DMH-1 [ALK2 Inhibitor]

Selective ALK2 inhibitor (IC50 = 108 nM). Prevent BMP signaling. When used in combination with SB 431542, It also promote human induced pluripotent stem cell (iPSC) neurogenesis. Show anti-tumor activity.

4-[6-[4-(1-Methylethoxy)phenyl]pyra zolo[1,5-a]pyrimidin-3-yl]-quinoline

Inhibitor

Neurological Disorders

DMH-1 (0.5 μM) induced the regulation of OCT4, Nanog and PAX6 protein expression. DMH-1 significantly reduced the percentage of cells expressing the pluripotency marker proteins OCT4 and Nanog in SM3 and CA6 cells. In CA6 and SM3 cells, PAX6 expression was significantly up-regulated on days 5 and 7, respectively. DMH-1 induces the modulation of pluripotency and neural precursor marker mRNA. PAX6 can independently regulate SOX1 expression by manipulating the concentration of DMH-1 during neural induction of hiPSCs [1]. DMH-1 (5μM and 10μM) inhibits CDDP-induced autophagy in HeLa cells, enhances CDDP's ability to reduce HeLa cell viability, inhibits tamoxifen-induced autophagy in MCF-7 cells, and enhances tamoxifen's ability to reduce MCF- ability. After 24 hours of treatment, DMH-1 enhanced the apoptosis induction effect of CDDP on HeLa cells. DMH-1 inhibits the proliferation of HeLa and MCF-7 cells [2]. DMH-1 (20 μM) reduced the typical phosphorylation of Smads 1, 5 and 9. The combination of DMH-1 and cisplatin significantly reduced Ki-67 positive staining of OVCAR8 cells. DMH-1 (20 µM) upregulates JAG1, reduces CYP1B1 and increases HAPLN1 expression in OVCAR8 and NCI-RES cells [3].

[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]. 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.

[3]. 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.

380.44

Powder

C24H20N4O

Synthetic

CC(C)OC(C=C3)=CC=C3C(C=N2)=CN1C2=C(C4=CC=NC5=C4C=CC=C5)C=N1

Soluble in DMSO (20mM)

IC50: 27 nM (ALK1), 107.9 nM (ALK2), <5 nM (ALK3), 47.6 nM (ALK6)

1206711-16-1

50997747

>98%

Store at +4°C

Room Temperature

For obtaining a higher solubility, please warm the tube at 37 °C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

For research use only