Showing 1 - 10 of 10 results for "72182"
- ReferenceZhu S et al. (DEC 2010) Cell stem cell 7 6 651--5
Reprogramming of human primary somatic cells by OCT4 and chemical compounds.
Catalog #: Product Name: 72052 CHIR99021 72182 PD0325901 72242 Sodium Butyrate Catalog #: 72052 Product Name: CHIR99021 Catalog #: 72182 Product Name: PD0325901 Catalog #: 72242 Product Name: Sodium Butyrate - ReferenceLin T et al. (NOV 2009) Nature methods 6 11 805--8
A chemical platform for improved induction of human iPSCs.
The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (200-fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, nonviral methods for reprogramming human somatic cells. View PublicationCatalog #: Product Name: 72182 PD0325901 72252 Thiazovivin 72232 SB431542 Catalog #: 72182 Product Name: PD0325901 Catalog #: 72252 Product Name: Thiazovivin Catalog #: 72232 Product Name: SB431542 - ReferenceLi P et al. (DEC 2008) Cell 135 7 1299--310
Germline competent embryonic stem cells derived from rat blastocysts.
Rats have important advantages over mice as an experimental system for physiological and pharmacological investigations. The lack of rat embryonic stem (ES) cells has restricted the availability of transgenic technologies to create genetic models in this species. Here, we show that rat ES cells can be efficiently derived, propagated, and genetically manipulated in the presence of small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine kinases. These rat ES cells express pluripotency markers and retain the capacity to differentiate into derivatives of all three germ layers. Most importantly, they can produce high rates of chimerism when reintroduced into early stage embryos and can transmit through the germline. Establishment of authentic rat ES cells will make possible sophisticated genetic manipulation to create models for the study of human diseases. View PublicationCatalog #: Product Name: 72052 CHIR99021 72182 PD0325901 Catalog #: 72052 Product Name: CHIR99021 Catalog #: 72182 Product Name: PD0325901 - ReferenceBuehr M et al. (DEC 2008) Cell 135 7 1287--98
Capture of authentic embryonic stem cells from rat blastocysts.
Embryonic stem (ES) cells have been available from inbred mice since 1981 but have not been validated for other rodents. Failure to establish ES cells from a range of mammals challenges the identity of cultivated stem cells and our understanding of the pluripotent state. Here we investigated derivation of ES cells from the rat. We applied molecularly defined conditions designed to shield the ground state of authentic pluripotency from inductive differentiation stimuli. Undifferentiated cell lines developed that exhibited diagnostic features of ES cells including colonization of multiple tissues in viable chimeras. Definitive ES cell status was established by transmission of the cell line genome to offspring. Derivation of germline-competent ES cells from the rat paves the way to targeted genetic manipulation in this valuable biomedical model species. Rat ES cells will also provide a refined test-bed for functional evaluation of pluripotent stem cell-derived tissue repair and regeneration. View PublicationCatalog #: Product Name: 72182 PD0325901 Catalog #: 72182 Product Name: PD0325901 - ReferenceLi W et al. (JAN 2009) Cell stem cell 4 1 16--9
Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors.
Catalog #: Product Name: 72052 CHIR99021 72182 PD0325901 Catalog #: 72052 Product Name: CHIR99021 Catalog #: 72182 Product Name: PD0325901 - ReferenceBarrett SD et al. (DEC 2008) Bioorganic & medicinal chemistry letters 18 24 6501--4
The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901.
A novel series of benzhydroxamate esters derived from their precursor anthranilic acids have been prepared and have been identified as potent MEK inhibitors. 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide, CI-1040, was the first MEK inhibitor to demonstrate in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated. Optimization of the diphenylamine core and modification of the hydroxamate side chain for cell potency, solubility, and exposure with oral delivery resulted in the discovery of the clinical candidate N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide PD 0325901. View PublicationCatalog #: Product Name: 72182 PD0325901 Catalog #: 72182 Product Name: PD0325901 - ReferenceSilva J et al. (OCT 2008) PLoS biology 6 10 e253
Promotion of reprogramming to ground state pluripotency by signal inhibition.
