selected to bear ART with donor sperm to scale back the chance of recurrence.
Conclusions: Systematic genetic prognosis of two carriers of inherited chromosomal translocations accompanied by medical phenotypes revealed their explanation for illness, which was essential for genetic counseling and additional ART for these households.
Mind Community Connectivity and Affiliation with Catechol-O-Methyltransferase Gene Polymorphism in Korean Consideration-Deficit Hyperactivity Dysfunction Kids
Goal: We sought to find out if the hyperlinks between and throughout the default mode community (DMN) and dorsal consideration community (DAT) exhibited totally different circumstances in line with catechol-O-methyltransferase (COMT) gene polymorphism in relationship to attention-deficit hyperactivity dysfunction (ADHD) signs.
Strategies: Fifty-seven kids with ADHD and 48 wholesome controls (HCs) have been administered an intelligence take a look at, the Kids’s Melancholy Stock, the Korean ADHD ranking scale, and steady efficiency take a look at. Resting-state mind practical MRI scans have been obtained, and COMT genotyping was carried out to tell apart valine carriers and methionine homozygotes.
Outcomes: In comparison with controls, kids with ADHD confirmed elevated ADHD scale scores, elevated visible fee errors, and elevated practical connectivity (FC) throughout the DMN and DAT. In comparison with all kids with ADHD, kids with the methionine homozygote and people who have been valine carriers confirmed elevated FC throughout the DMN and DAT and decreased FC between the DMN and DAT. FC throughout the DMN was additionally elevated in HC valine carriers in comparison with HC kids with the methionine homozygote, and in kids with ADHD who have been valine carriers in comparison with HC valine carriers.
Conclusion: We noticed elevated mind connectivity throughout the DMN and DAT and altered mind connectivity inside and between the DMN and DAT related to COMT polymorphism in kids with ADHD.
 ELISA Kit) General Epitestosterone (ET) ELISA Kit |
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| RDR-ET-Ge-48Tests | Reddot Biotech | 48 Tests | EUR 488 |
General Epitestosterone (ET) ELISA Kit |
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| RDR-ET-Ge-96Tests | Reddot Biotech | 96 Tests | EUR 676 |
 Aurora Kinase Inhibitor III |
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| B7947-1 | ApexBio | 1 mg | EUR 179 |
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Description: Aurora Kinase Inhibitor III |
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) Adenosine Kinase Inhibitor (hydrate) |
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| C5282-1 | ApexBio | 1 mg | EUR 112 |
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Description: IC50: 1.7 nM in cell-free assaysAdenosine Kinase Inhibitor is an inhibitor of adenosine kinase. Adenosine kinase is the key metabolizing enzyme regulating cellular adenosine concentrations. |
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 DiscoveryProbe? Kinase Inhibitor Library |
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| L1024-.1 | ApexBio | 100 uL/well(10 mM solution) | EUR 6267 |
 IKK-? Kinase Inhibitor II |
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| 1811-1 | Biovision | EUR 158 | |
 VEGFR Tyrosine Kinase Inhibitor II |
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| C4603-1 | ApexBio | 1 mg | EUR 118 |
 DiscoveryProbe? Tyrosine Kinase Inhibitor Library |
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| L1028-.1 | ApexBio | 100 uL/well(10 mM solution) | EUR 5397 |
 ET-1/ Rat ET- 1 ELISA Kit |
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| ELA-E0482r | Lifescience Market | 96 Tests | EUR 886 |
 Kinase inhibitor-1 |
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| HY-43533 | MedChemExpress | 5mg | EUR 567 |
 HPGDS inhibitor 1 |
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| B1046-1 | ApexBio | 1 mg | EUR 181 |
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Description: HPGDS inhibitor 1 is an oral potent and selective inhibitor of hematopoietic prostaglandin D synthase (HPGDS) with IC50 value of 0.7nM [1].Prostaglandin D2 (PGD2) is a mediator of allergy and inflammation. |
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 TAO Kinase inhibitor 1 |
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| HY-112136 | MedChemExpress | 50mg | EUR 796 |
) MAPKII Kinase Inhibitor (Hsp25 Kinase Inhibitor) |
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| SIH-120A | Stressmarq | 1 mg | EUR 179 |
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Description: The substance MAPKII Kinase Inhibitor is a hsp25 kinase inhibitor. It is synthetically produced and has a purity of >95%. The pure substance is white solid which is soluble in DMSO or H20. |
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 ET-1 Polyclonal Antibody |
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| ES3877-100ul | ELK Biotech | 100ul | EUR 279 |
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Description: A Rabbit Polyclonal antibody against ET-1 from Human. This antibody is tested and validated for WB, ELISA, WB, ELISA |
