Category: 5291-32-7

Related Products of 5291-32-7, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.5291-32-7, Name is APR-246, molecular formula is C10H17NO3. In a article£¬once mentioned of 5291-32-7

Mutant p53 tunes the NRF2-dependent antioxidant response to support survival of cancer cells

NRF2 (NFE2L2) is one of the main regulators of the antioxidant response of the cell. Here we show that in cancer cells NRF2 targets are selectively upregulated or repressed through a mutant p53-dependent mechanism. Mechanistically, mutant p53 interacts with NRF2, increases its nuclear presence and resides with NRF2 on selected ARE containing gene promoters activating the transcription of a specific set of genes while leading to the transcriptional repression of others. We show that thioredoxin (TXN) is a mutant p53-activated NRF2 target with pro-survival and pro-migratory functions in breast cancer cells under oxidative stress, while heme oxygenase 1 (HMOX1) is a mutant p53-repressed target displaying opposite effects. A gene signature of NRF2 targets activated by mutant p53 shows a significant association with bad overall prognosis and with mutant p53 status in breast cancer patients. Concomitant inhibition of thioredoxin system with Auranofin and of mutant p53 with APR-246 synergizes in killing cancer cells expressing p53 gain-of-function mutants.

Note that a catalyst decreases the activation energy for both the forward and the reverse reactions and hence accelerates both the forward and the reverse reactions.Related Products of 5291-32-7, you can also check out more blogs aboutRelated Products of 5291-32-7

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H172N | ChemSpider

Let¡¯s face it, organic chemistry can seem difficult to learn. Especially from a beginner¡¯s point of view. Like 123536-14-1, Name is (R)-3-Aminoquinuclidine dihydrochloride. In a document type is Article, introducing its new discovery., Product Details of 123536-14-12

PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by induction of p73 and noxa

Targeting p53 by the small-molecule PRIMA-1Met/APR-246 has shown promising preclinical activity in various cancer types.However, the mechanism of PRIMA-1Met-induced apoptosis is not completely understood and its effect on multiple myeloma cells is unknown. In this study, we evaluated antitumor effect of PRIMA-1Met alone or its combination with current antimyeloma agents in multiple myeloma cell lines, patient samples, and a mouse xenograft model. Results of our study showed that PRIMA-1Met decreased the viability of multiple myeloma cells irrespective of p53 status, with limited cytotoxicity toward normal hematopoietic cells. Treatment of multiple myeloma cells with PRIMA-1Met resulted in induction of apoptosis, inhibition of colony formation, and migration. PRIMA-1Met restored wild-type conformation of mutant p53 and induced activation of p73 upregulating Noxa and downregulating Mcl-1 without significant modulation of p53 level. siRNAmediated silencing of p53 showed a little effect on apoptotic response of PRIMA-1Met, whereas knockdown of p73 led to substantial attenuation of apoptotic activity in multiple myeloma cells, indicating that PRIMA-1Met- induced apoptosis is, at least in part, p73-dependent.Importantly, PRIMA-1Met delayed tumor growth and prolonged survival of mice bearing multiple myeloma tumor. Furthermore, combined treatment of PRIMA-1Met with dexamethasone or doxorubicin displayed synergistic effects in both multiple myeloma cell lines and primary multiple myeloma samples. Consistent with our in vitro observations, cotreatment with PRIMA-1Met and dexamethasone resulted in enhanced antitumor activity in vivo. Our study for the first time shows antimyeloma activity of PRIMA-1Met and provides the rationale for its clinical evaluation in patients with multiple myeloma, including the high-risk group with p53 mutation/deletion. Mol Cancer Ther; 12(11); 2331-41.

Do you like my blog? If you like, you can also browse other articles about this kind. Thanks for taking the time to read the blog about 5291-32-7

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H174N | ChemSpider

5291-32-7, Name is APR-246, belongs to quinuclidine compound, is a common compound. name: APR-246In an article, once mentioned the new application about 5291-32-7.

USE OF ERIBULIN AND 3-QUINUCLIDINONE DERIVATIVES IN THE TREATMENT OF CANCER

The invention features methods for treating and preventing cancer (e.g., a p53-mutated cancer) in a patient in need thereof by administering eribulin (e.g., eribulin mesylate) in combination with a 3-quinuclidinone derivative (e.g., PRIMA-1 or PRIMA-1MET).

Do you like my blog? If you like, you can also browse other articles about this kind. Thanks for taking the time to read the blog about 5291-32-7

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H164N | ChemSpider

An article , which mentions 5291-32-7, molecular formula is C10H17NO3. The compound – APR-246 played an important role in people’s production and life., Safety of APR-246

NEW STRATEGIES FOR TREATING MELANOMA

The present invention relates to a p53-activating agent capable of transferring wild-type tumor protein p53 (p53) from an inactive conformation into an active conformation capable of inducing apoptosis, for use in the treatment of melanoma, wherein said p53-activating agent is administered simultaneously or sequentially with a BRAF-inhibiting agent capable of inhibiting activity of serine/threonine-protein kinase B-Raf (BRAF) comprising an activating mutation.

