ALK5 Inhibitor II CAS 446859-33-2

ALK5 INHIBITOR I Introduction

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ALK5 Inhibitor II is a potent and selective small molecule inhibitor of TGF-β type 1 receptor. It appears as a yellow solid, slightly pale yellow. CAS: 446859-33-2; Molecular formula: C17H13N5; Molecular weight: 287.32.
ALK5 INHIBITOR I was first reported by Gellibert, F. et al. in 2004 in the "Journal of Medicinal Chemistry" as a new series of 1,5-naphthyridine derivatives. Subsequently, it was produced and sold by several biochemical reagent suppliers. It is mainly applied in
stem cell and reprogramming research, cell differentiation, cell behavior research, and adipogenesis.

What is the mechanism of action of ALK5 INHIBITOR I?

ALK5 inhibitor II, also known as RepSox, is an ATP-competitive small molecule inhibitor with highly selective target. It can bind to the ATP binding region of the TGF-β type I receptor ALK5, thereby inhibiting the autophosphorylation of ALK5. The obtained IC50 value is only 4 nM, indicating a strong inhibitory effect. 
After the ALK5 activity is suppressed, the downstream Smad2/3 proteins cannot complete the phosphorylation activation step. The activated Smad2/3 cannot assemble with Smad4 to form a complex protein and cannot be transported into the cell nucleus. The entire TGF-β signaling pathway is thus interrupted, and the transcription process of downstream genes regulated by this pathway cannot be normally initiated.
The researchers also tested 9 other kinases such as p38 MAPK and GSK3. The IC50 values of this inhibitor for all of them exceeded 16 μM, which clearly indicates that E-616452 does not interfere with the physiological functions of these kinases and demonstrates excellent target specificity.

What is the use of ALK5 INHIBITOR I?

E-616452 is a commonly used small molecule product in life science experiments. In actual experimental scenarios, there are mainly three practical research directions:
When conducting stem cell induction and cell reprogramming experiments, this product has high recognition value. The most classic usage is to not add the Sox2 transcription factor separately. By blocking the TGF-β signaling pathway and upregulating the expression level of the Nanog gene, it can significantly improve the reprogramming success rate of iPS cells. When culturing human pluripotent stem cells on a daily basis, it is also often directly added to the basic culture medium for use.
Secondly, it is frequently used in topics related to cell directed differentiation and tissue repair and regeneration. Using ALK5 Inhibitor II can make adipose stem cells differentiate into Schwann cell-like cells, which can provide support and repair effects for damaged peripheral nerves and is often used in model studies related to nerve injury repair.
It can also regulate the differentiation process of retinal pigment epithelial cells and brown adipose precursor cells, and conduct mechanism research on obesity and type 2 diabetes.

MF of ALK5 INHIBITOR I

CAS	446859-33-2
Molecular formula	C17H13N5
Molecular weight	287.32
Melting point	501.9±50.0 °C
Density	1.296±0.06 g/cm3
Boiling point	421.13°C

Specification

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FAQ: 

Q1:What other applications does E-616452 have besides stem cell reprogramming?
Used for research on nerve regeneration and the study of osteoclast differentiation in osteoporosis.
Q2: What is the mechanism and selectivity of E-616452?
It exhibits extremely high selectivity for ALK5 and shows very weak inhibitory activity against nine other kinases, such as p38 MAPK and GSK3.
Q3:Can E-616452 be used directly to treat cancer or fibrotic diseases?

No. This product is currently only a prototype for research and development purposes; it is not an approved clinical product.

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