K02288 (1431985-92-0) Description:
K02288 is a selective and potent inhibitor of the bone morphogenetic protein (BMP) type I receptor kinases with IC50s in the range 1–2 nM against ALK1 and ALK2. K02288 has IC50 values of 1.1, 1.8, 6.4 nM for ALK2, ALK1 and ALK6 respectively and IC50s of 34.4, 302, 321 and 220 nM for other ALKs (3, 4, 5) and ActRIIA. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos.
K02288 is functionally similar to dorsomorphin, which is known to be the first small-molecule for BMP signaling inhibition.
BMP signalling is associated with many important physiological processes. It acts a central regulator of developmental processes such as organogenesis, gastrulation, mesoderm induction and endochondral bone formation. BMP signals are also related to diseases including pulmonary hypertension, juvenile polyposis syndrome, fibrodysplasia ossificans progressiva and hereditary hemorrhagic telangiectasia syndrome. BMP signaling inhibition might serve as a tool to study its role in other biological processes
Activation of bone morphogenetic protein (BMP) type I receptors, also known as activin receptor-like kinases (ALK1-7), leads to the assembly of SMAD complexes, which translocate to the nucleus to induce transcriptional activation important for normal development and tissue repair. K02288 is a 2-aminopyridine-based inhibitor of ALK1 and ALK2 with IC50 values of 1.8 and 1.1 nM, respectively.2 It is less selective for ALK3, 4, 5, and 6 subtypes and the type II BMP receptor ActRIIA, demonstrating IC50 values of 34.4, 302, 321, 6.4, and 220 nM, respectively. K02288 can prevent BMP4-induced SMAD1/5/8 pathway activation in vitro (IC50 = 100 nM) without affecting TGF-β signaling. Furthermore, at 8-10 µM, K02288 has been used to induce the dorsalization of zebrafish embryos. Through specific inhibition of BMP signaling, this compound can be used to research stem cell biology and disease models of musculoskeletal dysplasia and cancer.
K02288 (1431985-92-0) Specifications:
|Synonyms||K-02288; K 02288;|
|Molecular Weight||352.39 g/mol|
|Monoisotopic Mass||352.142 g/mol|
|Color||white to beige|
|Solubility||Soluble in DMSO (20 mg/ml), and ethanol (20 mg/ml).|
|Storage Temp.||0 – 4 C for short term (days to weeks), or -20 C for long term (months).|
|Shelf life||>2 years if stored properly|
|Handling||Protect from air and light|