MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 406135 | Name: SB505124
Featured New

Description:

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

SB505124:  SB505124 is a selective inhibitor of transforming growth factor-β type I receptor (ALK5, ALK4 and ALK7) with potential anticancer activity. SB505124 selectively inhibits signaling from TGF-β and activin; does not inhibit other ALK family members. SB-505124 selectively and concentration-dependently inhibits ALK4-, ALK5-, and ALK 7-dependent activation of downstream cytoplasmic signal transducers, Smad2 and Smad3, and of TGF-beta-induced mitogen-activated protein kinase pathway components but does not alter ALK1, ALK2, ALK3 or ALK6-induced Smad signaling.

Chemical Structure

SB505124
SB505124
CAS#694433-59-5 (free base)

Theoretical Analysis

MedKoo Cat#: 406135

Name: SB505124

CAS#: 694433-59-5 (free base)

Chemical Formula: C20H21N3O2

Exact Mass: 335.1634

Molecular Weight: 335.40

Elemental Analysis: C, 71.62; H, 6.31; N, 12.53; O, 9.54

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 450.00 Ready to ship
200mg USD 750.00 Ready to ship
500mg USD 1,650.00 Ready to ship
1g USD 2,850.00 Ready to ship
2g USD 4,650.00 Ready to ship
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
356559-13-2 (HCl) 694433-59-5 (free base)
Synonym
SB505124; SB-505124; SB 505124
IUPAC/Chemical Name
2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(tert-butyl)-1H-imidazol-5-yl)-6-methylpyridine
InChi Key
WGZOTBUYUFBEPZ-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H21N3O2/c1-12-6-5-7-14(21-12)18-17(22-19(23-18)20(2,3)4)13-8-9-15-16(10-13)25-11-24-15/h5-10H,11H2,1-4H3,(H,22,23)
SMILES Code
CC1=CC=CC(C2=C(C3=CC=C(OCO4)C4=C3)N=C(C(C)(C)C)N2)=N1
Appearance
Light peach to pale pink 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, not in water
Shelf Life
>5 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
2934.99.9001
More Info
        
Biological target:
SB-505124 is a selective inhibitor of TGF-β Receptor type I receptors (ALK4, ALK5, ALK7), with IC50s of 129 nM and 47 nM for ALK4, ALK5, respectively, but it does not inhibit ALK1, 2, 3, or 6.
In vitro activity:
Pharmacological inhibition of the ACVR1C receptor using SB505124, a selective inhibitor of ALK4/5/7 receptors, significantly reduced growth (Figure 3a, c, e) and invasion (Figure 3b, d, f) of cultured retinoblastoma cells in a dose-dependent manner. In WERI Rb1 cells, growth was potently suppressed, starting at 2 µM after 3, 5, and 7 days of treatment (Figure 3a). Y79 growth was almost completely suppressed at concentrations ≥ 1 µM (Figure 3c), while HSJD-RBVS-10 cells were somewhat less responsive to SB505124-mediated growth inhibition (Figure 3e). Nevertheless, SB505124 potently suppressed invasion of all three lines in a dose-dependent manner, as found by transwell invasion assay, with more than 70% inhibition in the ability of the cells to invade through a Matrigel-coated filter at concentrations ≥ 3 µM (Figure 3b, d, f). Reference: Oncogene. 2019 Mar; 38(12): 2056–2075. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430693/
In vivo activity:
In this study, SB505124 was found to be effective in rescuing symptoms during CRA (cancer-related anemia). SB505124 is a small molecule inhibitor of the TGFβ type I receptor serine/threonine kinase known as activin receptor-like kinase (ALK). Indeed, this study observed that SB505124 significantly rescued erythrocyte reduction, ameliorated the hindered hematopoiesis, and improved the HSC niche in the bone marrow. Results suggest that the TGFβ signaling pathway could be targeted to restore the HSC niche and rescue CRA. Several TGFβ pathway inhibitors are currently under clinical trials and have shown acceptable safety, tolerability, and efficacy for slowing the progression of solid tumors and myelodysplastic syndrome. These details, combined with present novel findings in the LLC-bearing mouse model, suggest that SB505124 is a safe and effective treatment that could be developed for CRA and potentially other cancer-related disorders. Reference: Stem Cell Res Ther. 2021; 12: 65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814632/
Solvent mg/mL mM
Solubility
DMSO 57.7 172.09
DMF 20.0 59.63
Ethanol 43.5 129.70
Ethanol:PBS (pH 7.2) (1:1) 0.5 1.49
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 335.40 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. Asnaghi L, White DT, Key N, Choi J, Mahale A, Alkatan H, Edward DP, Elkhamary SM, Al-Mesfer S, Maktabi A, Hurtado CG, Lee GY, Carcaboso AM, Mumm JS, Safieh LA, Eberhart CG. ACVR1C/SMAD2 signaling promotes invasion and growth in retinoblastoma. Oncogene. 2019 Mar;38(12):2056-2075. doi: 10.1038/s41388-018-0543-2. Epub 2018 Nov 6. PMID: 30401983; PMCID: PMC6430693. 2. Liu Y, Sharma T, Chen IP, Reichenberger E, Ueki Y, Arif Y, Parisi D, Maye P. Rescue of a cherubism bone marrow stromal culture phenotype by reducing TGFβ signaling. Bone. 2018 Jun;111:28-35. doi: 10.1016/j.bone.2018.03.009. Epub 2018 Mar 9. PMID: 29530719; PMCID: PMC5924722. 3. Wang B, Wang Y, Chen H, Yao S, Lai X, Qiu Y, Cai J, Huang Y, Wei X, Guan Y, Wang T, Wang J, Xiang AP. Inhibition of TGFβ improves hematopoietic stem cell niche and ameliorates cancer-related anemia. Stem Cell Res Ther. 2021 Jan 18;12(1):65. doi: 10.1186/s13287-020-02120-9. PMID: 33461597; PMCID: PMC7814632. 4. Zhang H, Chen S, Shang C, Wu X, Wang Y, Li G. Interplay between Lefty and Nodal signaling is essential for the organizer and axial formation in amphioxus embryos. Dev Biol. 2019 Dec 1;456(1):63-73. doi: 10.1016/j.ydbio.2019.08.006. Epub 2019 Aug 13. PMID: 31419410.
In vitro protocol:
1. Asnaghi L, White DT, Key N, Choi J, Mahale A, Alkatan H, Edward DP, Elkhamary SM, Al-Mesfer S, Maktabi A, Hurtado CG, Lee GY, Carcaboso AM, Mumm JS, Safieh LA, Eberhart CG. ACVR1C/SMAD2 signaling promotes invasion and growth in retinoblastoma. Oncogene. 2019 Mar;38(12):2056-2075. doi: 10.1038/s41388-018-0543-2. Epub 2018 Nov 6. PMID: 30401983; PMCID: PMC6430693. 2. Liu Y, Sharma T, Chen IP, Reichenberger E, Ueki Y, Arif Y, Parisi D, Maye P. Rescue of a cherubism bone marrow stromal culture phenotype by reducing TGFβ signaling. Bone. 2018 Jun;111:28-35. doi: 10.1016/j.bone.2018.03.009. Epub 2018 Mar 9. PMID: 29530719; PMCID: PMC5924722.
In vivo protocol:
1. Wang B, Wang Y, Chen H, Yao S, Lai X, Qiu Y, Cai J, Huang Y, Wei X, Guan Y, Wang T, Wang J, Xiang AP. Inhibition of TGFβ improves hematopoietic stem cell niche and ameliorates cancer-related anemia. Stem Cell Res Ther. 2021 Jan 18;12(1):65. doi: 10.1186/s13287-020-02120-9. PMID: 33461597; PMCID: PMC7814632. 2. Zhang H, Chen S, Shang C, Wu X, Wang Y, Li G. Interplay between Lefty and Nodal signaling is essential for the organizer and axial formation in amphioxus embryos. Dev Biol. 2019 Dec 1;456(1):63-73. doi: 10.1016/j.ydbio.2019.08.006. Epub 2019 Aug 13. PMID: 31419410.
1: Ali D, Okla M, Abuelreich S, Vishnubalaji R, Ditzel N, Hamam R, Kowal JM, Sayed A, Aldahmash A, Alajez NM, Kassem M. Apigenin and Rutaecarpine reduce the burden of cellular senescence in bone marrow stromal stem cells. Front Endocrinol (Lausanne). 2024 Apr 4;15:1360054. doi: 10.3389/fendo.2024.1360054. PMID: 38638133; PMCID: PMC11024792. 2: Marín-Aquino LA, Mora-García ML, Moreno-Lafont MC, García-Rocha R, Montesinos-Montesinos JJ, López-Santiago R, Sánchez-Torres LE, Torres-Pineda DB, Weiss-Steider B, Hernández-Montes J, Don-López CA, Monroy-García A. Adenosine increases PD-L1 expression in mesenchymal stromal cells derived from cervical cancer through its interaction with A2AR/A2BR and the production of TGF-β1. Cell Biochem Funct. 2024 Apr;42(3):e4010. doi: 10.1002/cbf.4010. PMID: 38613217. 3: García-Rocha R, Monroy-García A, Vázquez-Cruz AL, Marín-Aquino LA, Weiss- Steider B, Hernández-Montes J, Don-López CA, Molina-Castillo G, Mora-García ML. Adenosine Increases the Immunosuppressive Capacity of Cervical Cancer Cells by Increasing PD-L1 Expression and TGF-β Production through Its Interaction with A2AR/A2BR. Pharmaceuticals (Basel). 2024 Mar 19;17(3):397. doi: 10.3390/ph17030397. PMID: 38543183; PMCID: PMC10974506. 4: Du M, Qu Y, Qin L, Zheng J, Sun W. The cell death-related genes machine learning model for precise therapy and clinical drug selection in hepatocellular carcinoma. J Cell Mol Med. 2024 Apr;28(7):e18168. doi: 10.1111/jcmm.18168. PMID: 38494848; PMCID: PMC10945081. 5: Wang W, Chen P, Yuan S. Programmed cell death-index (PCDi) as a prognostic biomarker and predictor of drug sensitivity in cervical cancer: a machine learning-based analysis of mRNA signatures. J Cancer. 2024 Jan 20;15(5):1378-1396. doi: 10.7150/jca.91798. PMID: 38356704; PMCID: PMC10861809. 6: Antoniadis A, Wegrzyn J, Omoumi P, Loisay L, Hügle T, Geurts J. Elevated secretion of pro-collagen I-alpha and vascular endothelial growth factor as biomarkers of acetabular labrum degeneration and calcification in hip osteoarthritis: An explant study. J Orthop Translat. 2023 Dec 26;44:19-25. doi: 10.1016/j.jot.2023.08.007. PMID: 38179125; PMCID: PMC10765489. 7: Taga H, Kishida T, Inoue Y, Yamamoto K, Kotani SI, Masashi T, Ukimura O, Mazda O. TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients. PLoS One. 2023 Nov 6;18(11):e0293983. doi: 10.1371/journal.pone.0293983. PMID: 37931000; PMCID: PMC10627456. 8: Thielen NGM, van Caam APM, V Beuningen HM, Vitters EL, van den Bosch MHJ, Koenders MI, van de Loo FAJ, Blaney Davidson EN, van der Kraan PM. Separating friend from foe: Inhibition of TGF-β-induced detrimental SMAD1/5/9 phosphorylation while maintaining protective SMAD2/3 signaling in OA chondrocytes. Osteoarthritis Cartilage. 2023 Nov;31(11):1481-1490. doi: 10.1016/j.joca.2023.08.004. Epub 2023 Aug 29. PMID: 37652257. 9: Zhang Y, Wang B, Song H, Han M. GLIS3, a novel prognostic indicator of gastric adenocarcinoma, contributes to the malignant biological behaviors of tumor cells via modulating TGF-β1/TGFβR1/Smad1/5 signaling pathway. Cytokine. 2023 Oct;170:156342. doi: 10.1016/j.cyto.2023.156342. Epub 2023 Aug 30. PMID: 37651918. 10: Jiang ZY, Ma XM, Luan XH, Liuyang ZY, Hong YY, Dai Y, Dong QH, Wang GY. BMI-1 activates hepatic stellate cells to promote the epithelial-mesenchymal transition of colorectal cancer cells. World J Gastroenterol. 2023 Jun 21;29(23):3606-3621. doi: 10.3748/wjg.v29.i23.3606. PMID: 37398890; PMCID: PMC10311613. 11: Kanal HD, Levison SW. Neuroprotective Effects of Delayed TGF-β1 Receptor Antagonist Administration on Perinatal Hypoxic-Ischemic Brain Injury. Dev Neurosci. 2024;46(3):188-200. doi: 10.1159/000531650. Epub 2023 Jun 22. PMID: 37348472. 12: Almuraikhi N. Inhibition of TGF-β type I receptor by SB505124 down-regulates osteoblast differentiation and mineralization of human mesenchymal stem cells. Cell Biochem Funct. 2023 Jul;41(5):564-572. doi: 10.1002/cbf.3812. Epub 2023 May 26. PMID: 37232472. 13: Klück V, Cabău G, Mies L, Bukkems F, van Emst L, Bakker R, van Caam A; HINT consortium; Crişan TO, Joosten LAB. TGF-β is elevated in hyperuricemic individuals and mediates urate-induced hyperinflammatory phenotype in human mononuclear cells. Arthritis Res Ther. 2023 Feb 27;25(1):30. doi: 10.1186/s13075-023-03001-1. PMID: 36850003; PMCID: PMC9969669. 14: Cadenas-Martin M, Arnalich-Montiel F, Miguel MP. Derivation of Limbal Stem Cells from Human Adult Mesenchymal Stem Cells for the Treatment of Limbal Stem Cell Deficiency. Int J Mol Sci. 2023 Jan 25;24(3):2350. doi: 10.3390/ijms24032350. PMID: 36768672; PMCID: PMC9916480. 15: Ilg MM, Lapthorn AR, Ralph DJ, Cellek S. Phenotypic screening of 1,953 FDA- approved drugs reveals 26 hits with potential for repurposing for Peyronie's disease. PLoS One. 2022 Dec 12;17(12):e0277646. doi: 10.1371/journal.pone.0277646. PMID: 36508413; PMCID: PMC9744312. 16: Yang Y, Zhang C, Song Y, Li Y, Li P, Huang M, Meng F, Zhang M. Small- molecule activators specific to adenine base editors through blocking the canonical TGF-β pathway. Nucleic Acids Res. 2022 Sep 23;50(17):9632-9646. doi: 10.1093/nar/gkac742. PMID: 36043443; PMCID: PMC9508813. 17: Tao Y, Wei L, You H. Ferroptosis-related gene signature predicts the clinical outcome in pediatric acute myeloid leukemia patients and refines the 2017 ELN classification system. Front Mol Biosci. 2022 Aug 11;9:954524. doi: 10.3389/fmolb.2022.954524. PMID: 36032681; PMCID: PMC9403410. 18: Wang B, Bai J, Tian B, Chen H, Yang Q, Chen Y, Xu J, Zhang Y, Dai H, Ma Q, Fei Z, Wang H, Xu F, Zhou X, Wang C. Genetically Engineered Hematopoietic Stem Cells Deliver TGF-β Inhibitor to Enhance Bone Metastases Immunotherapy. Adv Sci (Weinh). 2022 Oct;9(28):e2201451. doi: 10.1002/advs.202201451. Epub 2022 Aug 10. PMID: 35948516; PMCID: PMC9534984. 19: Liu X, Xu C, Lou J, Du C, Tang L, Chen X. Platelet TGF-β1 inhibits the migration and proliferation of smooth muscle cells in aneurysms. Cytokine. 2022 Oct;158:155969. doi: 10.1016/j.cyto.2022.155969. Epub 2022 Aug 2. PMID: 35930963. 20: Ximei X, Yiqun L, Zhikun Z, Yueli N, Xiuli L, Wei S, Tao W, Pan W, Xiyu L, Yong H, Yongxiang Z, Lu G, Liping Z, Qiaoying C, Jian H. Targeted Anti- Hepatocellular Carcinoma Research of Targeted Peptides Combined with Drug-Loaded Cell-Derived Microparticles. J Biomed Nanotechnol. 2022 Apr 1;18(4):1009-1018. doi: 10.1166/jbn.2022.3311. PMID: 35854442.