Synonym
DMH2; DMH-2; DMH 2;
IUPAC/Chemical Name
4-(2-(4-(3-(Quinolin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)phenoxy)ethyl)morpholine
InChi Key
DXLXRNZCYAYUED-UHFFFAOYSA-N
InChi Code
InChI=1S/C27H25N5O2/c1-2-4-26-24(3-1)23(9-10-28-26)25-18-30-32-19-21(17-29-27(25)32)20-5-7-22(8-6-20)34-16-13-31-11-14-33-15-12-31/h1-10,17-19H,11-16H2
SMILES Code
N1(CCOC2=CC=C(C3=CN4C(N=C3)=C(C5=CC=NC6=CC=CC=C56)C=N4)C=C2)CCOCC1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.03.00
Biological target:
DMH2 is a potent BMP receptor antagonist.
In vitro activity:
Western blot analysis demonstrated that DMH2 caused a significant reduction in the expression of the BMP transcription factor pSmad 1/5 and its direct downstream targets Id1 and Id3 in Oct4/GFP, Nestin/GFP, and GFP (−) cells (Figure 6A). DMH2 caused significant growth inhibition of Oct4/GFP, Nestin/GFP, and GFP (−) cells (6B).
Reference: Mol Cancer. 2013 Oct 26;12(1):129. https://pubmed.ncbi.nlm.nih.gov/24160469/
In vivo activity:
This study next performed similar experiments using DMH2 (Fig. 3B). Mice receiving 0.5 mg/kg b.i.d. exhibited absolutely, but not significantly, higher hepatocyte proliferation at 48 hours compared with control animals. Mice receiving 1 mg/kg DMH2 demonstrated a trend toward increased hepatocyte proliferation, from 13.7 to 27.6% (P = 0.056). Mice receiving 2 mg/kg DMH2 demonstrated doubling of hepatocyte proliferation, 13.7 versus 26.9% (P = 0.027).
Reference: J Pharmacol Exp Ther. 2014 Dec;351(3):549-58. https://pubmed.ncbi.nlm.nih.gov/25271257/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
9.0 |
20.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
451.53
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 |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Langenfeld E, Deen M, Zachariah E, Langenfeld J. Small molecule antagonist of the bone morphogenetic protein type I receptors suppresses growth and expression of Id1 and Id3 in lung cancer cells expressing Oct4 or nestin. Mol Cancer. 2013 Oct 26;12(1):129. doi: 10.1186/1476-4598-12-129. PMID: 24160469; PMCID: PMC4176118.
2. Tsugawa D, Oya Y, Masuzaki R, Ray K, Engers DW, Dib M, Do N, Kuramitsu K, Ho K, Frist A, Yu PB, Bloch KD, Lindsley CW, Hopkins CR, Hong CC, Karp SJ. Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration. J Pharmacol Exp Ther. 2014 Dec;351(3):549-58. doi: 10.1124/jpet.114.216903. Epub 2014 Sep 30. PMID: 25271257; PMCID: PMC4244585.
In vitro protocol:
1. Langenfeld E, Deen M, Zachariah E, Langenfeld J. Small molecule antagonist of the bone morphogenetic protein type I receptors suppresses growth and expression of Id1 and Id3 in lung cancer cells expressing Oct4 or nestin. Mol Cancer. 2013 Oct 26;12(1):129. doi: 10.1186/1476-4598-12-129. PMID: 24160469; PMCID: PMC4176118.
In vivo protocol:
1. Tsugawa D, Oya Y, Masuzaki R, Ray K, Engers DW, Dib M, Do N, Kuramitsu K, Ho K, Frist A, Yu PB, Bloch KD, Lindsley CW, Hopkins CR, Hong CC, Karp SJ. Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration. J Pharmacol Exp Ther. 2014 Dec;351(3):549-58. doi: 10.1124/jpet.114.216903. Epub 2014 Sep 30. PMID: 25271257; PMCID: PMC4244585.
1: Newman JH, Augeri DJ, NeMoyer R, Malhotra J, Langenfeld E, Chesson CB, Dobias NS, Lee MJ, Tarabichi S, Jhawar SR, Bommareddy PK, Marshall S, Sadimin ET, Kerrigan JE, Goedken M, Minerowicz C, Jabbour SK, Li S, Carayannopolous MO, Zloza A, Langenfeld J. Novel bone morphogenetic protein receptor inhibitor JL5 suppresses tumor cell survival signaling and induces regression of human lung cancer. Oncogene. 2018 Apr 6. doi: 10.1038/s41388-018-0156-9. [Epub ahead of print] PubMed PMID: 29622797.
2: Tsugawa D, Oya Y, Masuzaki R, Ray K, Engers DW, Dib M, Do N, Kuramitsu K, Ho K, Frist A, Yu PB, Bloch KD, Lindsley CW, Hopkins CR, Hong CC, Karp SJ. Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration. J Pharmacol Exp Ther. 2014 Dec;351(3):549-58. doi: 10.1124/jpet.114.216903. Epub 2014 Sep 30. PubMed PMID: 25271257; PubMed Central PMCID: PMC4244585.
3: Langenfeld E, Deen M, Zachariah E, Langenfeld J. Small molecule antagonist of the bone morphogenetic protein type I receptors suppresses growth and expression of Id1 and Id3 in lung cancer cells expressing Oct4 or nestin. Mol Cancer. 2013 Oct 26;12(1):129. doi: 10.1186/1476-4598-12-129. PubMed PMID: 24160469; PubMed Central PMCID: PMC4176118.
4: Langenfeld E, Hong CC, Lanke G, Langenfeld J. Bone morphogenetic protein type I receptor antagonists decrease growth and induce cell death of lung cancer cell lines. PLoS One. 2013 Apr 12;8(4):e61256. doi: 10.1371/journal.pone.0061256. Print 2013. PubMed PMID: 23593444; PubMed Central PMCID: PMC3625205.