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ET-1 Polyclonal Antibody |
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| ES3877-50ul | ELK Biotech | 50ul | EUR 207 |
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Description: A Rabbit Polyclonal antibody against ET-1 from Human. This antibody is tested and validated for WB, ELISA, WB, ELISA |
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ET-1 Polyclonal Antibody |
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| ABP52878-003ml | Abbkine | 0.03ml | EUR 158 |
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Description: A polyclonal antibody for detection of ET-1 from Human. This ET-1 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human ET-1 |
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ET-1 Polyclonal Antibody |
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| ABP52878-01ml | Abbkine | 0.1ml | EUR 289 |
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Description: A polyclonal antibody for detection of ET-1 from Human. This ET-1 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human ET-1 |
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ET-1 Polyclonal Antibody |
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| ABP52878-02ml | Abbkine | 0.2ml | EUR 414 |
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Description: A polyclonal antibody for detection of ET-1 from Human. This ET-1 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human ET-1 |
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 Anti-ET-1 antibody |
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| STJ96512 | St John's Laboratory | 200 µl | EUR 197 |
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Description: Rabbit polyclonal to ET-1. |
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ET-1 Polyclonal Antibody |
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| 41562-100ul | SAB | 100ul | EUR 252 |
ET-1 Polyclonal Antibody |
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| 41562-50ul | SAB | 50ul | EUR 187 |
 Antibody) Endothelin 1 (ET-1) Antibody |
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| abx024086-100ug | Abbexa | 100 ug | EUR 940 |
) Sorafenib (Raf-1 kinase inhibitor) |
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| SIH-476-10MG | Stressmarq | 10 mg | EUR 121 |
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Description: The substance Sorafenib is a raf-1 kinase inhibitor. It is synthetically produced and has a purity of >99%. The pure substance is off white powder which is soluble inDMSO (200mg/ml) or ethanol (3mg/ml). |
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Sorafenib (Raf-1 kinase inhibitor) |
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| SIH-476-50MG | Stressmarq | 50 mg | EUR 289 |
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Description: The substance Sorafenib is a raf-1 kinase inhibitor. It is synthetically produced and has a purity of >99%. The pure substance is off white powder which is soluble inDMSO (200mg/ml) or ethanol (3mg/ml). |
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 187-1, N-WASP inhibitor |
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| B5251-1 | ApexBio | 1 mg | EUR 399 |
 p16-INK4a Cyclin-Dependent Kinase Inhibitor 2A Human Recombinant Protein |
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| PROTP42771-1 | BosterBio | Regular: 20ug | EUR 317 |
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Description: CDKN2A Human Recombinant produced in E.Coli, it's a single non-glycosylated polypeptide chain containing 156 amino acids, approximately 16.5 kDa.;CDKN2A is purified by proprietary chromatographic techniques. |
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 Mouse ET-1 ELISA Kit |
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| EME0184 | Abclonal | 96Tests | EUR 521 |
 Porcine ET-1 ELISA Kit |
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| EPE0184 | Abclonal | 96Tests | EUR 521 |
 Rat ET-1 ELISA Kit |
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| ERE0184 | Abclonal | 96Tests | EUR 521 |
 Rabbit ET-1 ELISA Kit |
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| ERTE0184 | Abclonal | 96Tests | EUR 521 |
 Anserini ET-1 ELISA Kit |
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| EAE0184 | Abclonal | 96Tests | EUR 521 |
 Goat ET-1 ELISA Kit |
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| EGTE0184 | Abclonal | 96Tests | EUR 521 |
 Canine ET-1 ELISA Kit |
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| ECE0184 | Abclonal | 96Tests | EUR 521 |
 Human ET-1 ELISA Kit |
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| EHE0184 | Abclonal | 96Tests | EUR 521 |
 Bovine ET-1 ELISA Kit |
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| EBE0184 | Abclonal | 96Tests | EUR 521 |
 ET-1 Polyclonal Conjugated Antibody |
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| C41562 | SAB | 100ul | EUR 397 |
Canine ET-1 ELISA Kit |
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| ELA-E0482d | Lifescience Market | 96 Tests | EUR 928 |
