DMH-1
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MedKoo CAT#: 406555

CAS#: 1206711-16-1

Description: DMH-1 is a second-generation small molecule BMP inhibitor based on dorsomorphin. DMH-1 effectively inhibits the bone morphogenic protein (BMP) ALK2 receptor (IC50 = 108 nM). Treatment with DMH1 reduced lung metastasis and the tumors were less proliferative and more apoptotic. In the surrounding tumor microenvironment, treatment with DMH1 altered fibroblasts, lymphatic vessels and macrophages to be less tumor promoting. These results indicate that inhibition of BMP signaling may successfully target both the tumor and the surrounding microenvironment to reduce tumor burden and metastasis.

Chemical Structure

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DMH-1
CAS# 1206711-16-1
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406555
Name: DMH-1
CAS#: 1206711-16-1
Chemical Formula: C24H20N4O
Exact Mass: 380.16
Molecular Weight: 380.440
Elemental Analysis: C, 75.77; H, 5.30; N, 14.73; O, 4.21

Price and Availability

Size Price Availability Quantity
10mg USD 110 Ready to ship
25mg USD 200 Ready to ship
50mg USD 350 Ready to ship
100mg USD 600 Ready to ship
200mg USD 1050 Ready to ship
500mg USD 2150 Ready to ship
1g USD 3450 Ready to ship
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Synonym: DMH1; DMH 1; DMH-1

IUPAC/Chemical Name: 4-(6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline

InChi Key: JMIFGARJSWXZSH-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H20N4O/c1-16(2)29-19-9-7-17(8-10-19)18-13-26-24-22(14-27-28(24)15-18)20-11-12-25-23-6-4-3-5-21(20)23/h3-16H,1-2H3

SMILES Code: CC(OC1=CC=C(C2=CN3C(N=C2)=C(C4=CC=NC5=CC=CC=C45)C=N3)C=C1)C

Appearance: Solid powder

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, not in water

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

More Info:         

Biological target: DMH1 is a selective BMP receptor inhibitor with IC50 of 107.9 nM for ALK2, exhibiting no inhibition on AMPK, ALK5, KDR (VEGFR-2) or PDGFR.
In vitro activity: Since cell migration and invasion are known to play an important role in the progression of cancer metastasis, the effects of DMH1 on NSCLC cell migration and invasion were examined in vitro. The scratch-wound assay was used to determine NSCLC cell migration by creating wound gaps in the cultured A549 cells. Cells were then treated with DMSO or DMH1 for 24 hours respectively, and the gap distances were then normalized with the initially measured distances. As shown in Figure 2A and 2B, DMH1 dramatically slowed down migration in a dose-dependent manner. Similar effects of DMH1 on cell migration were also observed in another NSCLC cell line H460 (Figure 2C). In addition, the effect of DMH1 on cell invasion was examined by using modified Boyden chamber assay. A549 cells were seeded on matrigel-coated chambers, followed by 24-h incubation with or without DMH1. 3 µM DMH1 dramatically reduced A549 cell invasion through matrigel-coated membranes by about 52% in comparison with the vehicle controls (Figure 2D). Referenece: PLoS One. 2014 Mar 6;9(6):e90748. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24603907/
In vivo activity: The effect of DMH1 on lung tumor cell growth was examined in vivo. The A549 cells were subcutaneously inoculated in the two sides of lower rear flanks of Severe combined immunodeficiency (SCID) mice. Intraperitoneal (i.p.) injections of vehicle (12.5% 2-hydroxypropyl-β-cyclodextrin, n = 5) or 5 mg/kg DMH1 (n = 5) were initiated on the same day of tumor cell implantation and were performed every other day for 4 weeks. Tumor volumes were measured regularly starting on the sixth day after implantation. The tumor growth was fit into an exponential growth curve (Figure 4A) (R2  = 0.87 and 0.84 for the DMH1 treated and control mice, respectively). The result indicated that the rate for doubling tumor size in DMH1-treated mice was about one day longer than the controls (5.6 versus 4.7 days in the DMH1 treated and control mice, respectively) (Figure 4A). As the initial tumor volumes were similar, no statistical differences between the two groups were observed until day 25. At the end of 4-week treatment, DMH1 treatment resulted in a statistically significant reduction in tumor volumes by about 50% compared to the vehicle control group (p-value <0.05) (Figure 4B). The mouse body weights were measured every other day throughout the experiment, and no notable weight changes were observed in both the control and DMH1 treated groups, suggesting an absence of DMH1 toxic effect at the administered dose (data not shown). To further examine the effect of DMH1 on tumor cell proliferation in vivo, tumor tissue samples from both the vehicle control and DMH1 treatment groups were subjected to Hematoxylin and eosin-stained (H&E) and human specific Ki67 staining. H&E sections were examined for regions that contained tumor and stromal cells, and the result indicated both the vehicle and DMH1 treated groups consisted of a morphologically similar differentiated adenocarcinoma (data not shown). However, immunohistochemical study showed a conspicuously significant decrease of human proliferation marker Ki67 in the DMH1 treated versus vehicle groups, suggesting that DMH1 treatment may attenuate human A549 cancer cell proliferation in vivo (Figure 4C). Referenece: PLoS One. 2014 Mar 6;9(6):e90748. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24603907/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 11.5 30.23

Preparing Stock Solutions

The following data is based on the product molecular weight 380.44 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.

