LDN 193189 dihydrochloride
Chemical Name: 4-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline dihydrochloride
Biological Activity
LDN 193189 dihydrochloride is a 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).LDN 193189 synthesized to cGMP guidelines also available.
For more information about how LDN 193189 dihydrochloride may be used, see our protocols: Generation of β cells from hPSCs, Generating Midbrain Dopaminergic Neurons from hPSCs, Accelerated Induction of Cortical Neurons from hiPSCs.
Scientific Data
Application of LDN 193189 in motor neurons differentiated from iPSCs. 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 (Catalog # 1614, Tocris) followed by Retinoic acid (Catalog # 0695, Tocris) and Purmorphamine (Catalog # 4551, Tocris) 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, Catalog # AF1837) and the general neuronal marker, beta III tubulin (green, R&D Systems, Catalog # MAB1195). For visualization, the neurons were stained using Northernlights™ 557-conjugated Donkey anti-Goat Secondary Antibody (R&D Systems, Catalog # NL001) and Northernlights™ 493-conjugated Donkey anti-Mouse Secondary Antibody (R&D Systems, Catalog # NL009 NL009) and counterstained with DAPI (blue, Catalog # 5748, Tocris).
Application in motor neurons differentiated from iPSCs
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. 5748).
Technical Data
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.
Additional Information
Background References
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BMP type I receptor inhibition reduces heterotopic ossification.
Yu et al.
Nat.Med., 2008;14:1363 -
Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors.
Chambers et al.
Nat.Biotechnol., 2012;30:715 -
Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors.
Cuny et al.
Bioorg.Med.Chem.Lett., 2008;18:4388 -
Chemical approaches to stem cell biology and therapeutics.
Li et al.
Cell Stem Cell, 2013;13:270 -
Generation of Cerebral Organoids from Human Pluripotent Stem Cells
Lancaster et al.
Nat.Protoc., 2015;9:2329 -
In vitro generation of human pluripotent stem cell derived lung organoids.
Dye et al.
Elife, 2015; -
Human blood vessel organoids as a model of diabetic vasculopathy.
Wimmer et al.
Nature, 2019;565:505 -
Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex.
Kadoshima et al.
Proc.Natl.Acad.Sci.USA., 2013;110:20284
Product Datasheets
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Citations for LDN 193189 dihydrochloride
The citations listed below are publications that use Tocris products. Selected citations for LDN 193189 dihydrochloride include:
7 Citations: Showing 1 - 7
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Robotic high-throughput biomanufacturing and functional differentiation of human pluripotent stem cells.
Authors: Tristan Et al.
Stem Cell Reports 2021;16:3076
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Long-term functional maintenance of primary human hepatocytes in vitro.
Authors: Xiang Et al.
Science 2019;364:399
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Single-Cell RNA-Sequencing-Based CRISPRi Screening Resolves Molecular Drivers of Early Human Endoderm Development.
Authors: Genga Et al.
Cell Rep 2019;27:708
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Th17 lymphocytes induce neuronal cell death in a human iPSC-based model of Parkinson's disease.
Authors: Sommer Et al.
Cell Stem Cell 2018;23:123
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Mechanisms of neuroprotection against ischemic insult by stress-inducible phosphoprotein-1/prion protein complex.
Authors: Beraldo Et al.
J Neurochem 2018;145:68
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Specification of murine ground state pluripotent stem cells to regional neuronal populations.
Authors: Alsanie
Sci Rep 2017;7(1):16001
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The doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1.
Authors: Young
Proc Natl Acad Sci U S A. 2017;114(28):E5599
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I used it as a BMP pathway inhibitor in Breast cancer Cells. I used the concentration of 100nM and it works really well.