DMH-1 is a selective bone morphogenetic protein (BMP) type I receptor ALK2 inhibitor with an IC50 value of 108nM. DMH-1 blocks BMP receptor activation, thereby inhibiting Smad1/5/8 phosphorylation and downregulating Id1, Id2, and Id3 expression. DMH-1 suppresses BMP-mediated osteogenesis, mineralization, and cancer cell proliferation while promoting cardiomyocyte differentiation. DMH-1 can be used in studies related to tumors, stem cell and developmental biology, musculoskeletal and genetic diseases[1-4].
In vitro, treatment of A549 and H460 cells with 1-5μM DMH-1 for 24-72 hours decreased p-Smad1/5/8 levels and downregulated Id1, Id2, and Id3 mRNA expression. DMH-1 slowed cell migration, reduced cell proliferation, and increased the proportion of dead cells[5]. Treatment of A549 and H1299 cells with 1μM DMH-1 for 7-14 days reduced viable cell numbers, inhibited colony formation, and decreased soft agar anchorage-independent growth colonies[6]. Pretreatment of Hep3B cells with 10nM DMH-1 for 15-20 minutes followed by stimulation with 200ng/mL recombinant human BMP13 for 15 minutes to 24 hours blocked BMP13-induced SMAD1/5/9 phosphorylation, reduced ID1 mRNA expression, and inhibited cell proliferation[7].
In vivo, intraperitoneal injection of 5mg/kg DMH-1 every other day for 16 consecutive days to NSG mice bearing PC3-TxR cells reduced tumor volume and tumor weight and decreased Ki67-positive cell proportion in tumor tissue[8]. After intramuscular injection of Adex-cre and 1.5μg cardiotoxin into the hindlimb of caALK2fl/fl mice, intraperitoneal injection of 10mg/kg DMH-1 for 28 days. DMH-1 reduced the radiographic area of hindlimb heterotopic ossification[9]. Starting 3 days before left anterior descending coronary artery ligation surgery, intraperitoneal injection of 5mg/kg DMH-1 every other day to C57BL/6 mice until 28 days after surgery. DMH-1 decreased left ventricular ejection fraction and left ventricular fractional shortening, increased left ventricular end-diastolic diameter and left ventricular end-systolic diameter, and aggravated myocardial fibrosis area[10].
References:
[1] Hochgerner M, Jiang Y, Sun S, et al. Loss of ALK3 Ameliorates Acute but Aggravates Chronic Lung Inflammation In Vivo. Immunology. 2025 Oct;176(2):224-236.
[2] Zhang X, Miao Y, Li Z, et al. ACVR1 drives neuropathic pain by regulating NLRP3-Induced neuronal pyroptosis through the p38 and Smad1/5/8 pathways. Neuropharmacology. 2025 Aug 15;274:110469.
[3] Luo J, Wang Y, Chang HM, et al. ID3 mediates BMP2-induced downregulation of ICAM1 expression in human endometiral stromal cells and decidual cells. Front Cell Dev Biol. 2023 Feb 24;11:1090593.
[4] Zhang Y, Zhu H, Chang HM, et al. ALK3-SMAD1/5 Signaling Mediates the BMP2-Induced Decrease in PGE2 Production in Human Endometrial Stromal Cells and Decidual Stromal Cells. Front Cell Dev Biol. 2020 Sep 15;8:573028.
[5] Hao J, Lee R, Chang A, et al. DMH1, a Small Molecule Inhibitor of BMP Type I Receptors, Suppresses Growth and Invasion of Lung Cancer. PLoS ONE. 2014 Mar 6;9(3):e90748.
[6] Langenfeld E, Hong CC, Lanke G, et al. 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.
[7] Kersten V, Seitz T, Sommer J, et al. Bone Morphogenetic Protein 13 Has Protumorigenic Effects on Hepatocellular Carcinoma Cells In Vitro. Int J Mol Sci. 2023 Jul 4;24(13):11059.
[8] Xie C, Wang Z, Ba Y, et al. BMP signaling inhibition overcomes chemoresistance of prostate cancer. Am J Cancer Res. 2023;13(9):4073-4086.
[9] Pan H, Fleming N, Hong CC, et al. Methods for the reliable induction of heterotopic ossification in the conditional Alk2Q207D mouse. J Musculoskelet Neuronal Interact. 2020;20(1):149-159.
[10] Liu M, Pei J, Zeng C, et al. BMP7 attenuates myocardial injury and preserves cardiac function after myocardial infarction by inhibiting cardiomyocyte pyroptosis. Apoptosis. 2026;31:57.