DMH-1 is a potent and selective BMP inhibitor with IC₅₀s of 27/107.9/<5>

IC50: 27 nM (ALK1), 107.9 nM (ALK2), <5 nm (alk3), 47.6 (alk6)^[1]

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^[2]. 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^[3]. 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^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

DMH1 (5 mg/kg, i.p.) treatment significantly reduces the tumor growth in human lung cancer xenograft model^[5].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

380.44

C₂₄H₂₀N₄O

1206711-16-1

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 11.5 mg/mL (30.23 mM; Need ultrasonic and warming)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 1 mg/mL (2.63 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (2.63 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• [1]. Engers DW, et al. 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.

  [2]. Sheng Y, et al. 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.

  [3]. Neely MD, et al. DMH1, a highly selective small molecule BMP inhibitor promotes neurogenesis of hiPSCs: comparison of PAX6 and SOX1 expression during neural induction. ACS Chem Neurosci. 2012 Jun 20;3(6):482-91.

  [4]. Hover LD, et al. Small molecule inhibitor of the bone morphogenetic protein pathway DMH1 reduces ovarian cancer cell growth. Cancer Lett. 2015 Nov 1;368(1):79-87.

  [5]. Hao J, 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(6):e90748.

Cells are seeded in 96-well plates and treated with different drugs for appropriate time. Then 5 mg/mL MTT is added and incubated for 4 h at 37°C. Medium is then removed and 200 μL of DMSO is added to dissolve the crystal. Absorbance is measured at a wavelength of 490 nm with a plate reader.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Sub-confluent A549 cells are trypsinized and then suspended in serum free RPMI 1640 medium. The cell suspension (1×10⁶ cells in 100 µL medium for each injection) is injected subcutaneously into both the right and left flanks of eight-week old NOD SCID mice (n=5 for each group). Mice are given Intraperitoneal (i.p.) injection of the vehicle (12.5% 2-hydroxypropyl-β-cyclodextrin) or 5 mg/kg DMH1 every other day. The tumor sizes are measured with a vernier caliper from the sixth day to the fourth week after tumor implantation. The tumor volume (V) is calculated according to the formulation: Volume=(width)²×length/2. The tumor tissues are dissected at the end of study, and are sectioned and stained with H & E, and for immunohistochemical analysis.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Engers DW, et al. 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.

  [2]. Sheng Y, et al. 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.

  [3]. Neely MD, et al. DMH1, a highly selective small molecule BMP inhibitor promotes neurogenesis of hiPSCs: comparison of PAX6 and SOX1 expression during neural induction. ACS Chem Neurosci. 2012 Jun 20;3(6):482-91.

  [4]. Hover LD, et al. Small molecule inhibitor of the bone morphogenetic protein pathway DMH1 reduces ovarian cancer cell growth. Cancer Lett. 2015 Nov 1;368(1):79-87.

  [5]. Hao J, 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(6):e90748.