SIS3

• Description:

  SIS3 is a potent and selective inhibitor of Smad3 with an IC50 of 3 μM for Smad3 phosphorylation. SIS3 inhibits the myofibroblast differentiation of fibroblasts by TGF-β1[1].

• UNSPSC:

  12352005

• Hazard Statement:

  H302, H315, H319, H335

• Target:

  TGF-beta/Smad

• Type:

  Reference compound

• Related Pathways:

  Stem Cell/Wnt; TGF-beta/Smad

• Applications:

  Cancer-Kinase/protease

• Field of Research:

  Inflammation/Immunology

• Assay Protocol:

  https://www.medchemexpress.com/sis3.html

• Concentration:

  10mM

• Purity:

  99.62

• Solubility:

  DMSO : 100 mg/mL (ultrasonic) |H2O : < 0.1 mg/mL (ultrasonic; warming; heat to 60°C)

• Smiles:

  [H]Cl.O=C (/C=C/C1=C (N (C2=NC=CC=C21) C) C3=CC=CC=C3) N4CC5=C (CC4) C=C (C (OC) =C5) OC

• Molecular Formula:

  C28H28ClN3O3

• Molecular Weight:

  489.99

• Precautions:

  H302, H315, H319, H335

• References & Citations:

  [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.|[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.

• Shipping Conditions:

  Room Temperature

• Storage Conditions:

  4°C (Powder, sealed storage, away from moisture)

• Scientific Category:

  Reference compound1

• Clinical Information:

  No Development Reported

• Citation 01:

  Acta Histochem. 2023 Feb;125 (2) :152010.|Am J Physiol Cell Physiol. 2022 Jul 1;323 (1) :C133-C144.|Am J Physiol Renal Physiol. 2023 May 1;324 (5) :F433-F445.|Am J Reprod Immunol. 2021 Mar;85 (3) :e13344.|Am J Transl Res. 2020 Feb 15;12 (2) :478-492.|Am J Transl Res. 2021 Sep 15;13 (9) :10908-10921.|Antioxidants (Basel) . 2022 Dec 15;11 (12) :2469.|Aquaculture. 15 September 2022, 738360.|Bioact Mater. 2025 Oct 15:56:77-94.|Biochem Pharmacol. 2022 Jan:195:114846.|Biochem Pharmacol. 2023 Oct:216:115796.|Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864 (11) :3824-3836.|Biochim Biophys Acta Mol Cell Res. 2022 May 13;1869 (9) :119285.|Biol Reprod. 2025 Aug 7:ioaf179.|Biomed Pharmacother. 2023 Mar:159:114216.|Biomed Pharmacother. 2023 Sep:165:115225.|Biomed Pharmacother. 2025 May 1:187:118094.|bioRxiv. 2025 Jun 24.|bioRxiv. 2025 May 05.|BMC Med. 2021 Oct 15;19 (1) :247.|Brain Behav Immun. 2021 Jul:95:154-167.|Brain Res. 2022 Jan 15:1775:147711.|Cancer Cell Int. 2024 Mar 25;24 (1) :114.|Cancer Cell. 2024 Apr 8;42 (4) :682-700.e12.|Cell Commun Signal. 2025 Nov 12;23 (1) :492.|Cell Commun Signal. 2025 Sep 30;23 (1) :402.|Cell Death Differ. 2021 Mar;28 (3) :1001-1012.|Cell Death Dis. 2024 Dec 24;15 (12) :930.|Cell Death Discov. 2021 Oct 4;7 (1) :273.|Cell Discov. 2025 Mar 11;11 (1) :22.|Cell Mol Life Sci. 2025 Aug 8;82 (1) :303.|Chin Herb Med. 2025 Jul 23.|Chin Med. 2022 Feb 21;17 (1) :25.|Clin Epigenetics. 2023 Nov 11;15 (1) :182.|CNS Neurosci Ther. 2022 Nov;28 (11) :1883-1894.|Commun Biol. 2025 Jul 29;8 (1) :1127.|Commun Biol. 2025 Mar 8;8 (1) :396.|Curr Med Sci. 2024 Jun;44 (3) :519-528.|Drug Dev Res. 2023 Dec;84 (8) :1751-1763.|Drug Dev Res. 2025 Nov;86 (7) :e70175.|EMBO Mol Med. 2024 Apr;16 (4) :870-884.|Eur Rev Med Pharmaco. 2021; 25 (2) : 787-794.|Fish Shellfish Immunol. 2020 Feb;97:455-464.|Front Biosci (Landmark Ed) . 2024 Sep 24;29 (9) :336.|Front Cell Dev Biol. 2020 Sep 18:8:858.|Front Pharmacol. 2018 Jun 21:9:660.|Front Pharmacol. 2021 Dec 16:12:774316.|Immunol Lett. 2019 Feb:206:33-40.|Int Immunopharmacol. 2024 Sep 18;142 (Pt B) :113186.|Int J Clin Exp Med. 2016;9 (8) :15892-15899.|Int J Mol Med. 2019 Feb;43 (2) :993-1002. |iScience. 2023 May 29;26 (7) :106994.|J Biol Chem. 2024 Feb;300 (2) :105605.|J Cell Biochem. 2019 Oct;120 (10) :17872-17886. |J Cell Mol Med. 2021 Dec;25 (24) :11113-11127.|J Cell Mol Med. 2024 Nov;28 (22) :e70214.|J Cell Mol Med. 2025 Mar;29 (5) :e70486.|J Cell Physiol. 2020 Jan;235 (1) :429-441.|J Cell Physiol. 2024 Mar;239 (3) :e31062.|J Clin Transl Hepatol. May 26, 2022.|J Dent Sci. 2023 Apr;18 (2) :865-871.|J Ethnopharmacol. 2023 May 10:307:116243.|J Invest Dermatol. 2019 Jan;139 (1) :224-234.|J Pers Med. 2022 Mar 2;12 (3) :385.|Life Sci. 2023 May 1:320:121540.|Life Sci. 2025 May 22:376:123755.|mBio. 2025 Jul 31:e0136625.|Med Sci Monit. 2018 Nov 18:24:8290-8297.|MedComm (2020) . 2025 Mar 27;6 (4) :e70148.|Meharry Medical College. 2024.|Mol Immunol. 2018 Nov:103:173-181.|Mol Med Rep. 2019 Aug;20 (2) :1605-1612.|Nat Commun. 2025 Oct 3;16 (1) :8826.|Neural Regen Res. 2024 Jan;19 (1) :180-189.|NPJ Regen Med. 2020 Oct 30;5 (1) :19.|Nucleic Acids Res. 2023 Apr 11;51 (6) :2655-2670.|Oncogenesis. 2021 Oct 27;10 (10) :72.|Parasit Vectors. 2020 Apr 3;13 (1) :164.|Phytother Res. 2023 Feb;37 (2) :717-730.|Redox Biol. 2023 Jun:62:102709.|Research Square Preprint. 2020 Nov.|Research Square Preprint. 2021 May.|Research Square Preprint. 2023 Jun 19.|Research Square Print. September 15th, 2022.|Sci Rep. 2017 Sep 8;7 (1) :11006. |Sci Rep. 2022 Feb 23;12 (1) :3053.|Stem Cell Res. 2020 Dec;49:102099.|Tissue Cell. 2025 Jul 29:97:103061.|Tissue Eng Regen Med. 2021 Dec;18 (6) :963-973.|Tissue Eng Regen Med. 2022 Jun;19 (3) :577-588.|Wright State University. 2023 Feb 23.|Antioxidants (Basel) . 2022 Dec 15;11 (12) :2469.|Cell Biol Int. 2023 Apr;47 (4) :754-767.|Cell Transplant. 2023 Jan-Dec:32:9636897231162526.|Cell Transplant. 2023 Jan-Dec:32:9636897231177356.|FASEB J. 2022 Dec;36 (12) :e22625.|J ImmunoTher Cancer. 2020 Aug;8 (2) :e000422. |J Transl Med. 2025 Jul 10;23 (1) :763.|Theranostics. 2021 May 13;11 (14) :7110-7125.

• CAS Number:

  521984-48-5