RepSox---TGF-β Type I Receptor ALK5 Inhibitor

RepSox (E-616452 or SJN 2511) is a highly potent, selective inhibitor of the TGF-β type I receptor ALK5 with IC50 of 23 nM and 4 nM for ATP binding to ALK5 and ALK5 autophosphorylation, respectively. It has good selectivity for ALK5 over a range of kinases, including p38 MAPK, JNK1 and GSK3 (IC50 > 16 μM). RepSox is able to successfully replace Sox2 in reprogramming by inhibiting transforming growth factor-β (Tgf-β) signaling, which in turn induces Nanog expression. Effect of RepSox inducing reprogramming does not require chromatin remodeling. RepSox is found to be efficient at generating iPSCs.

Product information

CAS Number: 446859-33-2

Molecular Weight: 287.32

Formula: C17H13N5

Chemical Name: 2-(5-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine

Smiles: CC1=CC=CC(=N1)C1NN=CC=1C1=CC=C2N=CC=CC2=N1

InChiKey: LBPKYPYHDKKRFS-UHFFFAOYSA-N

InChi: InChI=1S/C17H13N5/c1-11-4-2-5-16(20-11)17-12(10-19-22-17)13-7-8-14-15(21-13)6-3-9-18-14/h2-10H,1H3,(H,19,22)

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 100 mM

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: ≥360 days 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:

RepSox was used at 1-25 µM final concentration in vitro and in stem cell reprogramming.

In Vivo:

RepSox is able to be contribute to forming chimeric embryos in vivo when injected into blastocysts. A one-day treatment with RepSox is sufficient to replace transgenic Sox2.

References:

1. Gellibert F, et al. Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. (2004) J Med Chem. 47(18):4494-506.
2. Ichida JK, et al. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. (2009) Cell Stem Cell. 5(5):491-503.
3. Li W, et al. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. (2009) Cell Stem Cell. 4(1):16-9.
4. Liu X, et al. Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT-MET mechanism for optimal reprogramming. (2013) Nat Cell Biol. 15(7):829-38.
5. Hou P, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. (2013) Science. 341(6146):651-4.

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