LDN 193189 dihydrochloride
Chemical Name: 4-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline dihydrochloride
Purity: ≥98%
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 and LDN 193189 in solution 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).
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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Evidence of In�Vitro Preservation of Human Nephrogenesis at the Single-Cell Level
N Pode-Shakk, R Gershon, G Tam, D Omer, Y Gnatek, I Kanter, S Oriel, G Katz, O Harari-Ste, T Kalisky, B Dekel
Stem Cell Reports, 2017;0(0):. -
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
Citations for LDN 193189 dihydrochloride
The citations listed below are publications that use Tocris products. Selected citations for LDN 193189 dihydrochloride include:
37 Citations: Showing 1 - 10
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A Robust Pipeline for the Multi-Stage Accelerated Differentiation of Functional 3D Cortical Organoids from Human Pluripotent Stem Cells.
Authors: Mustafa Et al.
Curr Protoc 2023;3:e641
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Expansion of ventral foregut is linked to changes in the enhancer landscape for organ-specific differentiation.
Authors: Sara Et al.
Nat Cell Biol 2023;25:481-492
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Generation and characterization of NGLY1 patient-derived midbrain organoids.
Authors: Wei Et al.
Front Cell Dev Biol 2023;11:1039182
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Multidimensional analysis and therapeutic development using patient iPSC-derived disease models of Wolfram syndrome.
Authors: Mark J Et al.
JCI Insight 2022;7
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Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells.
Authors: Richard Et al.
Nat Genet 2022;54:1406-1416
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Classical Complement Pathway Inhibition in a Human-On-A-Chip" Model of Autoimmune Demyelinating Neuropathies."
Authors: Timothy Et al.
Adv Ther (Weinh) 2022;5
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An improved protocol for generation and characterization of human-induced pluripotent stem cell-derived retinal pigment epithelium cells.
Authors: Surendran Et al.
STAR Protoc 2022;3:101803
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Dynamic 3D Combinatorial Generation of hPSC-Derived Neuromesodermal Organoids With Diverse Regional and Cellular Identities.
Authors: Mustafa Et al.
Curr Protoc 2022;2:e568
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Derivation of nociceptive sensory neurons from hiPSCs with early patterning and temporally controlled NEUROG2 overexpression.
Authors: Emmanouil Et al.
Cell Rep Methods 2022;2:100341
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CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states.
Authors: Shinong Et al.
Nat Neurosci 2022;25:1528-1542
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Wnt-activating human skin organoid model of atopic dermatitis induced by Staphylococcus aureus and its protective effects by Cutibacterium acnes.
Authors: Kyung-Sun Et al.
iScience 2022;25:105150
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Uncovering specificity of endogenous TAU aggregation in a human iPSC-neuron TAU seeding model.
Authors: Jessica Et al.
iScience 2022;25:103658
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Selective activation and down-regulation of Trk receptors by neurotrophins in human neurons co-expressing TrkB and TrkC.
Authors: Jia Et al.
J Neurochem 2022;161:463-477
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A pendulum of induction between the epiblast and extra-embryonic endoderm supports post-implantation progression.
Authors: Jop Et al.
Development 2022;149
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Distinct properties of Ca2+ efflux from brain, heart and liver mitochondria: The effects of Na+, Li+ and the mitochondrial Na+/Ca2+ exchange inhibitor CGP37157.
Authors: Stefan Et al.
Cell Calcium 2021;96:102382
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Publicly Available hiPSC Lines with Extreme Polygenic Risk Scores for Modeling Schizophrenia.
Authors: Schahram Et al.
Complex Psychiatry 2021;6:68-82
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Resolving cell state in iPSC-derived human neural samples with multiplexed fluorescence imaging.
Authors: Beth A Et al.
Commun Biol 2021;4:786
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RSPO2 inhibits BMP signaling to promote self-renewal in acute myeloid leukemia.
Authors: Christof Et al.
Cell Rep 2021;36:109559
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Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids.
Authors: Ling Et al.
Cell Stem Cell 2021;28:1090-1104.e6
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Transplantable human motor networks as a neuron-directed strategy for spinal cord injury.
Authors: Philip J Et al.
iScience 2021;24:102827
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Human Pluripotent Stem Cells for High-Throughput Drug Screening and Characterization of Small Molecules.
Authors: Ruili Et al.
Methods Mol Biol 2021;2454:811-827
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In Vitro Generation of Posterior Motor Neurons from Human Pluripotent Stem Cells.
Authors: Anestis Et al.
Curr Protoc 2021;1:e244
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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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Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells.
Authors: Thomas S Et al.
Elife 2021;10
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Optogenetic Control of the BMP Signaling Pathway.
Authors: Steven Et al.
ACS Synth Biol 2020;9:3067-3078
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A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells.
Authors: Katja Et al.
Cell Stem Cell 2020;27:158-176.e10
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Generation of PAX7 Reporter Cells to Investigate Skeletal Myogenesis from Human Pluripotent Stem Cells.
Authors: April D Et al.
STAR Protoc 2020;1:100158
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Aberrant interaction of FUS with the U1 snRNA provides a molecular mechanism of FUS induced amyotrophic lateral sclerosis.
Authors: Frédéric H-T Et al.
Nat Commun 2020;11:6341
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Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons.
Authors: Bo Et al.
Mol Autism 2020;10:51
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Axon-seq for in Depth Analysis of the RNA Content of Neuronal Processes.
Authors: Eva Et al.
Bio Protoc 2019;9:e3312
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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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Generation of Induced Pluripotent Stem Cells from Patients with COL3A1 Mutations and Differentiation to Smooth Muscle Cells for ECM-Surfaceome Analyses.
Authors: Kenneth R Et al.
Methods Mol Biol 2017;1722:261-302
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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.