SB-590885 | CAS#405554-55-4 | Raf inhibitor

MedKoo Cat#: 406109 | Name: SB-590885

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Description:

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

SB-590885 is a novel triarylimidazole that selectively inhibits Raf kinases with more potency towards B-Raf than c-Raf. SB-590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration, which is distinct from the previously reported mechanism of action of the multi-kinase inhibitor, BAY43-9006. Malignant cells expressing oncogenic B-Raf show selective inhibition of mitogen-activated protein kinase activation, proliferation, transformation, and tumorigenicity when exposed to SB-590885 , whereas other cancer cell lines and normal cells display variable sensitivities or resistance to similar treatment.

Chemical Structure

SB-590885

CAS#40554-55-4

Theoretical Analysis

MedKoo Cat#: 406109

Name: SB-590885

CAS#: 40554-55-4

Chemical Formula: C27H27N5O2

Exact Mass: 453.2165

Molecular Weight: 453.54

Elemental Analysis: C, 71.50; H, 6.00; N, 15.44; O, 7.06

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,350.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Synonym

SB590885; SB590885; SB 590885

IUPAC/Chemical Name

(E)-5-(2-(4-(2-(dimethylamino)ethoxy)phenyl)-5-(pyridin-4-yl)-1H-imidazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime

InChi Key

MLSAQOINCGAULQ-QFMPWRQOSA-N

InChi Code

InChI=1S/C27H27N5O2/c1-32(2)15-16-34-22-7-3-19(4-8-22)27-29-25(18-11-13-28-14-12-18)26(30-27)21-5-9-23-20(17-21)6-10-24(23)31-33/h3-5,7-9,11-14,17,33H,6,10,15-16H2,1-2H3,(H,29,30)/b31-24+

SMILES Code

CN(CCOC1=CC=C(C2=NC(C3=CC4=C(/C(CC4)=N/O)C=C3)=C(C5=CC=NC=C5)N2)C=C1)C

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, DMF, and ethanol

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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SB-590885 is a potent B-Raf inhibitor (Kd = 0.3 nM). It less effectively inhibits c-Raf (Ki = 1.72 nM) and has little effect at 46 other kinases. SB-590885 blocks activation of ERK1/2 and anchorage-independent cell proliferation of melanoma cells with either wild type or V600E B-Raf at nanomolar concentrations.

In vitro activity:

In the study, SB-590885 was observed to stabilize the oncogenic B-Raf kinase domain in an active state. Cells expressing oncogenic B-Raf displayed a specific response to SB-590885, inhibiting mitogen-activated protein kinase activation, proliferation, transformation, and tumorigenicity. While these effects were notable in malignant cells expressing oncogenic B-Raf, varying responses were observed in other cancer cell lines and normal cells upon similar treatment. Reference: Cancer Res. 2006 Dec 1;66(23):11100-5. https://pubmed.ncbi.nlm.nih.gov/17145850/

In vivo activity:

When applied to human cerebral arteries in a cultured environment, SB-590885 significantly reduced the contractions mediated by 5-HT₁(B), AT₁, and ET(B) receptors and also led to a substantial reduction in AT₁ receptor immunoreactivity. SB-590885 mitigated the increase in phosphorylated B-Raf expression induced during the culture process. Reference: BMC Neurosci. 2011 Jan 11;12:5. https://pubmed.ncbi.nlm.nih.gov/21223556/

	Solvent	mg/mL	mM
Solubility
	DMF	2.0	4.41
	DMSO	3.0	6.62
	Ethanol	0.5	1.10

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 453.54 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. Aldaghi SA, Jalal R. Concentration-Dependent Dual Effects of Ciprofloxacin on SB-590885-Resistant BRAFV600E A375 Melanoma Cells. Chem Res Toxicol. 2019 Apr 15;32(4):645-658. doi: 10.1021/acs.chemrestox.8b00335. Epub 2019 Mar 14. PMID: 30829029. 2. King AJ, Patrick DR, Batorsky RS, Ho ML, Do HT, Zhang SY, Kumar R, Rusnak DW, Takle AK, Wilson DM, Hugger E, Wang L, Karreth F, Lougheed JC, Lee J, Chau D, Stout TJ, May EW, Rominger CM, Schaber MD, Luo L, Lakdawala AS, Adams JL, Contractor RG, Smalley KS, Herlyn M, Morrissey MM, Tuveson DA, Huang PS. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res. 2006 Dec 1;66(23):11100-5. doi: 10.1158/0008-5472.CAN-06-2554. PMID: 17145850. 3. Ahnstedt H, Säveland H, Nilsson O, Edvinsson L. Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway. BMC Neurosci. 2011 Jan 11;12:5. doi: 10.1186/1471-2202-12-5. PMID: 21223556; PMCID: PMC3023719.

