Synonym
DMH4; DMH 4; DMH-4;
IUPAC/Chemical Name
6-[4-[2-(4-Morpholinyl)ethoxy]phenyl]-3-phenylpyrazolo[1,5-a]pyrimidine
InChi Key
SKZQZGSPYYHTQG-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H24N4O2/c1-2-4-20(5-3-1)23-17-26-28-18-21(16-25-24(23)28)19-6-8-22(9-7-19)30-15-12-27-10-13-29-14-11-27/h1-9,16-18H,10-15H2
SMILES Code
C12=C(C3=CC=CC=C3)C=NN1C=C(C4=CC=C(OCCN5CCOCC5)C=C4)C=N2
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
>2 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
2934.99.9001
Biological target:
DMH4 is a potent and selective inhibitor of VEGFR2 with an IC50 of 0.16 µM.
In vitro activity:
Moreover, blockade of VEGF receptor-2 (VEGFR-2), which is the primary receptor for VEGF, with the pharmacological inhibitor DMH4, or with specific VEGFR-2 siRNA, substantially inhibited C1P-stimulated cell growth.
Reference: Exp Cell Res. 2017 Dec 15;361(2):277-283. https://pubmed.ncbi.nlm.nih.gov/29080796/
In vivo activity:
In the above in vivo zebrafish SAR (structure activity relationship) study, DMH4 had no discernable effect on DV (dorsoventral) (Figure 5b), but caused significant defects in the ISV (intersomitic vessel) and SIV (subintestinal vessel) formation (Figure 5a). Additionally, 1 μM DMH4 effectively blocked angiogenesis in a Matrigel angiogenesis assay using human umbilical vein endothelial cells (Figure 5c).
Reference: ACS Chem Biol. 2010 Feb 19;5(2):245-53. https://pubmed.ncbi.nlm.nih.gov/20020776/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
400.48
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. Ouro A, Arana L, Riazy M, Zhang P, Gomez-Larrauri A, Steinbrecher U, Duronio V, Gomez-Muñoz A. Vascular endothelial growth factor mediates ceramide 1-phosphate-stimulated macrophage proliferation. Exp Cell Res. 2017 Dec 15;361(2):277-283. doi: 10.1016/j.yexcr.2017.10.027. Epub 2017 Oct 31. PMID: 29080796.
2. Ramírez-Rodríguez GB, Perera-Murcia GR, Ortiz-López L, Vega-Rivera NM, Babu H, García-Anaya M, González-Olvera JJ. Vascular endothelial growth factor influences migration and focal adhesions, but not proliferation or viability, of human neural stem/progenitor cells derived from olfactory epithelium. Neurochem Int. 2017 Sep;108:417-425. doi: 10.1016/j.neuint.2017.06.001. Epub 2017 Jun 7. PMID: 28600187.
3. Hao J, Ho JN, Lewis JA, Karim KA, Daniels RN, Gentry PR, Hopkins CR, Lindsley CW, Hong CC. In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS Chem Biol. 2010 Feb 19;5(2):245-53. doi: 10.1021/cb9002865. PMID: 20020776; PMCID: PMC2825290.
In vitro protocol:
1. Ouro A, Arana L, Riazy M, Zhang P, Gomez-Larrauri A, Steinbrecher U, Duronio V, Gomez-Muñoz A. Vascular endothelial growth factor mediates ceramide 1-phosphate-stimulated macrophage proliferation. Exp Cell Res. 2017 Dec 15;361(2):277-283. doi: 10.1016/j.yexcr.2017.10.027. Epub 2017 Oct 31. PMID: 29080796.
2. Ramírez-Rodríguez GB, Perera-Murcia GR, Ortiz-López L, Vega-Rivera NM, Babu H, García-Anaya M, González-Olvera JJ. Vascular endothelial growth factor influences migration and focal adhesions, but not proliferation or viability, of human neural stem/progenitor cells derived from olfactory epithelium. Neurochem Int. 2017 Sep;108:417-425. doi: 10.1016/j.neuint.2017.06.001. Epub 2017 Jun 7. PMID: 28600187.
In vivo protocol:
1. Hao J, Ho JN, Lewis JA, Karim KA, Daniels RN, Gentry PR, Hopkins CR, Lindsley CW, Hong CC. In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS Chem Biol. 2010 Feb 19;5(2):245-53. doi: 10.1021/cb9002865. PMID: 20020776; PMCID: PMC2825290.
1: Ouro A, Arana L, Riazy M, Zhang P, Gomez-Larrauri A, Steinbrecher U, Duronio V, Gomez-Muñoz A. Vascular endothelial growth factor mediates ceramide 1-phosphate-stimulated macrophage proliferation. Exp Cell Res. 2017 Dec 15;361(2):277-283. doi: 10.1016/j.yexcr.2017.10.027. Epub 2017 Oct 31. PubMed PMID: 29080796.
2: Ramírez-Rodríguez GB, Perera-Murcia GR, Ortiz-López L, Vega-Rivera NM, Babu H, García-Anaya M, González-Olvera JJ. Vascular endothelial growth factor influences migration and focal adhesions, but not proliferation or viability, of human neural stem/progenitor cells derived from olfactory epithelium. Neurochem Int. 2017 Sep;108:417-425. doi: 10.1016/j.neuint.2017.06.001. Epub 2017 Jun 7. PubMed PMID: 28600187.
3: Saryeddine L, Zibara K, Kassem N, Badran B, El-Zein N. EGF-Induced VEGF Exerts a PI3K-Dependent Positive Feedback on ERK and AKT through VEGFR2 in Hematological In Vitro Models. PLoS One. 2016 Nov 2;11(11):e0165876. doi: 10.1371/journal.pone.0165876. eCollection 2016. PubMed PMID: 27806094; PubMed Central PMCID: PMC5091849.
4: Huang S, Tang Y, Peng X, Cai X, Wa Q, Ren D, Li Q, Luo J, Li L, Zou X, Huang S. Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs. Oncol Rep. 2016 Oct;36(4):2025-32. doi: 10.3892/or.2016.4997. Epub 2016 Aug 2. PubMed PMID: 27498716.
5: Shi L, Ko S, Ko ML, Kim AJ, Ko GY. Peptide Lv augments L-type voltage-gated calcium channels through vascular endothelial growth factor receptor 2 (VEGFR2) signaling. Biochim Biophys Acta. 2015 May;1853(5):1154-64. doi: 10.1016/j.bbamcr.2015.02.007. Epub 2015 Feb 17. PubMed PMID: 25698653; PubMed Central PMCID: PMC4382007.
6: Fotinos A, Nagarajan N, Martins AS, Fritz DT, Garsetti D, Lee AT, Hong CC, Rogers MB. Bone morphogenetic protein-focused strategies to induce cytotoxicity in lung cancer cells. Anticancer Res. 2014 May;34(5):2095-104. PubMed PMID: 24778011; PubMed Central PMCID: PMC4791537.
7: Lee MC, Toh LL, Yaw LP, Luo Y. Drosophila octamer elements and Pdm-1 dictate the coordinated transcription of core histone genes. J Biol Chem. 2010 Mar 19;285(12):9041-53. doi: 10.1074/jbc.M109.075358. Epub 2010 Jan 22. PubMed PMID: 20097756; PubMed Central PMCID: PMC2838325.
