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 Formula: C24H20N4O
Exact Mass: 380.16371
Molecular Weight: 380.44
Elemental Analysis: C, 75.77; H, 5.30; N, 14.73; O, 4.21
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
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
DMH-1 (0.5 μM) induces regulation of OCT4, Nanog, and PAX6 protein expression. DMH-1 significantly reduces the percentage of cells expressing the pluripotency marker proteins OCT4 and Nanog in both SM3 and CA6 cells. PAX6 expression is significantly up-regulated by day 5 and day 7 in CA6 and SM3 cells, respectively. DMH-1 induces regulation of pluripotency and neural precursor marker mRNAs. PAX6 can regulate the expression of SOX1 independently by manipulating the DMH-1 concentration during the neural induction of hiPSCs. DMH-1 (5 μM and 10 μM) inhibits CDDP-induced autophagy in HeLa cells and enhances the ability of CDDP to reduce HeLa cell viability, inhibits tamoxifen-induced autophagy in MCF-7 cells and enhances the ability of tamoxifen to reduce MCF-7 cell viability, inhibits 5-FU-induced autophagy in both MCF-7 and HeLa cells but does not affect the inhibitory effects of 5-FU on MCF-7 and HeLa cell viability. DMH-1 enhances the apoptotic induction effects of CDDP on HeLa cells after 24 h treatment. DMH-1 inhibits HeLa and MCF-7 cell proliferation. DMH-1 (20 μM) reduces the canonical phosphorylation of Smads 1,5 and 9. DMH-1 in combination with Cisplatin significantly decreases Ki-67 positive staining in the OVCAR8 cells. DMH-1 (20 µM) upregulates JAG1, reduces CYP1B1 and increases HAPLN1 expression in both OVCAR8 and NCI-RES cells.
DMH1 (5 mg/kg, i.p.) treatment significantly reduces the tumor growth in human lung cancer xenograft model.
- 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.
- 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.
- 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.
- 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.
- 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.
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