1432597-26-6

Basic information

• Product Name: LDN212854
• Synonyms: LDN212854;5-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyriMidin-3-yl]quinoline;Quinoline, 5-[6-[4-(1-piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-;BMP Inhibitor III;5-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline LDN 212854;LDN 212854 5-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline;LDN-212854, >=98%
• CAS NO: 1432597-26-6
• Molecular Formula: C₂₅H₂₂N₆
• Molecular Weight: 406.48238
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 1432597-26-6.mol

Chemical Properties

• Appearance: white to beige/
• Density: 1.33±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble1mg/mL, clear (warmed)
• PKA: 8.79±0.10(Predicted)
• CAS DataBase Reference: LDN212854(CAS DataBase Reference)
• NIST Chemistry Reference: LDN212854(1432597-26-6)
• EPA Substance Registry System: LDN212854(1432597-26-6)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 1432597-26-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
LDN212854 is used as a selective BMP receptor inhibitor for targeting the ALK2 receptor with high potency and selectivity. Its application in this industry is primarily focused on the development of novel therapeutic strategies for various diseases, including those related to the dysregulation of BMP signaling pathways.
Used in COVID-19 Research:
LDN212854 is used as a research tool in the context of COVID-19, where it may help in understanding the role of BMP signaling in the disease's progression and potentially contribute to the development of new treatment options.
Used in Cancer Research:
Although not explicitly mentioned in the provided materials, the potent and selective nature of LDN212854 could potentially make it a candidate for cancer research, where it may be investigated for its effects on tumor growth and progression through the modulation of BMP signaling pathways.
Used in Drug Development:
LDN212854 is used as a starting point for the development of new drugs targeting the BMP receptor family. Its high selectivity and potency make it a valuable compound for designing and optimizing novel therapeutic agents with improved efficacy and reduced side effects.
Used in Cellular and Molecular Biology Research:
LDN212854 can be employed as a research tool in cellular and molecular biology to study the role of BMP receptors in various cellular processes, such as cell differentiation, proliferation, and apoptosis. This can help in understanding the underlying mechanisms of diseases and pave the way for the development of targeted therapies.

In vitro

In myofibroblast C2C12 cells, LDN-212854 exhibits greater selectivity for BMP6-versus BMP4-induced osteogenic differentiation.

In vivo

LDN-212854 (6 mg/kg, i.p.) effectively neutralize ALK2 signaling in vivo, and potently inhibits heterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva.

Biological Activity

ldn-212854 is a selective inhibitor of bone morphogenetic protein (bmp) signaling with ic50 value of 1.2nm [1].in the kinase assay, ldn-212854 shows inhibitory activities against caalk2 and caalk5 with ic50 values of 16nm and 2μm, respectively. it demonstrates that ldn-212854 is selective against bmp over tgf-β signaling. besides that, the inhibition of caalk2 caused by ldn-212854 is 6- and 10-fold more potent than that of caalk1 and caalk3, respectively. in c2c12 cells transfected with bmp receptors, ldn-212854 also exerts preferential inhibition against caalk2. furthermore, in a transgenic alk2q207d model of heterotopic ossification, treatment of ldn-212854 prevents the formation of heterotopic bone and preserves limb range of motion [1].

Biochem/physiol Actions

LDN-212854 is also known as 5-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline. LDN-212854 prevents heterotopic ossification in an inducible mutant ALK2 (activin receptor-like kinase 2).

references

[1] mohedas a h, xing x, armstrong k a, et al. development of an alk2-biased bmp type i receptor kinase inhibitor. acs chemical biology, 2013, 8(6): 1291-1302.

Upstream product

• 1062368-25-5 C₂₁H₂₅N₅O₂ 
• 705263-10-1 6-bromo-pyrazolo[1,5-α]pyrimidine 
• 1435614-98-4 C₁₆H₁₇N₅ 
• 1435615-10-3 C₁₆H₁₆IN₅ 
• 355386-94-6 quinolin-5-ylboronic acid 

Relevant articles and documents

A synthetic bone morphogenetic protein receptor inhibitors

The invention discloses a method for synthesizing a bone morphogenetic protein receptor inhibitor, and solves the problem of long inhibitor synthesis route in the prior art. The method comprises the following steps: 1, obtaining an intermediate represented by formula (III) shown in the specification, wherein R1 in the formula (III) can be a first formula or a second formula also shown in the specification; 2, adding 5-bromoquinoline to the intermediate represented by formula (III), adding potassium acetate and palladium acetate, adding N,N-dimethyl acetamide, reacting, and cooling to room temperature; and 3, adding water to precipitate a solid when the R1 is the first formula, drying, and separating to obtain a product 1; and extracting the above obtained reaction solution by ethyl acetate when the R1 is the second formula, drying the obtained organic phase to remove a solvent, separating to obtain the product 1, dissolving the product 1 in methanol, adding concentrated hydrochloric acid, reacting to precipitate a solid, carrying out pumping filtration, washing, and drying to obtain a product 2. The method has the advantages of short preparation steps, low price of adopted raw materials, and high yield of target products.

BMP INHIBITORS AND METHODS OF USE THEREOF

The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

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

A structure-activity relationship of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 versus ALK3. The potency contributions of several 3-position substituents were evaluated with subtle structural changes leading to significant changes in potency. From these studies, a novel 5-quinoline molecule was identified and designated an MLPCN probe molecule, ML347, which shows >300-fold selectivity for ALK2 and presents the community with a selective molecular probe for further biological evaluation.