K02288

K02288 is a potent inhibitor of BMP signaling. K02288 has in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos.

Product information

CAS Number: 1431985-92-0

Molecular Weight: 352.38

Formula: C20H20N2O4

Chemical Name: 3-(6-amino-5-(3,4,5-trimethoxyphenyl)pyridin-3-yl)phenol

Smiles: COC1C(=CC(=CC=1OC)C1=CC(=CN=C1N)C1=CC(O)=CC=C1)OC

InChiKey: CJLMANFTWLNAKC-UHFFFAOYSA-N

InChi: InChI=1S/C20H20N2O4/c1-24-17-9-13(10-18(25-2)19(17)26-3)16-8-14(11-22-20(16)21)12-5-4-6-15(23)7-12/h4-11,23H,1-3H3,(H2,21,22)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

K02288 reduces a robust phosphorylation of Smad1/5/8 induced by BMP4 stimulation, with an apparent IC50 of 100 nM. K02288 causes near complete inhibition of Smad2 phosphorylation at 0.5 µM. K02288 binds to ALK1 in an ATP-mimetic fashion with two hydrogen bonds to the kinase hinge. K02288 also inhibits BMP9-ALK1 signalling, and induces a hypersprouting phenotype in HUVECs.

In Vivo:

K02288 (1 µM) induces dysfunctional angiogenesis in a chick embryo CAM model.

References:

1. Ono M, Toh H, Miyata T, Awaya T. Nucleotide sequence of the Syrian hamster intracisternal A-particle gene: close evolutionary relationship of type A particle gene to types B and D oncovirus genes. J Virol. 1985 Aug;55(2):387-94. PubMed PMID: 2991563; PubMed Central PMCID: PMC254945.
2. Sanvitale CE, Kerr G, Chaikuad A, Ramel MC, Mohedas AH, Reichert S, Wang Y, Triffitt JT, Cuny GD, Yu PB, Hill CS, Bullock AN. A new class of small molecule inhibitor of BMP signaling. PLoS One. 2013 Apr 30;8(4):e62721. doi: 10.1371/journal.pone.0062721. Print 2013. PubMed PMID: 23646137; PubMed Central PMCID: PMC3639963.
3. Mohedas A, Wang Y, Sanvitale CE, Canning P, Choi S, Xing X, Bullock AN, Cuny GD, Yu PB. Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J Med Chem. 2014 Aug 7. [Epub ahead of print] PubMed PMID: 25101911.

Products are for research use only. Not for human use.