WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406817
CAS#: 627536-09-8
Description: SD-208, also known as TGF-β RI Kinase Inhibitor V, is a novel protein kinase D inhibitor. SD-208 blocks prostate cancer cell proliferation and tumor growth in vivo by inducing G2/M cell cycle arrest. SD-208 reduces the development and progression of melanoma bone metastases. SD-208 inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo.
MedKoo Cat#: 406817
Name: SD-208
CAS#: 627536-09-8
Chemical Formula: C17H10ClFN6
Exact Mass: 352.064
Molecular Weight: 352.7574
Elemental Analysis: C, 57.88; H, 2.86; Cl, 10.05; F, 5.39; N, 23.82
Related CAS #: 627536-09-8
Synonym: SD-208; SD 208; SD208; TGF-β RI Kinase Inhibitor V.
IUPAC/Chemical Name: 2-(5-chloro-2-fluorophenyl)-N-4-pyridinyl-4-pteridinamine
InChi Key: BERLXWPRSBJFHO-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H10ClFN6/c18-10-1-2-13(19)12(9-10)15-24-16-14(21-7-8-22-16)17(25-15)23-11-3-5-20-6-4-11/h1-9H,(H,20,22,23,24,25)
SMILES Code: FC1=CC=C(Cl)C=C1C2=NC(NC3=CC=NC=C3)=C4N=CC=NC4=N2
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: >2 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: | SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, >100-fold selectivity over TGF-βRII. |
| In vitro activity: | The effects of a novel TGF-beta receptor (TGF-betaR) I kinase inhibitor, SD-208, on the growth and immunogenicity of murine SMA-560 and human LN-308 glioma cells in vitro are characterized. SD-208 inhibits the growth inhibition of TGF-beta-sensitive CCL64 cells mediated by recombinant TGF-beta1 or TGF-beta2 or of TGF-beta-containing glioma cell supernatant at an EC(50) of 0.1 mumol/L. SD-208 blocks autocrine and paracrine TGF-beta signaling in glioma cells as detected by the phosphorylation of Smad2 or TGF-beta reporter assays and strongly inhibits constitutive and TGF-beta-evoked migration and invasion, but not viability or proliferation. Peripheral blood lymphocytes or purified T cells, cocultured with TGF-beta-releasing LN-308 glioma cells in the presence of SD-208, exhibit enhanced lytic activity against LN-308 targets. The release of interferon gamma and tumor necrosis factor alpha by these immune effector cells is enhanced by SD-208, whereas the release of interleukin 10 is reduced. SD-208 restores the lytic activity of polyclonal natural killer cells against glioma cells in the presence of recombinant TGF-beta or of TGF-beta-containing glioma cell supernatant. Reference: Cancer Res. 2004 Nov 1;64(21):7954-61. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15520202 |
| In vivo activity: | The effects of SD-208 on the growth of and immune response to intracranial SMA-560 gliomas were studied in syngeneic VM/Dk mice in vivo. The oral bioavailability of SD-208 was verified by demonstrating the inhibition of TGF-beta-induced Smad phosphorylation in spleen and brain. Systemic SD-208 treatment initiated 3 days after the implantation of SMA-560 cells into the brains of syngeneic VM/Dk mice prolongs their median survival from 18.6 to 25.1 days. Histologic analysis revealed no difference in blood vessel formation, proliferation, or apoptosis. However, animals responding to SD-208 showed an increased tumor infiltration by natural killer cells, CD8 T cells, and macrophages. These data define TGF-beta receptor I kinase inhibitors such as SD-208 as promising novel agents for the treatment of human malignant glioma and other conditions associated with pathological TGF-beta activity. Reference: Cancer Res. 2004 Nov 1;64(21):7954-61. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15520202 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 9.09 | 25.77 |
The following data is based on the product molecular weight 352.7574 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 |
| In vitro protocol: | 1. Uhl M, Aulwurm S, Wischhusen J, Weiler M, Ma JY, Almirez R, Mangadu R, Liu YW, Platten M, Herrlinger U, Murphy A, Wong DH, Wick W, Higgins LS, Weller M. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004 Nov 1;64(21):7954-61. doi: 10.1158/0008-5472.CAN-04-1013. PMID: 15520202. 2. Fadakar P, Akbari A, Ghassemi F, Mobini GR, Mohebi M, Bolhassani M, Abed Khojasteh H, Heidari M. Evaluation of SD-208, a TGF-β-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma. Acta Med Iran. 2016 Jun;54(6):352-8. PMID: 27306340. |
| In vivo protocol: | 1. Uhl M, Aulwurm S, Wischhusen J, Weiler M, Ma JY, Almirez R, Mangadu R, Liu YW, Platten M, Herrlinger U, Murphy A, Wong DH, Wick W, Higgins LS, Weller M. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004 Nov 1;64(21):7954-61. doi: 10.1158/0008-5472.CAN-04-1013. PMID: 15520202. 2. Ge R, Rajeev V, Ray P, Lattime E, Rittling S, Medicherla S, Protter A, Murphy A, Chakravarty J, Dugar S, Schreiner G, Barnard N, Reiss M. Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo. Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4315-30. doi: 10.1158/1078-0432.CCR-06-0162. PMID: 16857807. |
1: Li M, Fang Y, Yao M, Yu WR, Ni T, Gu C, Yang PG, Mao ZG. [Effects of transforming growth factor β1 receptor inhibitor SD-208 on human hypertrophic scar]. Zhonghua Shao Shang Za Zhi. 2016 Jul 20;32(7):389-95. doi: 10.3760/cma.j.issn.1009-2587.2016.07.002. Chinese. PubMed PMID: 27464628.
2: Fadakar P, Akbari A, Ghassemi F, Mobini GR, Mohebi M, Bolhassani M, Abed Khojasteh H, Heidari M. Evaluation of SD-208, a TGF-β-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma. Acta Med Iran. 2016 Jun;54(6):352-8. PubMed PMID: 27306340.
3: Akbari A, Ghahremani MH, Mobini GR, Abastabar M, Akhtari J, Bolhassani M, Heidari M. Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor (SD-208). Iran J Basic Med Sci. 2015 Sep;18(9):856-61. PubMed PMID: 26523217; PubMed Central PMCID: PMC4620183.
4: Tandon M, Salamoun JM, Carder EJ, Farber E, Xu S, Deng F, Tang H, Wipf P, Wang QJ. SD-208, a novel protein kinase D inhibitor, blocks prostate cancer cell proliferation and tumor growth in vivo by inducing G2/M cell cycle arrest. PLoS One. 2015 Mar 6;10(3):e0119346. doi: 10.1371/journal.pone.0119346. eCollection 2015. PubMed PMID: 25747583; PubMed Central PMCID: PMC4352033.
5: Akbari A, Amanpour S, Muhammadnejad S, Ghahremani MH, Ghaffari SH, Dehpour AR, Mobini GR, Shidfar F, Abastabar M, Khoshzaban A, Faghihloo E, Karimi A, Heidari M. Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma. Daru. 2014 Jun 5;22:47. doi: 10.1186/2008-2231-22-47. PubMed PMID: 24902843; PubMed Central PMCID: PMC4077684.
6: Sun Y, Ye P, Wu J, Liu Z, Zhang A, Ren L, Cheng C, Huang X, Wang K, Deng P, Wu C, Yue Z, Xia J. Inhibition of intimal hyperplasia in murine aortic allografts by the oral administration of the transforming growth factor-beta receptor I kinase inhibitor SD-208. J Heart Lung Transplant. 2014 Jun;33(6):654-61. doi: 10.1016/j.healun.2014.02.020. Epub 2014 Feb 21. PubMed PMID: 24685405.
7: Mohammad KS, Javelaud D, Fournier PG, Niewolna M, McKenna CR, Peng XH, Duong V, Dunn LK, Mauviel A, Guise TA. TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res. 2011 Jan 1;71(1):175-84. doi: 10.1158/0008-5472.CAN-10-2651. Epub 2010 Nov 16. Erratum in: Cancer Res. 2011 Mar 1;71(5):2023. PubMed PMID: 21084275; PubMed Central PMCID: PMC3225124.
8: Leung SY, Niimi A, Noble A, Oates T, Williams AS, Medicherla S, Protter AA, Chung KF. Effect of transforming growth factor-beta receptor I kinase inhibitor 2,4-disubstituted pteridine (SD-208) in chronic allergic airway inflammation and remodeling. J Pharmacol Exp Ther. 2006 Nov;319(2):586-94. Epub 2006 Aug 3. PubMed PMID: 16888081.
9: Uhl M, Aulwurm S, Wischhusen J, Weiler M, Ma JY, Almirez R, Mangadu R, Liu YW, Platten M, Herrlinger U, Murphy A, Wong DH, Wick W, Higgins LS, Weller M. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004 Nov 1;64(21):7954-61. PubMed PMID: 15520202.