Enzymes are biological catalysts that produce large increases in reaction rates and tend to be specific for certain reactants and products. I hope my blog about is helpful to your research. Safety of APR-246

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H166N | ChemSpider

Chemistry is an experimental science, and the best way to enjoy it and learn about it is performing experiments. SDS of cas: 5291-32-7. Introducing a new discovery about 5291-32-7, Name is APR-246

SLMP53-2 restoreswild-type-like function to mutant p53 through hsp70: Promising activity in hepatocellular carcinoma

Half of human cancers harbor TP53 mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds as mutp53 reactivators and anticancer agents was investigated in human tumor cells and xenograft mouse models. By analysis of their anti-proliferative effect on a panel of p53-null NCI-H1299 tumor cells ectopically expressing highly prevalent mutp53, the compound SLMP53-2 was selected based on its potential reactivation of multiple structuralmutp53. In mutp53-Y220C-expressing hepatocellular carcinoma (HCC) cells, SLMP53-2-induced growth inhibition was mediated by cell cycle arrest, apoptosis, and endoplasmic reticulum stress response. In these cells, SLMP53-2 restored wild-type-like conformation and DNA-binding ability of mutp53-Y220C by enhancing its interaction with the heat shock protein 70 (Hsp70), leading to the reestablishment of p53 transcriptional activity. Additionally, SLMP53-2 displayed synergistic effect with sorafenib, the only approved therapy for advanced HCC. Notably, it exhibited potent antitumor activity in human HCC xenograft mouse models with a favorable toxicological profile. Collectively, SLMP53-2 is a new mutp53-targeting agent with promising antitumor activity, particularly against HCC.

We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 5291-32-7, and how the biochemistry of the body works.SDS of cas: 5291-32-7

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H169N | ChemSpider

In heterogeneous catalysis, the catalyst is in a different phase from the reactants. Safety of APR-246, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 5291-32-7, name is APR-246. In an article£¬Which mentioned a new discovery about 5291-32-7

Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL

T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. Here we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identify novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor/cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM toward a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.

Do you like my blog? If you like, you can also browse other articles about this kind. Thanks for taking the time to read the blog about 5291-32-7

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H175N | ChemSpider

Reference of 5291-32-7, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.5291-32-7, Name is APR-246, molecular formula is C10H17NO3. In a article£¬once mentioned of 5291-32-7

APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase

The low-molecular-weight compound APR-246 (PRIMA-1MET) restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. We show here that APR-246 also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance. APR-246 inhibited both recombinant TrxR1 in vitro and TrxR1 in cells. A Sec-to-Cys mutant of TrxR1 was not inhibited by APR-246, suggesting targeting of the selenocysteine residue in wild-type TrxR1. Preheated APR-246 and its conversion product methylene quinuclidinone (MQ) were much more efficient TrxR1 inhibitors than APR-246 itself, indicating that MQ is the active compound responsible for TrxR1 enzyme inhibition. TrxR1 inhibited by MQ was still functional as a pro-oxidant NADPH oxidase. Knockdown of TrxR1 caused a partial and reproducible attenuation of APR-246- induced tumor cell death independently of p53 status. Cellular TrxR1 activity was also inhibited by APR-246 irrespective of p53 status. We show that APR-246 can directly affect cellular redox status via targeting of TrxR1. Our findings provide an explanation for the previously observed effects of APR-246 on tumor cells lacking mutant p53.

Reference of 5291-32-7, Interested yet? Read on for other articles about Reference of 5291-32-7!

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H173N | ChemSpider

Let¡¯s face it, organic chemistry can seem difficult to learn. Especially from a beginner¡¯s point of view. Like 123536-14-1, Name is (R)-3-Aminoquinuclidine dihydrochloride. In a document type is Article, introducing its new discovery., Product Details of 123536-14-13

The benefit of reactivating p53 under MAPK inhibition on the efficacy of radiotherapy in melanoma

Radiotherapy (RT) in patients with melanoma historically showed suboptimal results, because the disease is often radioresistant due to various mechanisms such as scavenging free radicals by thiols, pigmentary machinery, or enhanced DNA repair. However, radiotherapy has been utilized as adjuvant therapy after the complete excision of primary melanoma and lymph nodes to reduce the rate of nodal recurrences in high-risk patients. The resistance of melanoma cells to radiotherapy may also be in relation with the constitutive activation of the MAPK pathway and/or with the inactivation of p53 observed in about 90% of melanomas. In this study, we aimed to assess the potential benefit of adding RT to BRAF-mutated melanoma cells under a combined p53 reactivation and MAPK inhibition in vitro and in a preclinical animal model. We found that the combination of BRAF inhibition (vemurafenib, which completely shuts down the MAPK pathway), together with p53 reactivation (PRIMA-1Met) significantly enhanced the radiosensitivity of BRAF-mutant melanoma cells. This was accompanied by an increase in both p53 expression and activity. Of note, we found that radiation alone markedly promoted both ERK and AKT phosphorylation, thus contributing to radioresistance. The combination of vemurafenib and PRIMA-1Met caused the inactivation of both MAPK kinase and PI3K/AKT pathways. Furthermore, when combined with radiotherapy, it was able to significantly enhance melanoma cell radiosensitivity. Interestingly, in nude mice bearing melanoma xenografts, the latter triple combination had not only a synergistic effect on tumor growth inhibition, but also a potent control on tumor regrowth in all animals after finishing the triple combination therapy. RT alone had only a weak effect. In conclusion, we provide a basis for a strategy that may overcome the radioresistance of BRAF-mutated melanoma cells to radiotherapy. Whether this will translate into a rational to use radiotherapy in the curative setting in BRAF-mutated melanoma patients deserves consideration.

