SIS3 HCl

SIS3 HCl, a novel specific inhibitor of Smad3, inhibits TGF-β and activin signaling by suppressing Smad3 phosphorylation without affecting the MAPK/p38, ERK, or PI3-kinase signaling pathways.

Product information

CAS Number: 521984-48-5

Molecular Weight: 489.99

Formula: C28H28ClN3O3

Synonym:

(E)-SIS3

Chemical Name: (2E)-1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)-3-{1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl}prop-2-en-1-one hydrochloride

Smiles: Cl.CN1C(=C(/C=C/C(=O)N2CC3=CC(OC)=C(C=C3CC2)OC)C2=CC=CN=C12)C1C=CC=CC=1

InChiKey: CDKIEBFIMCSCBB-CALJPSDSSA-N

InChi: InChI=1S/C28H27N3O3.ClH/c1-30-27(19-8-5-4-6-9-19)22(23-10-7-14-29-28(23)30)11-12-26(32)31-15-13-20-16-24(33-2)25(34-3)17-21(20)18-31;/h4-12,14,16-17H,13,15,18H2,1-3H3;1H/b12-11+;

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO : ≥ 30 mg/mL (61.23 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: ≥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:

SIS3 HCl (0.3-10 μM; for 1 hour) attenuates the TGF-beta1-induced phosphorylation of Smad3 and interaction of Smad3 with Smad4. SIS3 HCl (0.1 , 10, 50 μM; 30 min) significantly suppresses the expression of FN and α-SMA, but not that of Sphk2 provoked by TGF-β1. SIS3 HCl (10 μM; 24 hours) significantly reduces both α-SMA and palladin expression that is enhanced by TWEAK in Primary human dermal fibroblasts. SIS3 HCl significantly inhibits L4 development at five concentrations from as low as 2 µM to 50 µM (5 µM, 10 µM, 20 µM and 50 µM) in a dose-dependent manner.

References:

1. Jinnin M et al. Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression. Mol Pharmacol. 2006 Feb;69(2):597-607.
2. Zhu X, et al. Sphingosine kinase 2 cooperating with Fyn promotes kidney fibroblast activation and fibrosis via STAT3 and AKT. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3824-3836.
3. Liu J, et al. Topical TWEAK Accelerates Healing of Experimental Burn Wounds in Mice. Front Pharmacol. 2018 Jun 21;9:660.
4. Li FF, et al. Identification and characterization of an R-Smad homologue (Hco-DAF-8) from Haemonchuscontortus. Parasit Vectors. 2020 Apr 3;13(1):164.

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