 ELISA Kit) ET-1(Endothelin-1) ELISA Kit |
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| EU0205 | FN Test | 96T | EUR 524.1 |
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Description: Method of detection: Coated with Antigen, Competitive ELISA;Reacts with: General;Sensitivity: 0.625pg/ml |
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 Big ET/ Rat Big ET ELISA Kit |
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| ELA-E0483r | Lifescience Market | 96 Tests | EUR 886 |
) YAP-TEAD Inhibitor 1 (Peptide 17) |
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| A1149-1 | ApexBio | 1 mg | EUR 235 |
 AKT Kinase Inhibitor |
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| HY-10249A | MedChemExpress | 10mg | EUR 877 |
 Tyrosine kinase inhibitor |
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| HY-10421 | MedChemExpress | 25mg | EUR 383 |
 Tie2 kinase inhibitor |
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| E1KS1577 | EnoGene | 10mg | EUR 1541 |
 MAPKII Kinase Inhibitor |
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| abx076811-1mg | Abbexa | 1 mg | EUR 314 |
AKT Kinase Inhibitor |
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| A3150-10 | ApexBio | 10 mg | EUR 1136 |
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Description: AKT Kinase Inhibitor |
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AKT Kinase Inhibitor |
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| A3150-5 | ApexBio | 5 mg | EUR 683 |
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Description: AKT Kinase Inhibitor |
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AKT Kinase Inhibitor |
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| A3150-5.1 | ApexBio | 10 mM (in 1mL DMSO) | EUR 746 |
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Description: AKT Kinase Inhibitor |
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) Dasatinib (Kinase inhibitor) |
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| SIH-440-25MG | Stressmarq | 25 mg | EUR 199 |
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Description: The substance Dasatinib is a kinase inhibitor. It is synthetically produced and has a purity of ?98%. The pure substance is crystalline solid which is soluble in DMSO (200 mg/ml), ethanol (very poorly ), and water (very poorly ). |
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Dasatinib (Kinase inhibitor) |
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| SIH-440-5MG | Stressmarq | 5 mg | EUR 134 |
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Description: The substance Dasatinib is a kinase inhibitor. It is synthetically produced and has a purity of ?98%. The pure substance is crystalline solid which is soluble in DMSO (200 mg/ml), ethanol (very poorly ), and water (very poorly ). |
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) K252A (Kinase inhibitor) |
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| SIH-455-100UG | Stressmarq | 100 µg | EUR 131 |
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Description: The substance K252A is a kinase inhibitor. It is nonomuraea longicatena and has a purity of ?98%. The pure substance is white solid which is soluble to 25 mM in DMSO. |
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K252A (Kinase inhibitor) |
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| SIH-455-1MG | Stressmarq | 1 mg | EUR 299 |
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Description: The substance K252A is a kinase inhibitor. It is nonomuraea longicatena and has a purity of ?98%. The pure substance is white solid which is soluble to 25 mM in DMSO. |
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) K252B (Kinase inhibitor) |
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| SIH-456-100UG | Stressmarq | 100 µg | EUR 182 |
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Description: The substance K252B is a kinase inhibitor. It is synthetically produced and has a purity of ?98%. The pure substance is white solid which is soluble in DMSO (1 mg/ml) or dimethyl formamide (1 mg/ml). |
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K252B (Kinase inhibitor) |
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| SIH-456-1MG | Stressmarq | 1 mg | EUR 569 |
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Description: The substance K252B is a kinase inhibitor. It is synthetically produced and has a purity of ?98%. The pure substance is white solid which is soluble in DMSO (1 mg/ml) or dimethyl formamide (1 mg/ml). |
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) Midostaurin (Kinase inhibitor) |
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| SIH-468-1MG | Stressmarq | 1 mg | EUR 171 |
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Description: The substance Midostaurin is a kinase inhibitor. It is synthetically produced and has a purity of ?98%. The pure substance is white to off-white powder which is soluble in DMSO (15 mg/ml), MDC (10 mg/ml), methanol (5 mg/ml) or 100% ethanol (2.5 mg/ml). |
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Midostaurin (Kinase inhibitor) |