Note that a catalyst decreases the activation energy for both the forward and the reverse reactions and hence accelerates both the forward and the reverse reactions.name: APR-246, you can also check out more blogs aboutname: APR-246

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H171N | ChemSpider

5291-32-7, Name is APR-246, belongs to quinuclidine compound, is a common compound. COA of Formula: C10H17NO3In an article, once mentioned the new application about 5291-32-7.

Piperlongumine and p53-reactivator APR-246 selectively induce cell death in HNSCC by targeting GSTP1

TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC) patients without human papillomavirus infection. The recurrence rate for these patients is distinctly high. It has been actively explored to identify agents that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC. PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its methylated analogue PRIMA-1Met (also called APR-246) were found to be able to reestablish the DNA-binding activity of p53 mutants and reinstate the functions of WT p53. Herein we report that piperlongumine (PL), an alkaloid isolated from Piper longum L., synergizes with APR-246 to selectively induce apoptosis and autophagic cell death in HNSCC cells, whereas primary and immortalized mouse embryonic fibroblasts and spontaneously immortalized non-tumorigenic human skin keratinocytes (HaCat) are spared from the damage by the co-treatment. Interestingly, PL-sensitized HNSCC cells to APR-246 are TP53 mutation-independent. Instead, we demonstrated that glutathione S-transferase pi 1 (GSTP1), a GST family member that catalyzes the conjugation of GSH with electrophilic compounds to fulfill its detoxification function, is highly expressed in HNSCC tissues. Administration of PL and APR-246 significantly suppresses GSTP1 activity, resulting in the accumulation of ROS, depletion of GSH, elevation of GSSG, and DNA damage. Ectopic expression of GSTP1 or pre-treatment with antioxidant N-acetyl-l-cysteine (NAC) abrogates the ROS elevation and decreases DNA damage, apoptosis, and autophagic cell death prompted by PL/APR-246. In addition, administration of PL and APR-246 impedes UMSCC10A xenograft tumor growth in SCID mice. Taken together, our data suggest that HNSCC cells are selectively sensitive to the combination of PL and APR-246 due to a remarkably synergistic effect of the co-treatment in the induction of ROS by suppression of GSTP1.

Note that a catalyst decreases the activation energy for both the forward and the reverse reactions and hence accelerates both the forward and the reverse reactions.COA of Formula: C10H17NO3, you can also check out more blogs aboutCOA of Formula: C10H17NO3

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H170N | ChemSpider

In heterogeneous catalysis, the catalyst is in a different phase from the reactants. HPLC of Formula: C10H17NO3, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 5291-32-7, name is APR-246. In an article£¬Which mentioned a new discovery about 5291-32-7

Efficacy of glutathione inhibitors for the treatment of ARID1A-deficient diffuse-type gastric cancers

ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, increases the intracellular levels of glutathione (GSH) by upregulating solute carrier family 7 member 11 (SLC7A11). Diffuse-type gastric cancer is an aggressive tumor that is frequently associated with ARID1A deficiency. Here, we investigated the efficacy of GSH inhibition for the treatment of diffuse-type gastric cancer with ARID1A deficiency using ARID1A-proficient or -deficient patient-derived cells (PDCs). ARID1A-deficient PDCs were selectively sensitive to the GSH inhibitor APR-246, the GCLC inhibitor buthionine sulfoximine, and the SLC7A11 inhibitor erastin. Expression of SLC7A11, which is required for incorporation of cystine, and the basal level of GSH were lower in ARID1A-deficient than in ARID1A-proficient PDCs. Treatment with APR-246 decreased intracellular GSH levels, leading to the excessive production of reactive oxygen species (ROS), and these phenotypes are suppressed by supply of cystine and GSH compensators. Taken together, vulnerability of ARID1A-deficient gastric cancer cells to GSH inhibition is caused by decreased GSH synthesis due to diminished SLC7A11 expression. The present results suggest that GSH inhibition is a promising strategy for the treatment of diffuse-type gastric cancers with ARID1A deficiency.

Enzymes are biological catalysts that produce large increases in reaction rates and tend to be specific for certain reactants and products. I hope my blog about is helpful to your research. HPLC of Formula: C10H17NO3

Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H168N | ChemSpider