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E3330 Lorlatinib is an orally active brain penetrant cyclic
2023-11-23
Lorlatinib is an orally active brain penetrant cyclic 2-aminopyridine derivative that is a type I½ B ALK inhibitor (Fig. 5F) [61]. This medicinal is an effective antagonist against the more common L1196M and G1269A crizotinib-resistant mutations as well as the less common T1151Ins, L1152R, C1156Y, F
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Compounds and with potent ALR
2023-11-23
Compounds , and with potent ALR2 inhibitory activity were also tested for their inhibition ability against ALR1, as shown in . They all showed low activity with inhibition percentages no more than 45% at the concentration of 10μM, demonstrating good selectivity for ALR2. To evaluate the antioxida
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Overexpression of AR can lead to
2023-11-23
Overexpression of AR can lead to sorbitol accumulation, leading to diabetic complications (Ransohoff and Cardona, 2010). Therefore, AR is an important enzyme in the growth and development of organisms. With the aim of inhibiting the activity of AR in diabetic patients, screening for inhibitors and i
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br Materials and methods br Results Bilateral microinjection
2023-11-22
Materials and methods Results Bilateral microinjections (n = 6) of 10 mM ACh (300–500 pmol) and 5 mM physostigmine (150–250 pmol) at the two selected caudal NTS sites caused within 1 min significant increases in respiratory frequency (from 54.5 ± 1.7 to 70.9 ± 4.1 breaths/min; +30.8 ± 7.0%; P
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Illustrated in is the protocol we
2023-11-22
Illustrated in is the protocol we applied for the screens of novel furoic acids as ACL inhibitors. We constructed our furan carboxylate library that contained 1446 2-furoic Suramin hexasodium salt mg derivatives and 501 3-furoic acid derivatives by performing substructural searches of the ZINC da
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Having demonstrated that Gq coupled mGluR
2023-11-22
Having demonstrated that Gq-coupled mGluR1a was necessary for estradiol-induced enhancement of CREB phosphorylation, we hypothesized that activation of a separate G-protein signaling pathway could explain the effect of estradiol on L-type calcium channel signaling (Boulware et al., 2005). Indeed, in
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br Introduction Hepatocellular carcinoma HCC is
2023-11-22
Introduction Hepatocellular carcinoma (HCC) is an aggressive and malignant cancer detected in clinical practice, as it is the third key reason of tumor-related deaths worldwide, with > 800, 000 mortalities every year (Torre et al., 2015). Current treatments for HCC are surgical therapy, liver tra
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The levels of Mcl and FLIP are homeostatically
2023-11-22
The levels of Mcl-1 and FLIP are homeostatically controlled by transcriptional and posttranslational processes. Accumulating evidence suggested that intracellular signaling molecules such as Akt are crucial to the transcription of Mcl-1 and FLIP [30], [31]. The constitutive activation of Akt is dete
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In our study caspase and DRAM were identified as
2023-11-22
In our study, caspase3 and DRAM were identified as being involved in full-length AIFM1-induced apoptosis. Caspase3 is best known for its role in the execution phase of apoptosis in both intrinsic and extrinsic apoptotic pathways [17]. The members of the caspase family are generally in inactive pro-f
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membrane transport AP was originally described as a heterodi
2023-11-22
AP-1 was originally described as a heterodimer of the bZIP proteins c-Jun and c-Fos. The experiments described here showed that stimulation of TRPV1 channels induced the expression of both of these classical constituents of AP-1. The essential role of both proteins was analyzed in a series of experi
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br Introduction Active oxygen radicals in the human body
2023-11-22
Introduction Active oxygen radicals in the human body have a strong effect of inducing lipid peroxidation, which in turn induces oxidative imbalance and causes various diseases. Natural polysaccharides are substances with certain antioxidant activity. They are used as antioxidants and have advant
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A requirement for active PKA
2023-11-22
A requirement for active PKA signaling during LTD induction was proposed in studies characterizing AKAP150 D36mice (Lu et al., 2008), but linking impaired LTD in D36 mice to PKA signaling deficits was complicated by subsequent work showing substantial increases in the number of dendritic spines and
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Following activation of mGluRs GRIP stabilized
2023-11-22
Following activation of mGluRs, GRIP-stabilized AMPARs appear to be the primary target for endocytosis. Consistent with this model, we find that using siRNA to reduce GRIP1/2 expression blocks the AMPAR internalization and the synaptic depression mediated by mGluRs. Reductions in GRIP1/2 expression,
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With regard to the correlation between rearrangements and th
2023-11-22
With regard to the correlation between -rearrangements and thromboembolic events, Zer et al. reported a VTE rate of 36% in a cohort of 98 patients with ALK-positive NSCLC. Of note, VTE was also associated with shorter overall survival (HR: 5.71, =0.01) . Only few others have investigated NSCLC drive
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br Introduction The traditional Chinese medicine TCM
2023-11-22
Introduction The traditional Chinese medicine (TCM), Ganoderma (G.) lucidum Karst is a well-known mushroom which has been used clinically in some Asian countries. It is termed “Lingzhi” in China, “Reishi” in Japan and “Yeongji” in Korea. It has long been used in TCM for the promotion of longevit
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