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LDN 193189 dihydrochloride
Potent and selective ALK2 and ALK3 inhibitor (IC50 values are 5 and 30 nM, respectively); inhibits BMP4-mediated Smad1/5/8 activation. Exhibits >200-fold selectivity for BMP signaling over TGF-β signaling. Also exhibits selectivity over AMPK, PDGFR and MAPK signaling. Promotes neural induction of hPSCs in combination with SB 431542 (Cat.No. 1614). Also induces differentiation of hPSCs into nociceptive sensory neurons in combination with SB 431542 (Cat.No. 1614), SU 5402 (Cat.No.3300), CHIR 99021 (Cat.No. 4423) and DAPT (Cat.No. 2634).
Sold for research purposes under exclusive agreement from The Brigham and Women's Hospital Inc. US patents 8,507,501 and 9,045,484
Motor neurons differentiated from iPSCs with LDN 193189
Image shows IBJ6 human fibroblast induced pluripotent stem cells which have been differentiated into motor neurons. This was performed using a combination of LDN 193189 (100 nM) and SB 431542 (Cat. No. 1614) followed by Retinoic acid (Cat. No. 0695) and Purmorphamine (Cat. No. 4551) culture on Laminin for 18 days. Commitment to the motor neuron fate was assessed using the motor neuron marker anti-Human Islet-1 (red, R&D Systems®, Cat. No. AF1837) and the general neuronal marker, beta III tubulin (green, R&D Systems®, Cat. No. MAB1195). For visualization, the neurons were stained using Northernlights™ 557-conjugated Donkey anti-Goat Secondary Antibody (R&D Systems®, Cat. No. NL001) and Northernlights™ 493-conjugated Donkey anti-Mouse Secondary Antibody (R&D Systems®, Cat. No. NL009) and counterstained with DAPI (blue, Cat. No. 57
|Storage||Store at -20°C|
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions
The following data is based on the product molecular weight 479.4. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|0.5 mM||4.17 mL||20.86 mL||41.72 mL|
|2.5 mM||0.83 mL||4.17 mL||8.34 mL|
|5 mM||0.42 mL||2.09 mL||4.17 mL|
|25 mM||0.08 mL||0.42 mL||0.83 mL|
References are publications that support the biological activity of the product.
Yu et al (2008) BMP type I receptor inhibition reduces heterotopic ossification. Nat.Med. 14 1363 PMID: 19029982
Chambers et al (2012) Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. Nat.Biotechnol. 30 715 PMID: 22750882
Cuny et al (2008) Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors. Bioorg.Med.Chem.Lett. 18 4388 PMID: 18621530
Li et al (2013) Chemical approaches to stem cell biology and therapeutics. Cell Stem Cell 13 270 PMID: 24012368
Lancaster et al (2015) Generation of Cerebral Organoids from Human Pluripotent Stem Cells Nat. Protoc. 9 2329 PMID: 25188634
Kadoshima et al (2013) Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc.Natl.Acad.Sci.USA. 110 20284 PMID: 24277810
Dye et al (2015) In vitro generation of human pluripotent stem cell derived lung organoids. Elife 4 PMID: 25803487
Wimmer et al (2019) Human blood vessel organoids as a model of diabetic vasculopathy. Nature 565 505 PMID: 30651639
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Keywords: LDN 193189 dihydrochloride, LDN 193189 dihydrochloride supplier, LDN193189, dihydrochloride, BMP, signaling, ALK2, ALK3, activin, bone, morphogenetic, proteins, stem, cells, neural, differentiation, neurons, and, Other, Activin, Receptors, ESCs, iPSC, Neural, Stem, Cells, Organoids, 6053, Tocris Bioscience
6 Citations for LDN 193189 dihydrochloride
Citations are publications that use Tocris products. Selected citations for LDN 193189 dihydrochloride include:
Beraldo et al (2018) Mechanisms of neuroprotection against ischemic insult by stress-inducible phosphoprotein-1/prion protein complex. J Neurochem 145 68 PMID: 29265373
Genga et al (2019) Single-Cell RNA-Sequencing-Based CRISPRi Screening Resolves Molecular Drivers of Early Human Endoderm Development. Cell Rep 27 708 PMID: 30995470
Xiang et al (2019) Long-term functional maintenance of primary human hepatocytes in vitro. Science 364 399 PMID: 31023926
Alsanie (2017) Specification of murine ground state pluripotent stem cells to regional neuronal populations. Sci Rep 7 16001 PMID: 29167563
Young (2017) The doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1. Proc Natl Acad Sci U S A. 114 E5599 PMID: 28655839
Sommer et al (2018) Th17 lymphocytes induce neuronal cell death in a human iPSC-based model of Parkinson's disease. Sell Stem Cell. 23 123 PMID: 29979986
Do you know of a great paper that uses LDN 193189 dihydrochloride from Tocris? Please let us know.
Reviews for LDN 193189 dihydrochloride
Average Rating: 4 (Based on 3 Reviews.)
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To perform inhibition of BMP-like receptors during various interrogations. Performed blanket inhibition of BMP-like receptor kinase activity with 50nM (working) and selective inhibition of ALK3/BMPR1A with 5nM (working) leaving ALK6/BMPR1B active. Non-toxic at concentrations used.
Be wary of storage as activity will degrade over time.
I used the product for 10 days to differentiate ipscs into a neuroepithelium
Tocris Response: Thank you for reviewing our product. Weare sorry that this product did not perform as expected. We have been intouch with the customer to resolve this issue to the customer’s satisfaction
I used it as a BMP pathway inhibitor in Breast cancer Cells. I used the concentration of 100nM and it works really well.
Protocols for LDN 193189 dihydrochloride
The following protocols feature additional information for the use of LDN 193189 dihydrochloride (Cat. No. 6053).
Literature in this Area
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Stem Cells Scientific Review
Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.
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Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.