521984-48-5 Usage
Uses
Sugar insensitive 3 (SIS3) has been used as smad3?inhibitor in various cells.
Biological Activity
sis3 is an inhibitor of smad3.the receptor-associated smads, such as smad2 and smad3, directly interact with activated tgf-receptor type i. smads form heteromeric complexes with smad4, which is a common mediator for all smad pathways.
Biochem/physiol Actions
Sugar insensitive 3 (SIS3) promotes drug-induced apoptosis and hinders the function of adenosine triphosphate (ATP)-binding cassette (ABC) transporter (ABCB1) and ABCG2. It resensitizes ABCB1 and ABCG2 overexpressed in cancerous cells, which contributes to chemotherapeutics.
in vitro
in the reporter assay, it was found that the increased luciferase activity of p3tp-lux could be abrogated by the sis3 treatment in a dosedependent manner. immunoprecipitation revealed sis3 attenuated the tgf-1-induced phosphorylation of smad3 and interaction of smad3 with smad4. whereas, sis3 did not affect the phosphorylation of smad2. in addition, it was found that sis3 attenuated the effects of tgf-1 by reducing the transcriptional activity. sis3 could also inhibit the myofibroblast differentiation of fibroblasts by tgf-1. moreover, sis3 diminished the constitutive phosphorylation of smad3 completely [1].
in vivo
animal study showed that, in tie2-cre;loxp-egfp mice, ages could induce endomt. immunoprecipitation and western blotting showed that smad3 could be activated by ages but was inhibited by sis3 in both mmecs and in stz-induced diabetic nephropathy. furthermore, confocal microscopy and real-time pcr showed that sis3 could abrogate endomt, reduce renal fibrosis, as well as retard nephropathy progression [2].
IC 50
3 μm
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] li j et al. blockade of endothelial-mesenchymal transition by a smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. diabetes.2010 oct;59(10):2612-24.
Check Digit Verification of cas no
The CAS Registry Mumber 521984-48-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 5,2,1,9,8 and 4 respectively; the second part has 2 digits, 4 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 521984-48:
(8*5)+(7*2)+(6*1)+(5*9)+(4*8)+(3*4)+(2*4)+(1*8)=165
165 % 10 = 5
So 521984-48-5 is a valid CAS Registry Number.
InChI:InChI=1/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+;
521984-48-5Relevant articles and documents
AMIDE DERIVATIVES AND DRUGS
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Page 48, (2010/02/08)
The present invention provides an amide derivative represented by the following formula [1]: wherein n represents 0 or 1; X represents CR4 or N; Y represents CR6 or N; Z represents CR7 or N; R1 and R2 may be the same or different and each represents hydrogen, optionally substituted alkyl, acyl, optionally substituted aryl, or an optionally substituted aromatic heterocyclic group; R4, R5, R6 and R7 may be the same or different and each represents hydrogen, halogen, hydroxy, amino, alkyl, haloalkyl, alkoxy, monoalkylamino, dialkylamino, arylalkyl, cyano, or nitro; and R3 represents optionally substituted alkylamino, optionally substituted arylamino, or optionally substituted cyclic amino, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising them as an active ingredient. The compound of the present invention is useful as a TGF-β inhibitor.