Induced pluripotent stem (iPS) cells are generated from somatic cells by genetic manipulation. Reprogramming entails multiple transgene integrations and occurs apparently stochastically in rare cells over many days. Tissue stem cells may be subject to less-stringent epigenetic restrictions than other cells and might therefore be more amenable to deprogramming. We report that brain-derived neural stem (NS) cells acquire undifferentiated morphology rapidly and at high frequency after a single round of transduction with reprogramming factors. However, critical attributes of true pluripotency--including stable expression of endogenous Oct4 and Nanog, epigenetic erasure of X chromosome silencing in female cells, and ability to colonise chimaeras--were not attained. We therefore applied molecularly defined conditions for the derivation and propagation of authentic pluripotent stem cells from embryos. We combined dual inhibition (2i) of mitogen-activated protein kinase signalling and glycogen synthase kinase-3 (GSK3) with the self-renewal cytokine leukaemia inhibitory factor (LIF). The 2i/LIF condition induced stable up-regulation of Oct4 and Nanog, reactivation of the X chromosome, transgene silencing, and competence for somatic and germline chimaerism. Using 2i /LIF, NS cell reprogramming required only 1-2 integrations of each transgene. Furthermore, transduction with Sox2 and c-Myc is dispensable, and Oct4 and Klf4 are sufficient to convert NS cells into chimaera-forming iPS cells. These findings demonstrate that somatic cell state influences requirements for reprogramming and delineate two phases in the process. The ability to capture pre-pluripotent cells that can advance to ground state pluripotency simply and with high efficiency opens a door to molecular dissection of this remarkable phenomenon. View PublicationCatalog #: Product Name: 72182 PD0325901 Catalog #: 72182 Product Name: PD0325901 - ReferenceShi Y et al. (JUN 2008) Cell stem cell 2 6 525--8
A combined chemical and genetic approach for the generation of induced pluripotent stem cells.
Catalog #: Product Name: 72042 BIX01294 72182 PD0325901 Catalog #: 72042 Product Name: BIX01294 Catalog #: 72182 Product Name: PD0325901 - ReferenceYing Q-L et al. (MAY 2008) Nature 453 7194 519--23
The ground state of embryonic stem cell self-renewal.
In the three decades since pluripotent mouse embryonic stem (ES) cells were first described they have been derived and maintained by using various empirical combinations of feeder cells, conditioned media, cytokines, growth factors, hormones, fetal calf serum, and serum extracts. Consequently ES-cell self-renewal is generally considered to be dependent on multifactorial stimulation of dedicated transcriptional circuitries, pre-eminent among which is the activation of STAT3 by cytokines (ref. 8). Here we show, however, that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells. Self-renewal is enabled by the elimination of differentiation-inducing signalling from mitogen-activated protein kinase. Additional inhibition of glycogen synthase kinase 3 consolidates biosynthetic capacity and suppresses residual differentiation. Complete bypass of cytokine signalling is confirmed by isolating ES cells genetically devoid of STAT3. These findings reveal that ES cells have an innate programme for self-replication that does not require extrinsic instruction. This property may account for their latent tumorigenicity. The delineation of minimal requirements for self-renewal now provides a defined platform for the precise description and dissection of the pluripotent state. View PublicationCatalog #: Product Name: 72052 CHIR99021 72162 PD173074 72182 PD0325901 Catalog #: 72052 Product Name: CHIR99021 Catalog #: 72162 Product Name: PD173074 Catalog #: 72182 Product Name: PD0325901 - ReferenceBain J et al. (DEC 2007) The Biochemical journal 408 3 297--315
The selectivity of protein kinase inhibitors: a further update.
The specificities of 65 compounds reported to be relatively specific inhibitors of protein kinases have been profiled against a panel of 70-80 protein kinases. On the basis of this information, the effects of compounds that we have studied in cells and other data in the literature, we recommend the use of the following small-molecule inhibitors: SB 203580/SB202190 and BIRB 0796 to be used in parallel to assess the physiological roles of p38 MAPK (mitogen-activated protein kinase) isoforms, PI-103 and wortmannin to be used in parallel to inhibit phosphatidylinositol (phosphoinositide) 3-kinases, PP1 or PP2 to be used in parallel with Src-I1 (Src inhibitor-1) to inhibit Src family members; PD 184352 or PD 0325901 to inhibit MKK1 (MAPK kinase-1) or MKK1 plus MKK5, Akt-I-1/2 to inhibit the activation of PKB (protein kinase B/Akt), rapamycin to inhibit TORC1 [mTOR (mammalian target of rapamycin)-raptor (regulatory associated protein of mTOR) complex], CT 99021 to inhibit GSK3 (glycogen synthase kinase 3), BI-D1870 and SL0101 or FMK (fluoromethylketone) to be used in parallel to inhibit RSK (ribosomal S6 kinase), D4476 to inhibit CK1 (casein kinase 1), VX680 to inhibit Aurora kinases, and roscovitine as a pan-CDK (cyclin-dependent kinase) inhibitor. We have also identified harmine as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro. The results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes. Despite being used widely, many of the compounds that we analysed were too non-specific for useful conclusions to be made, other than to exclude the involvement of particular protein kinases in cellular processes. View PublicationCatalog #: Product Name: 72052 CHIR99021 72182 PD0325901 72222 SB203580 72682 BIRB-796 72712 BI-D1870 73112 PP1 72102 Dorsomorphin Catalog #: 72052 Product Name: CHIR99021 Catalog #: 72182 Product Name: PD0325901 Catalog #: 72222 Product Name: SB203580 Catalog #: 72682 Product Name: BIRB-796 Catalog #: 72712 Product Name: BI-D1870 Catalog #: 73112 Product Name: PP1 Catalog #: 72102 Product Name: Dorsomorphin
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