Recalculate based on batch purity %
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:
In vitro protocol: 1. Hao J, Lee R, Chang A, Fan J, Labib C, Parsa C, Orlando R, Andresen B, Huang Y. DMH1, a small molecule inhibitor of BMP type i receptors, suppresses growth and invasion of lung cancer. PLoS One. 2014 Mar 6;9(6):e90748. doi: 10.1371/journal.pone.0090748. PMID: 24603907; PMCID: PMC3946239. 2. Sheng Y, Sun B, Xie X, Li N, Dong D. DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline) inhibits chemotherapeutic drug-induced autophagy. Acta Pharm Sin B. 2015 Jul;5(4):330-6. doi: 10.1016/j.apsb.2014.12.010. Epub 2015 Feb 21. PMID: 26579463; PMCID: PMC4629267.
In vivo protocol: 1. Hao J, Lee R, Chang A, Fan J, Labib C, Parsa C, Orlando R, Andresen B, Huang Y. DMH1, a small molecule inhibitor of BMP type i receptors, suppresses growth and invasion of lung cancer. PLoS One. 2014 Mar 6;9(6):e90748. doi: 10.1371/journal.pone.0090748. PMID: 24603907; PMCID: PMC3946239.

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1: Owens P, Pickup MW, Novitskiy SV, Giltnane JM, Gorska AE, Hopkins CR, Hong CC, Moses HL. Inhibition of BMP signaling suppresses metastasis in mammary cancer. Oncogene. 2014 Jul 7. doi: 10.1038/onc.2014.189. [Epub ahead of print] PubMed PMID: 24998846.

2: Sheng Y, Sun B, Guo WT, Liu X, Wang YC, Xie X, Xiao XL, Li N, Dong DL. DMH1 (4-[6-(4-Isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline) is a novel autophagy inhibitor. Br J Pharmacol. 2014 Jun 19. doi: 10.1111/bph.12821. [Epub ahead of print] PubMed PMID: 24943256.

3: 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.

4: Hao J, Lee R, Chang A, Fan J, Labib C, Parsa C, Orlando R, Andresen B, Huang Y. DMH1, a small molecule inhibitor of BMP type i receptors, suppresses growth and invasion of lung cancer. PLoS One. 2014 Mar 6;9(6):e90748. doi: 10.1371/journal.pone.0090748. eCollection 2014. PubMed PMID: 24603907; PubMed Central PMCID: PMC3946239.

5: Matsumoto Y, Hayashi Y, Schlieve CR, Ikeya M, Kim H, Nguyen TD, Sami S, Baba S, Barruet E, Nasu A, Asaka I, Otsuka T, Yamanaka S, Conklin BR, Toguchida J, Hsiao EC. Induced pluripotent stem cells from patients with human fibrodysplasia ossificans progressiva show increased mineralization and cartilage formation. Orphanet J Rare Dis. 2013 Dec 9;8:190. doi: 10.1186/1750-1172-8-190. PubMed PMID: 24321451; PubMed Central PMCID: PMC3892046.

6: Chang HM, Cheng JC, Klausen C, Leung PC. BMP15 suppresses progesterone production by down-regulating StAR via ALK3 in human granulosa cells. Mol Endocrinol. 2013 Dec;27(12):2093-104. doi: 10.1210/me.2013-1233. Epub 2013 Oct 18. PubMed PMID: 24140593.

7: Sun B, Sheng Y, Huo R, Hu CW, Lu J, Li SL, Liu X, Wang YC, Dong DL. Bone morphogenetic protein-4 contributes to the down-regulation of Kv4.3 K+ channels in pathological cardiac hypertrophy. Biochem Biophys Res Commun. 2013 Jul 12;436(4):591-4. doi: 10.1016/j.bbrc.2013.05.113. Epub 2013 Jun 6. PubMed PMID: 23747723.

8: Engers DW, Frist AY, Lindsley CW, Hong CC, Hopkins CR. Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52. doi: 10.1016/j.bmcl.2013.03.113. Epub 2013 Apr 11. PubMed PMID: 23639540; PubMed Central PMCID: PMC3677712.

9: Sun B, Huo R, Sheng Y, Li Y, Xie X, Chen C, Liu HB, Li N, Li CB, Guo WT, Zhu JX, Yang BF, Dong DL. Bone morphogenetic protein-4 mediates cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy. Hypertension. 2013 Feb;61(2):352-60. doi: 10.1161/HYPERTENSIONAHA.111.00562. Epub 2012 Dec 17. PubMed PMID: 23248151.

10: Chouinard-Pelletier G, Jahnsen ED, Jones EA. Increased shear stress inhibits angiogenesis in veins and not arteries during vascular development. Angiogenesis. 2013 Jan;16(1):71-83. doi: 10.1007/s10456-012-9300-2. Epub 2012 Sep 2. PubMed PMID: 22941228.