DMH1

Activin/Nodal/TGFβ pathway inhibitor; Inhibits ALK2

DMH1

Activin/Nodal/TGFβ pathway inhibitor; Inhibits ALK2

From: 66 USD
Catalog #
73632_C
Activin/Nodal/TGFβ pathway inhibitor; Inhibits ALK2

Overview

DMH1 (dorsomorphin homolog 1) is a selective inhibitor of activin receptor-like kinase 2 (ALK2; IC₅₀ = 13 - 108 nM), a type I bone morphogenetic protein (BMP) receptor (Hao et al.; Mohedas et al.). DMH1 exhibits no detectable inhibition of ALK4, ALK5, AMPK, KDR (VEGFR2), or PDGFRβ, although it inhibits ALK1 and ALK3 at nanomolar concentrations (Hao et al.; Mohedas et al.).

DIFFERENTIATION
· Induces differentiation of mouse embryonic stem cells to cardiomyocyte progenitor cells (Ao et al.).
· Induces differentiation of human induced pluripotent stem cells to SOX1 and PAX6 expressing neural precursor cells (Neely et al.).
· Dorsalizes the embryonic axis without disrupting the angiogenic process in early zebrafish embryos (Hao et al. 2010).

CANCER RESEARCH
· Suppresses non-small cell lung cancer cell growth, migration and invasion in vitro, and attenuates xenografted lung tumor growth in vivo (Hao et al. 2014).
· Inhibits chemotherapeutic drug-induced autophagy response (Sheng et al.).
Alternative Names
Dorsomorphin homolog 1
Cell Type
Cancer Cells and Cell Lines, Cardiomyocytes, PSC-Derived, Neural Cells, PSC-Derived, Neural Stem and Progenitor Cells, Pluripotent Stem Cells
Species
Human, Mouse, Rat, Non-Human Primate, Other
Application
Differentiation
Area of Interest
Cancer, Stem Cell Biology
CAS Number
1206711-16-1
Chemical Formula
C₂₄H₂₀N₄O
Molecular Weight
380.4 g/mol
Purity
≥ 98%
Pathway
Activin/Nodal/TGFβ
Target
ALK2

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
DMH1
Catalog #
73632, 73634
Lot #
All
Language
English
Product Name
DMH1
Catalog #
73632, 73634, 100-1043
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
DMH1
Catalog #
73632, 73634
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
DMH1
Catalog #
100-1043
Lot #
All
Language
English

Applications

This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Resources and Publications

Publications (7)

DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline) inhibits chemotherapeutic drug-induced autophagy. Sheng Y et al. Acta pharmaceutica Sinica. B 2015 JUL

Abstract

Our previous work found that DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl]quinoline) was a novel autophagy inhibitor. Here, we aimed to investigate the effects of DMH1 on chemotherapeutic drug-induced autophagy as well as the efficacy of chemotherapeutic drugs in different cancer cells. We found that DMH1 inhibited tamoxifen- and cispcis-diaminedichloroplatinum (II) (CDDP)-induced autophagy responses in MCF-7 and HeLa cells, and potentiated the anti-tumor activity of tamoxifen and CDDP for both cells. DMH1 inhibited 5-fluorouracil (5-FU)-induced autophagy responses in MCF-7 and HeLa cells, but did not affect the anti-tumor activity of 5-FU for these two cell lines. DMH1 itself did not induce cell death in MCF-7 and HeLa cells, but inhibited the proliferation of these cells. In conclusion, DMH1 inhibits chemotherapeutic drug-induced autophagy response and the enhancement of efficacy of chemotherapeutic drugs by DMH1 is dependent on the cell sensitivity to drugs.
DMH1, a small molecule inhibitor of BMP type i receptors, suppresses growth and invasion of lung cancer. Hao J et al. PloS one 2014 JAN

Abstract

The bone morphogenetic protein (BMP) signaling cascade is aberrantly activated in human non-small cell lung cancer (NSCLC) but not in normal lung epithelial cells, suggesting that blocking BMP signaling may be an effective therapeutic approach for lung cancer. Previous studies demonstrated that some BMP antagonists, which bind to extracellular BMP ligands and prevent their association with BMP receptors, dramatically reduced lung tumor growth. However, clinical application of protein-based BMP antagonists is limited by short half-lives, poor intra-tumor delivery as well as resistance caused by potential gain-of-function mutations in the downstream of the BMP pathway. Small molecule BMP inhibitors which target the intracellular BMP cascades would be ideal for anticancer drug development. In a zebrafish embryo-based structure and activity study, we previously identified a group of highly selective small molecule inhibitors specifically antagonizing the intracellular kinase domain of BMP type I receptors. In the present study, we demonstrated that DMH1, one of such inhibitors, potently reduced lung cell proliferation, promoted cell death, and decreased cell migration and invasion in NSCLC cells by blocking BMP signaling, as indicated by suppression of Smad 1/5/8 phosphorylation and gene expression of Id1, Id2 and Id3. Additionally, DMH1 treatment significantly reduced the tumor growth in human lung cancer xenograft model. In conclusion, our study indicates that small molecule inhibitors of BMP type I receptors may offer a promising novel strategy for lung cancer treatment.
Development of an ALK2-biased BMP type I receptor kinase inhibitor. Mohedas AH et al. ACS chemical biology 2013 JAN

Abstract

The bone morphogenetic protein (BMP) signaling pathway has essential functions in development, homeostasis, and the normal and pathophysiologic remodeling of tissues. Small molecule inhibitors of the BMP receptor kinase family have been useful for probing physiologic functions of BMP signaling in vitro and in vivo and may have roles in the treatment of BMP-mediated diseases. Here we describe the development of a selective and potent inhibitor of the BMP type I receptor kinases, LDN-212854, which in contrast to previously described BMP receptor kinase inhibitors exhibits nearly 4 orders of selectivity for BMP versus the closely related TGF-β and Activin type I receptors. In vitro, LDN-212854 exhibits some selectivity for ALK2 in preference to other BMP type I receptors, ALK1 and ALK3, which may permit the interrogation of ALK2-mediated signaling, transcriptional activity, and function. LDN-212854 potently inhibits heterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva. These findings represent a significant step toward developing selective inhibitors targeting individual members of the highly homologous BMP type I receptor family. Such inhibitors would provide greater resolution as probes of physiologic function and improved selectivity against therapeutic targets.

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