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| SIH-468-5MG | Stressmarq | 5 mg | EUR 507 |
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Description: The substance Midostaurin is a kinase inhibitor. It is synthetically produced and has a purity of ?98%. The pure substance is white to off-white powder which is soluble in DMSO (15 mg/ml), MDC (10 mg/ml), methanol (5 mg/ml) or 100% ethanol (2.5 mg/ml). |
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Tie2 kinase inhibitor |
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| A5979-100 | ApexBio | 100 mg | EUR 1210 |
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Description: IC50: A reversible and selective inhibitor of Tie2 with IC50 of 0.25 M, whose selectivity is 200-fold higher than that of p38. |
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Tie2 kinase inhibitor |
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| A5979-25 | ApexBio | 25 mg | EUR 398 |
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Description: IC50: A reversible and selective inhibitor of Tie2 with IC50 of 0.25 M, whose selectivity is 200-fold higher than that of p38. |
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Tie2 kinase inhibitor |
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| A5979-5 | ApexBio | 5 mg | EUR 166 |
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Description: IC50: A reversible and selective inhibitor of Tie2 with IC50 of 0.25 M, whose selectivity is 200-fold higher than that of p38. |
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Tie2 kinase inhibitor |
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| A5979-5.1 | ApexBio | 10 mM (in 1mL DMSO) | EUR 447 |
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Description: IC50: A reversible and selective inhibitor of Tie2 with IC50 of 0.25 M, whose selectivity is 200-fold higher than that of p38. |
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 Tie2 Kinase Inhibitor |
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| B1338-25 | Biovision | EUR 756 | |
Tie2 Kinase Inhibitor |
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| B1338-5 | Biovision | EUR 262 | |
 p21/Cyclin-Dependent Kinase Inhibitor 1 |
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| MO47036 | Neuromics | 100 ul | EUR 349 |
 Lck Inhibitor |
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| A3539-1 | ApexBio | 1 mg | EUR 154 |
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Description: Lck Inhibitor is a small-molecule inhibitor of with IC50 value of 7 nM [1].The lymphocyte specific kinase which expressed in NK cells and T-cells is a member of the Src kinase family. |
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 NFAT Inhibitor |
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| A4539-1 | ApexBio | 1 mg | EUR 138 |
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Description: Selective inhibitor of calcineurin-mediated dephosphorylation of nuclear factor of activated T cells (NFAT). Does not disrupt other calcineurin-dependent pathways. Inhibits NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells. |
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 EGFR Inhibitor |
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| C3327-1 | ApexBio | 1 mg | EUR 154 |
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Description: EGFR inhibitor is a cell permeable, pyrimidine compound that selectively inhibits the EGFR kinase with IC50 value of 21 nM [1]. EGFR is a transmembrane protein, and is a receptor for members of epidermal growth factor family. |
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 Stat5 Inhibitor |
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| 9484-1 | Biovision | EUR 120 | |
 Chk2 Inhibitor |
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| 1702-1 | Biovision | EUR 180 | |
 SCD1 Inhibitor |
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| 1716-1 | Biovision | EUR 218 | |
 ACC2 Inhibitor |
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| 1717-1 | Biovision | EUR 218 | |
 Syk Inhibitor |
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| 1983-1 | Biovision | EUR 126 | |
) Phosphatase Inhibitor Cocktail 1 (100X in DMSO) |
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| K1012-1 | ApexBio | 1 ml | EUR 102 |
 ET-3 antibody |
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| 22579-100ul | SAB | 100ul | EUR 390 |
 ET-2 Antibody |
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| 35400-100ul | SAB | 100ul | EUR 390 |
 Rabbit Endothelin 1,ET-1 ELISA Kit |
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| GA-E0074RB-48T | GenAsia Biotech | 48T | EUR 326 |
Rabbit Endothelin 1,ET-1 ELISA Kit |
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| GA-E0074RB-96T | GenAsia Biotech | 96T | EUR 524 |
ELISA Kit) Canine Endothelin 1(ET-1)ELISA Kit |
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| GA-E0098CN-48T | GenAsia Biotech | 48T | EUR 402 |
Canine Endothelin 1(ET-1)ELISA Kit |
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| GA-E0098CN-96T | GenAsia Biotech | 96T | EUR 684 |
