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MedKoo Cat#: 584475 | Name: SIS3 HCl
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

SIS3 HCl
SIS3 HCl
CAS#521984-48-5

Theoretical Analysis

MedKoo Cat#: 584475

Name: SIS3 HCl

CAS#: 521984-48-5

Chemical Formula: C28H28ClN3O3

Exact Mass: 0.0000

Molecular Weight: 490.00

Elemental Analysis: C, 68.63; H, 5.76; Cl, 7.23; N, 8.58; O, 9.80

Price and Availability

Size Price Availability Quantity
2mg USD 450.00 2 weeks
5mg USD 750.00 2 weeks
25mg USD 1,450.00 2 weeks
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Related CAS #
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Synonym
SIS3 HCl; SIS3 Hydrochloride;
IUPAC/Chemical Name
2-Propen-1-one, 1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-, hydrochloride (1:1), (2E)-
InChi Key
CDKIEBFIMCSCBB-CALJPSDSSA-N
InChi Code
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+;
SMILES Code
O=C(N1CC2=C(C=C(OC)C(OC)=C2)CC1)/C=C/C3=C(C4=CC=CC=C4)N(C)C5=NC=CC=C53.[H]Cl
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.03.00
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
SIS3 selectively inhibits TGF-β and activin signaling by suppressing Smad3 phosphorylation (IC50 = 3 µM) without affecting the MAPK/p38, ERK, or PI3-kinase signaling pathways. It has been shown to reduce TGF-β1-induced type 1 procollagen expression and myofibroblast differentiation in normal dermal fibroblasts as well as scleroderma fibroblasts.
In vitro activity:
This study proposes repurposing SIS3 as a potent modulator of ABCB1 and ABCG2 for overcoming multidrug resistance (MDR) in cancer cells. In cancer cell lines, SIS3 effectively inhibits the transport function of ABCB1 and ABCG2, enhances drug-induced apoptosis, and resensitizes MDR cancer cells to chemotherapy at non-toxic concentrations. Combining SIS3 with standard chemotherapeutic agents may offer a promising strategy for patients with MDR tumors. Reference: Cancer Lett. 2018 Oct 1;433:259-272. https://pubmed.ncbi.nlm.nih.gov/30026175/
In vivo activity:
SIS3 may serve as a promising treatment for chronic obstructive sialadenitis. SIS3 protected duct-ligated submandibular glands (SMGs) against fibrosis and dysfunction by inhibiting the TGF-β/SMAD3 signaling and inflammatory cytokine expression in micewith ligated dominant duct in SMG. Reference: J Dent Sci. 2023 Apr;18(2):865-871. https://pubmed.ncbi.nlm.nih.gov/37021213/

Preparing Stock Solutions

The following data is based on the product molecular weight 490.00 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Huang Z, Zhang C, Zhu K, Hu J, Xu E, Ma X, Wang Y, Zhu Y, Zhu J. (E)-SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment. Drug Dev Res. 2023 Dec;84(8):1751-1763. doi: 10.1002/ddr.22120. Epub 2023 Oct 2. PMID: 37784254. 2. Wu CP, Murakami M, Hsiao SH, Liu TC, Yeh N, Li YQ, Hung TH, Wu YS, Ambudkar SV. SIS3, a specific inhibitor of Smad3 reverses ABCB1- and ABCG2-mediated multidrug resistance in cancer cell lines. Cancer Lett. 2018 Oct 1;433:259-272. doi: 10.1016/j.canlet.2018.07.004. Epub 2018 Jul 6. PMID: 30026175; PMCID: PMC6084781. 3. Li H, Wang G, Hu M, Dai R, Li C, Cao Y. Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice. J Dent Sci. 2023 Apr;18(2):865-871. doi: 10.1016/j.jds.2023.02.004. Epub 2023 Feb 16. PMID: 37021213; PMCID: PMC10068496. 4. Pan W, Zheng L, Gao J, Ye L, Chen Z, Liu S, Pan B, Fang J, Lai H, Zhang Y, Ni K, Lou C, He D. SIS3 suppresses osteoclastogenesis and ameliorates bone loss in ovariectomized mice by modulating Nox4-dependent reactive oxygen species. Biochem Pharmacol. 2022 Jan;195:114846. doi: 10.1016/j.bcp.2021.114846. Epub 2021 Nov 18. PMID: 34801525.
In vitro protocol:
1. Huang Z, Zhang C, Zhu K, Hu J, Xu E, Ma X, Wang Y, Zhu Y, Zhu J. (E)-SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment. Drug Dev Res. 2023 Dec;84(8):1751-1763. doi: 10.1002/ddr.22120. Epub 2023 Oct 2. PMID: 37784254. 2. Wu CP, Murakami M, Hsiao SH, Liu TC, Yeh N, Li YQ, Hung TH, Wu YS, Ambudkar SV. SIS3, a specific inhibitor of Smad3 reverses ABCB1- and ABCG2-mediated multidrug resistance in cancer cell lines. Cancer Lett. 2018 Oct 1;433:259-272. doi: 10.1016/j.canlet.2018.07.004. Epub 2018 Jul 6. PMID: 30026175; PMCID: PMC6084781.
In vivo protocol:
1. Li H, Wang G, Hu M, Dai R, Li C, Cao Y. Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice. J Dent Sci. 2023 Apr;18(2):865-871. doi: 10.1016/j.jds.2023.02.004. Epub 2023 Feb 16. PMID: 37021213; PMCID: PMC10068496. 2. Pan W, Zheng L, Gao J, Ye L, Chen Z, Liu S, Pan B, Fang J, Lai H, Zhang Y, Ni K, Lou C, He D. SIS3 suppresses osteoclastogenesis and ameliorates bone loss in ovariectomized mice by modulating Nox4-dependent reactive oxygen species. Biochem Pharmacol. 2022 Jan;195:114846. doi: 10.1016/j.bcp.2021.114846. Epub 2021 Nov 18. PMID: 34801525.
1: Jang IH, Kruglov V, Cholensky SH, Smith DM, Carey A, Bai S, Nottoli T, Bernlohr DA, Camell CD. GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging. bioRxiv [Preprint]. 2024 Sep 25:2024.09.23.614375. doi: 10.1101/2024.09.23.614375. PMID: 39386655; PMCID: PMC11463477. 2: Zhang W, Zhu L, Fang F, Zhang F, Wang R, Yang K, Liu Y, Cui X. Activin A plays an essential role in migration and proliferation of hepatic stellate cells via Smad3 and calcium signaling. Sci Rep. 2024 Sep 3;14(1):20419. doi: 10.1038/s41598-024-71304-7. PMID: 39223291; PMCID: PMC11369249. 3: Hamczyk MR, Nevado RM, Gonzalo P, Andrés-Manzano MJ, Nogales P, Quesada V, Rosado A, Torroja C, Sánchez-Cabo F, Dopazo A, Bentzon JF, López-Otín C, Andrés V. Endothelial-to-Mesenchymal Transition Contributes to Accelerated Atherosclerosis in Hutchinson-Gilford Progeria Syndrome. Circulation. 2024 Nov 12;150(20):1612-1630. doi: 10.1161/CIRCULATIONAHA.123.065768. Epub 2024 Aug 29. PMID: 39206565. 4: Huang J, Ye J, Gao Y, Wang Y, Zhao Q, Lou T, Lai W. Identification of proteins related to SIS3 by iTRAQ and PRM-based comparative proteomic analysis in cisplatin-induced acute kidney injury. PeerJ. 2024 Jun 4;12:e17485. doi: 10.7717/peerj.17485. PMID: 38854800; PMCID: PMC11160430. 5: Jia J, Tan R, Xu L, Wang H, Li J, Su H, Zhong X, Liu P, Wang L. Hederagenin improves renal fibrosis in diabetic nephropathy by regulating Smad3/NOX4/SLC7A11 signaling-mediated tubular cell ferroptosis. Int Immunopharmacol. 2024 Jun 30;135:112303. doi: 10.1016/j.intimp.2024.112303. Epub 2024 May 21. PMID: 38776855. 6: Ye J, Hua Z, Xiao J, Shao Y, Li S, Yin H, Wu M, Rong Y, Hong B, Guo Y, Ma Y, Wang J. p-Smad3 differentially regulates the cytological behavior of osteoclasts before and after osteoblasts maturation. Mol Biol Rep. 2024 Apr 17;51(1):525. doi: 10.1007/s11033-024-09400-0. PMID: 38632128. 7: Qiu ZW, Zhong YT, Lu ZM, Yan N, Kong RJ, Huang JQ, Li ZF, Nie JM, Li R, Cheng H. Breaking Physical Barrier of Fibrotic Breast Cancer for Photodynamic Immunotherapy by Remodeling Tumor Extracellular Matrix and Reprogramming Cancer- Associated Fibroblasts. ACS Nano. 2024 Apr 2;18(13):9713-9735. doi: 10.1021/acsnano.4c01499. Epub 2024 Mar 20. PMID: 38507590. 8: Bhattacharyya S, Tobacman JK. SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK. Signal Transduct Target Ther. 2024 Feb 14;9(1):39. doi: 10.1038/s41392-024-01741-3. PMID: 38355690; PMCID: PMC10866996. 9: He H, Wang H, Chen X, Zhong Y, Huang XR, Ma RC, Wang C, Lan HY. Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling. Int J Biol Sci. 2024 Jan 1;20(1):200-217. doi: 10.7150/ijbs.87820. PMID: 38164169; PMCID: PMC10750285. 10: Huo D, Bi XY, Zeng JL, Dai DM, Dong XL. Drugs targeting TGF-β/Notch interaction attenuate hypertrophic scar formation by optic atrophy 1-mediated mitochondrial fusion. Mol Cell Biochem. 2024 Nov;479(11):3049-3061. doi: 10.1007/s11010-023-04912-y. Epub 2023 Dec 29. PMID: 38158493. 11: Wang S, Tan X, Zhou Q, Geng P, Wang J, Zou P, Deng A, Hu J. Retraction Note: Co-delivery of doxorubicin and SIS3 by folate-targeted polymeric micelles for overcoming tumor multidrug resistance. Drug Deliv Transl Res. 2024 Jul;14(7):2019. doi: 10.1007/s13346-023-01489-3. PMID: 38051476. 12: Wu Q, Kang L, Lin Z. A Machine Learning Study on High Thermal Conductivity Assisted to Discover Chalcogenides with Balanced Infrared Nonlinear Optical Performance. Adv Mater. 2024 Feb;36(6):e2309675. doi: 10.1002/adma.202309675. Epub 2023 Dec 6. PMID: 37929600. 13: Luo J, Xu Y, Chu H, Yang L, Song Z, Jin W, Wang X, Xue Y. Research on the Performance of Superhydrophobic Cement-Based Materials Based on Composite Hydrophobic Agents. Materials (Basel). 2023 Oct 7;16(19):6592. doi: 10.3390/ma16196592. PMID: 37834729; PMCID: PMC10574258. 14: Wang X, Zhu L, Zhou J, Zhao L, Li J, Liu C. Drug-loaded hybrid hydrogels for sonodynamic-chemodyanmic therapy and tumor metastasis suppression. Front Bioeng Biotechnol. 2023 Sep 18;11:1281157. doi: 10.3389/fbioe.2023.1281157. PMID: 37790250; PMCID: PMC10544978. 15: Huang Z, Zhang C, Zhu K, Hu J, Xu E, Ma X, Wang Y, Zhu Y, Zhu J. (E)-SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment. Drug Dev Res. 2023 Dec;84(8):1751-1763. doi: 10.1002/ddr.22120. Epub 2023 Oct 2. PMID: 37784254. 16: Dan Hu Q, Wang HL, Liu J, He T, Tan RZ, Zhang Q, Su HW, Kantawong F, Lan HY, Wang L. Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition. Adv Sci (Weinh). 2023 Nov;10(32):e2304360. doi: 10.1002/advs.202304360. Epub 2023 Sep 25. PMID: 37749872; PMCID: PMC10646233. 17: Song A, Zhang S, Zhao X, Wu S, Qi X, Gao S, Qi J, Li P, Tan J. Exosomes derived from menstrual blood stromal cells ameliorated premature ovarian insufficiency and granulosa cell apoptosis by regulating SMAD3/AKT/MDM2/P53 pathway via delivery of thrombospondin-1. Biomed Pharmacother. 2023 Oct;166:115319. doi: 10.1016/j.biopha.2023.115319. Epub 2023 Aug 11. PMID: 37573658. 18: Bidoki NH, Zera KA, Nassar H, Drag LL, Mlynash M, Osborn E, Musabbir M, Kim DE, Paula Mendez M, Lansberg MG, Aghaeepour N, Buckwalter MS. Machine learning models of plasma proteomic data predict mood in chronic stroke and tie it to aberrant peripheral immune responses. Brain Behav Immun. 2023 Nov;114:144-153. doi: 10.1016/j.bbi.2023.08.002. Epub 2023 Aug 7. PMID: 37557961; PMCID: PMC10792657. 19: He H, Zhong Y, Wang H, Tang PM, Xue VW, Chen X, Chen J, Huang X, Wang C, Lan H. Smad3 Mediates Diabetic Dyslipidemia and Fatty Liver in db/db Mice by Targeting PPARδ. Int J Mol Sci. 2023 Jul 13;24(14):11396. doi: 10.3390/ijms241411396. PMID: 37511155; PMCID: PMC10380492. 20: Zhang Z, Song Z, Luo L, Zhu Z, Zuo X, Ju C, Wang X, Ma Y, Wu T, Yao Z, Zhou J, Chen B, Ding T, Wang Z, Hu X. Photobiomodulation inhibits the expression of chondroitin sulfate proteoglycans after spinal cord injury via the Sox9 pathway. Neural Regen Res. 2024 Jan;19(1):180-189. doi: 10.4103/1673-5374.374136. PMID: 37488865; PMCID: PMC10479858.

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Climiqualine

Climiqualine