Tag: 374.439

Stability indicating RP-HPLC method for determination of glasdegib in bulk and pharmaceutical dosage form was written by Rao, P. Venkateswara;Meghana, P.;Bhavana, J.;Lakshmi, K. Bhagya;Ramya, K.. And the article was included in International Journal of Research in Pharmacy and Chemistry in 2020.Product Details of 1095173-27-5 This article mentions the following:

A simple, rapid, precise, sensitive and reproducible reverse phase high performance liquid chromatog. (RP-HPLC) method has been developed for the quant. anal. of Glasdegib in pharmaceutical dosage form. Chromatog. separation of Glasdegib was achieved on Waters Alliance-e2695, by using Waters Symmetry C18, 150×4.6mm, 3.5渭m column and the mobile phase containing 0.1% TEA adjusting pH=2.5 with OPA & Acetonitrile in the ratio of 90:10% volume/volume The flow rate was 0.5 mL/min; detection was carried out by absorption at 268nm using a photodiode array detector at ambient temperature The number of theor. plates and tailing factor for Glasdegib is NLT 2000 and should not more than 2 resp.% Relative standard deviation of peak areas of all measurements always less than 2.0. The proposed method was validated according to ICH guidelines. The method was found to be simple, economical, suitable, precise, accurate & robust method for quant. anal. of Glasdegib. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Product Details of 1095173-27-5).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Product Details of 1095173-27-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Glasdegib: First Global Approval was written by Hoy, Sheridan M.. And the article was included in Drugs in 2019.HPLC of Formula: 1095173-27-5 This article mentions the following:

Glasdegib (DAURISMO) is an oral inhibitor of the Hedgehog signalling pathway, the activation of which is associated with a number of malignancies. It has been developed by Pfizer and was approved in Nov. 2018 in the USA for use in combination with low-dose cytarabine for the treatment of newly-diagnosed acute myeloid leukemia (AML) in patients aged = 75 years or those who have comorbidities that preclude use of intensive induction chemotherapy. Glasdegib is the first Hedgehog pathway inhibitor to be approved for AML in the USA. It received orphan designation for the treatment of AML in the USA in June 2017 and in the EU in Oct. 2017, and for the treatment of myelodysplastic syndrome (MDS) in the USA in Oct. 2017. It is also undergoing clin. development for use in select haematol. and other malignancies, including MDS, in various countries worldwide. This article summarizes the milestones in the development of glasdegib leading to its use in combination with low-dose cytarabine for the treatment of newly-diagnosed AML in patients aged = 75 years or those who have comorbidities that preclude use of intensive induction chemotherapy. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5HPLC of Formula: 1095173-27-5).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Piperidine derivatives bearing a masked aldehyde function in the 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.HPLC of Formula: 1095173-27-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

GLI2 inhibition abrogates human leukemia stem cell dormancy was written by Sadarangani, Anil;Pineda, Gabriel;Lennon, Kathleen M.;Chun, Hye-Jung;Shih, Alice;Schairer, Annelie E.;Court, Angela C.;Goff, Daniel J.;Prashad, Sacha L.;Geron, Ifat;Wall, Russell;McPherson, John D.;Moore, Richard A.;Pu, Minya;Bao, Lei;Jackson-Fisher, Amy;Munchhof, Michael;Van Arsdale, Todd;Reya, Tannishtha;Morris, Sheldon R.;Minden, Mark D.;Messer, Karen;Mikkola, Hanna K. A.;Marra, Marco A.;Hudson, Thomas J.;Jamieson, Catriona H. M.. And the article was included in Journal of Translational Medicine in 2015.Category: piperidines This article mentions the following:

Dormant leukemia stem cells LSC promote therapeutic resistance and leukemic progression as a result of unbridled activation of stem cell gene expression programs. Thus, we hypothesized that (1) deregulation of the Hedgehog Hh stem cell self-renewal and cell cycle regulatory pathway would promote dormant human LSC generation and (2) that PF- 04449913, a clin. antagonist of the GLI2 transcriptional activator, smoothened SMO, would enhance dormant human LSC eradication. To test these postulates, whole transcriptome RNA sequencing RNA-seq, microarray, qRT-PCR, stromal co-culture, confocal fluorescence microscopic, nanoproteomic, serial transplantation and cell cycle analyses were performed on FACS purified normal, chronic phase CP chronic myeloid leukemia CML, blast crisis BC phase CML progenitors with or without PF-04449913 treatment. Notably, RNA-seq analyses revealed that Hh pathway and cell cycle regulatory gene overexpression correlated with leukemic progression. While lentivirally enforced GLI2 expression enhanced leukemic progenitor dormancy in stromal co-cultures, this was not observed with a mutant GLI2 lacking a transactivation domain, suggesting that GLI2 expression prevented cell cycle transit. Selective SMO inhibition with PF-04449913 in humanized stromal co-cultures and LSC xenografts reduced downstream GLI2 protein and cell cycle regulatory gene expression. Moreover, SMO inhibition enhanced cell cycle transit and sensitized BC LSC to tyrosine kinase inhibition in vivo at doses that spare normal HSC. In summary, while GLI2, forms part of a core HH pathway transcriptional regulatory network that promotes human myeloid leukemic progression and dormant LSC generation, selective inhibition with PF-04449913 reduces the dormant LSC burden thereby providing a strong rationale for clin. trials predicated on SMO inhibition in combination with TKIs or chemotherapeutic agents with the ultimate aim of obviating leukemic therapeutic resistance, persistence and progression. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Category: piperidines).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML was written by Jaramillo, Sonia;Krisam, Johannes;Le Cornet, Lucian;Kratzmann, Markus;Baumann, Lukas;Sauer, Tim;Crysandt, Martina;Rank, Andreas;Behringer, Dirk;Teichmann, Lino;Goerner, Martin;Trappe, Ralf-Ulrich;Roellig, Christoph;Krause, Stefan;Hanoun, Maher;Hopfer, Olaf;Held, Gerhard;Buske, Sebastian;Fransecky, Lars;Kayser, Sabine;Schliemann, Christoph;Schaefer-Eckart, Kerstin;Al-Fareh, Yousef;Schubert, Joerg;Geer, Thomas;Kaufmann, Martin;Brecht, Arne;Niemann, Dirk;Kieser, Meinhard;Bornhaeuser, Martin;Platzbecker, Uwe;Serve, Hubert;Baldus, Claudia D.;Mueller-Tidow, Carsten;Schlenk, Richard F.. And the article was included in Trials in 2021.Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea This article mentions the following:

Overall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after 5 years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-mol. inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone. These findings warrant further investigations in the phase III GnG trial. This is a randomized phase III trial with measurable residual disease (MRD) after induction therapy and event-free survival (EFS) as primary endpoints. The two research questions are addressed in a 2 by 2 factorial design. Patients age 60 years and older are upfront randomized 1:1 in one of the two induction arms: GO administered to intensive induction therapy on days 1,4, and 7 vs. GO administered once on day 1 (GO-147 vs. GO-1), and double-blinded 1:1 in one of the subsequent treatment arms glasdegib vs. placebo as adjunct to consolidation therapy and as single-agent maintenance therapy for six months. Chemotherapy backbone for induction therapy consists of standard 7 + 3 schedule with cytarabine 200 mg/m2 continuously days 1 to 7, daunorubicin 60 mg/m2 days 1, 2, and 3 and high-dose cytarabine (1 g/m2, bi-daily, days 1, 2, and 3) for consolidation therapy. Addressing two primary endpoints, MRD-negativity after induction therapy and event-free survival (EFS), 252 evaluable patients are needed to reject each of the two null hypotheses at a two-sided significance level of 2.5% with a power of at least 85%. Ethics and dissemination: Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Piperidine derivatives are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Molecularly targeted therapy, from the past to the near future was written by Hosono, Naoko. And the article was included in Igaku no Ayumi in 2021.Reference of 1095173-27-5 This article mentions the following:

Mol.-targeted drugs for leukemia have made remarkable progress in recent years. As the gene mutations involved in the development of leukemia and their hierarchical structure have been clarified, the development of low-mol.-weight compounds targeting the mutant genes has also made remarkable progress and in the United States, the hedgehog inhibitor mutant isocitrate dehydrogenase Enzyme (IDH) inhibitor, approval of oral methylation inhibitors has been obtained for acute myeloid leukemia (AML), and approval in Japan is awaited. Clin. trials of promising drugs for refractory leukemia, such as TP53 reactivating drugs and cyclin-dependent kinases, are also underway. Initially, antibody drugs focused only on leukemia tumor cells, but with the success of bispecific T-cell induction (BITE) antibodies in acute lymphocytic leukemia (ALL), leukemia stem cells Development of antibody drugs targeting leukemia and antibody drugs that suppress immune tolerance and induce phagocytosis of macrophages is underway. Leukemia treatment has long been centered on cell-killing antitumor agents, but is now at a turning point with the development of science. This paper outlines the current status and prospects of the development of mol.-targeted drugs for acute leukemia, which is considered to be the hottest topic at present. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Reference of 1095173-27-5).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Reference of 1095173-27-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

New directions for emerging therapies in acute myeloid leukemia: the next chapter. was written by Daver, Naval;Wei, Andrew H;Pollyea, Daniel A;Fathi, Amir T;Vyas, Paresh;DiNardo, Courtney D. And the article was included in Blood cancer journal in 2020.Related Products of 1095173-27-5 This article mentions the following:

Conventional therapy for acute myeloid leukemia is composed of remission induction with cytarabine- and anthracycline-containing regimens, followed by consolidation therapy, including allogeneic stem cell transplantation, to prolong remission. In recent years, there has been a significant shift toward the use of novel and effective, target-directed therapies, including inhibitors of mutant FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase (IDH), the B-cell lymphoma 2 inhibitor venetoclax, and the hedgehog pathway inhibitor glasdegib. In older patients the combination of a hypomethylating agent or low-dose cytarabine, venetoclax achieved composite response rates that approximate those seen with standard induction regimens in similar populations, but with potentially less toxicity and early mortality. Preclinical data suggest synergy between venetoclax and FLT3- and IDH-targeted therapies, and doublets of venetoclax with inhibitors targeting these mutations have shown promising clinical activity in early stage trials. Triplet regimens involving the hypomethylating agent and venetoclax with FLT3 or IDH1/2 inhibitor, the TP53-modulating agent APR-246 and magrolimab, myeloid cell leukemia-1 inhibitors, or immune therapies such as CD123 antibody-drug conjugates and programmed cell death protein 1 inhibitors are currently being evaluated. It is hoped that such triplets, when applied in appropriate patient subsets, will further enhance remission rates, and more importantly remission durations and survival. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Related Products of 1095173-27-5).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Related Products of 1095173-27-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Molecularly targeted therapy, from the past to the near future was written by Hosono, Naoko. And the article was included in Igaku no Ayumi in 2021.Reference of 1095173-27-5 This article mentions the following:

Mol.-targeted drugs for leukemia have made remarkable progress in recent years. As the gene mutations involved in the development of leukemia and their hierarchical structure have been clarified, the development of low-mol.-weight compounds targeting the mutant genes has also made remarkable progress and in the United States, the hedgehog inhibitor mutant isocitrate dehydrogenase Enzyme (IDH) inhibitor, approval of oral methylation inhibitors has been obtained for acute myeloid leukemia (AML), and approval in Japan is awaited. Clin. trials of promising drugs for refractory leukemia, such as TP53 reactivating drugs and cyclin-dependent kinases, are also underway. Initially, antibody drugs focused only on leukemia tumor cells, but with the success of bispecific T-cell induction (BITE) antibodies in acute lymphocytic leukemia (ALL), leukemia stem cells Development of antibody drugs targeting leukemia and antibody drugs that suppress immune tolerance and induce phagocytosis of macrophages is underway. Leukemia treatment has long been centered on cell-killing antitumor agents, but is now at a turning point with the development of science. This paper outlines the current status and prospects of the development of mol.-targeted drugs for acute leukemia, which is considered to be the hottest topic at present. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Reference of 1095173-27-5).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Reference of 1095173-27-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

GLI2 inhibition abrogates human leukemia stem cell dormancy was written by Sadarangani, Anil;Pineda, Gabriel;Lennon, Kathleen M.;Chun, Hye-Jung;Shih, Alice;Schairer, Annelie E.;Court, Angela C.;Goff, Daniel J.;Prashad, Sacha L.;Geron, Ifat;Wall, Russell;McPherson, John D.;Moore, Richard A.;Pu, Minya;Bao, Lei;Jackson-Fisher, Amy;Munchhof, Michael;Van Arsdale, Todd;Reya, Tannishtha;Morris, Sheldon R.;Minden, Mark D.;Messer, Karen;Mikkola, Hanna K. A.;Marra, Marco A.;Hudson, Thomas J.;Jamieson, Catriona H. M.. And the article was included in Journal of Translational Medicine in 2015.Category: piperidines This article mentions the following:

Dormant leukemia stem cells LSC promote therapeutic resistance and leukemic progression as a result of unbridled activation of stem cell gene expression programs. Thus, we hypothesized that (1) deregulation of the Hedgehog Hh stem cell self-renewal and cell cycle regulatory pathway would promote dormant human LSC generation and (2) that PF- 04449913, a clin. antagonist of the GLI2 transcriptional activator, smoothened SMO, would enhance dormant human LSC eradication. To test these postulates, whole transcriptome RNA sequencing RNA-seq, microarray, qRT-PCR, stromal co-culture, confocal fluorescence microscopic, nanoproteomic, serial transplantation and cell cycle analyses were performed on FACS purified normal, chronic phase CP chronic myeloid leukemia CML, blast crisis BC phase CML progenitors with or without PF-04449913 treatment. Notably, RNA-seq analyses revealed that Hh pathway and cell cycle regulatory gene overexpression correlated with leukemic progression. While lentivirally enforced GLI2 expression enhanced leukemic progenitor dormancy in stromal co-cultures, this was not observed with a mutant GLI2 lacking a transactivation domain, suggesting that GLI2 expression prevented cell cycle transit. Selective SMO inhibition with PF-04449913 in humanized stromal co-cultures and LSC xenografts reduced downstream GLI2 protein and cell cycle regulatory gene expression. Moreover, SMO inhibition enhanced cell cycle transit and sensitized BC LSC to tyrosine kinase inhibition in vivo at doses that spare normal HSC. In summary, while GLI2, forms part of a core HH pathway transcriptional regulatory network that promotes human myeloid leukemic progression and dormant LSC generation, selective inhibition with PF-04449913 reduces the dormant LSC burden thereby providing a strong rationale for clin. trials predicated on SMO inhibition in combination with TKIs or chemotherapeutic agents with the ultimate aim of obviating leukemic therapeutic resistance, persistence and progression. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Category: piperidines).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML was written by Jaramillo, Sonia;Krisam, Johannes;Le Cornet, Lucian;Kratzmann, Markus;Baumann, Lukas;Sauer, Tim;Crysandt, Martina;Rank, Andreas;Behringer, Dirk;Teichmann, Lino;Goerner, Martin;Trappe, Ralf-Ulrich;Roellig, Christoph;Krause, Stefan;Hanoun, Maher;Hopfer, Olaf;Held, Gerhard;Buske, Sebastian;Fransecky, Lars;Kayser, Sabine;Schliemann, Christoph;Schaefer-Eckart, Kerstin;Al-Fareh, Yousef;Schubert, Joerg;Geer, Thomas;Kaufmann, Martin;Brecht, Arne;Niemann, Dirk;Kieser, Meinhard;Bornhaeuser, Martin;Platzbecker, Uwe;Serve, Hubert;Baldus, Claudia D.;Mueller-Tidow, Carsten;Schlenk, Richard F.. And the article was included in Trials in 2021.Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea This article mentions the following:

Overall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after 5 years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-mol. inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone. These findings warrant further investigations in the phase III GnG trial. This is a randomized phase III trial with measurable residual disease (MRD) after induction therapy and event-free survival (EFS) as primary endpoints. The two research questions are addressed in a 2 by 2 factorial design. Patients age 60 years and older are upfront randomized 1:1 in one of the two induction arms: GO administered to intensive induction therapy on days 1,4, and 7 vs. GO administered once on day 1 (GO-147 vs. GO-1), and double-blinded 1:1 in one of the subsequent treatment arms glasdegib vs. placebo as adjunct to consolidation therapy and as single-agent maintenance therapy for six months. Chemotherapy backbone for induction therapy consists of standard 7 + 3 schedule with cytarabine 200 mg/m2 continuously days 1 to 7, daunorubicin 60 mg/m2 days 1, 2, and 3 and high-dose cytarabine (1 g/m2, bi-daily, days 1, 2, and 3) for consolidation therapy. Addressing two primary endpoints, MRD-negativity after induction therapy and event-free survival (EFS), 252 evaluable patients are needed to reject each of the two null hypotheses at a two-sided significance level of 2.5% with a power of at least 85%. Ethics and dissemination: Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Piperidine derivatives are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

New directions for emerging therapies in acute myeloid leukemia: the next chapter. was written by Daver, Naval;Wei, Andrew H;Pollyea, Daniel A;Fathi, Amir T;Vyas, Paresh;DiNardo, Courtney D. And the article was included in Blood cancer journal in 2020.Related Products of 1095173-27-5 This article mentions the following:

Conventional therapy for acute myeloid leukemia is composed of remission induction with cytarabine- and anthracycline-containing regimens, followed by consolidation therapy, including allogeneic stem cell transplantation, to prolong remission. In recent years, there has been a significant shift toward the use of novel and effective, target-directed therapies, including inhibitors of mutant FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase (IDH), the B-cell lymphoma 2 inhibitor venetoclax, and the hedgehog pathway inhibitor glasdegib. In older patients the combination of a hypomethylating agent or low-dose cytarabine, venetoclax achieved composite response rates that approximate those seen with standard induction regimens in similar populations, but with potentially less toxicity and early mortality. Preclinical data suggest synergy between venetoclax and FLT3- and IDH-targeted therapies, and doublets of venetoclax with inhibitors targeting these mutations have shown promising clinical activity in early stage trials. Triplet regimens involving the hypomethylating agent and venetoclax with FLT3 or IDH1/2 inhibitor, the TP53-modulating agent APR-246 and magrolimab, myeloid cell leukemia-1 inhibitors, or immune therapies such as CD123 antibody-drug conjugates and programmed cell death protein 1 inhibitors are currently being evaluated. It is hoped that such triplets, when applied in appropriate patient subsets, will further enhance remission rates, and more importantly remission durations and survival. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Related Products of 1095173-27-5).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Related Products of 1095173-27-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem