WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406135
CAS#: 694433-59-5
Description: 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.
MedKoo Cat#: 406135
Name: SB505124
CAS#: 694433-59-5
Chemical Formula: C20H21N3O2
Exact Mass: 335.16338
Molecular Weight: 335.4
Elemental Analysis: C, 71.62; H, 6.31; N, 12.53; O, 9.54
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
| 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 57.72 | 172.09 | |
| DMF | 20.0 | 59.63 | |
| Ethanol | 43.5 | 129.7 | |
| Ethanol:PBS (pH 7.2) (1:1) | 0.5 | 1.49 |
The following data is based on the product molecular weight 335.4 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.
| 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. |
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