In vitro protocol:

In vivo protocol:

1. Ahnstedt H, Säveland H, Nilsson O, Edvinsson L. Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway. BMC Neurosci. 2011 Jan 11;12:5. doi: 10.1186/1471-2202-12-5. PMID: 21223556; PMCID: PMC3023719.

1: Wang X, Salaski EJ, Berger DM, Powell D, Hu Y, Wojciechowicz D, Collins K, Frommer E. Structure-based design of isoindoline-1,3-diones and 2,3-dihydrophthalazine-1,4-diones as novel B-Raf inhibitors. Bioorg Med Chem Lett. 2011 Dec 1;21(23):6941-4. doi: 10.1016/j.bmcl.2011.10.012. Epub 2011 Oct 12. PubMed PMID: 22024030. 2: Klein RM, Higgins PJ. A switch in RND3-RHOA signaling is critical for melanoma cell invasion following mutant-BRAF inhibition. Mol Cancer. 2011 Sep 14;10:114. doi: 10.1186/1476-4598-10-114. PubMed PMID: 21917148; PubMed Central PMCID: PMC3180434. 3: Park H, Choi H, Hong S, Hong S. Identification of novel BRAF kinase inhibitors with structure-based virtual screening. Bioorg Med Chem Lett. 2011 Oct 1;21(19):5753-6. doi: 10.1016/j.bmcl.2011.08.010. Epub 2011 Aug 8. PubMed PMID: 21873050. 4: Ahnstedt H, SÃ¤veland H, Nilsson O, Edvinsson L. Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway. BMC Neurosci. 2011 Jan 11;12:5. doi: 10.1186/1471-2202-12-5. PubMed PMID: 21223556; PubMed Central PMCID: PMC3023719. 5: Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubbenhorst B, Xu X, Gimotty PA, Kee D, Santiago-Walker AE, Letrero R, D'Andrea K, Pushparajan A, Hayden JE, Brown KD, Laquerre S, McArthur GA, Sosman JA, Nathanson KL, Herlyn M. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010 Dec 14;18(6):683-95. doi: 10.1016/j.ccr.2010.11.023. PubMed PMID: 21156289; PubMed Central PMCID: PMC3026446. 6: Smalley KS, Lioni M, Dalla Palma M, Xiao M, Desai B, Egyhazi S, Hansson J, Wu H, King AJ, Van Belle P, Elder DE, Flaherty KT, Herlyn M, Nathanson KL. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol Cancer Ther. 2008 Sep;7(9):2876-83. doi: 10.1158/1535-7163.MCT-08-0431. PubMed PMID: 18790768; PubMed Central PMCID: PMC2651569. 7: Takle AK, Bamford MJ, Davies S, Davis RP, Dean DK, Gaiba A, Irving EA, King FD, Naylor A, Parr CA, Ray AM, Reith AD, Smith BB, Staton PC, Steadman JG, Stean TO, Wilson DM. The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4373-6. doi: 10.1016/j.bmcl.2008.06.070. Epub 2008 Jun 24. PubMed PMID: 18621524. 8: Senawong T, Phuchareon J, Ohara O, McCormick F, Rauen KA, Tetsu O. Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options. Hum Mol Genet. 2008 Feb 1;17(3):419-30. Epub 2007 Nov 2. PubMed PMID: 17981815. 9: Li N, Batt D, Warmuth M. B-Raf kinase inhibitors for cancer treatment. Curr Opin Investig Drugs. 2007 Jun;8(6):452-6. Review. PubMed PMID: 17621874. 10: King AJ, Patrick DR, Batorsky RS, Ho ML, Do HT, Zhang SY, Kumar R, Rusnak DW, Takle AK, Wilson DM, Hugger E, Wang L, Karreth F, Lougheed JC, Lee J, Chau D, Stout TJ, May EW, Rominger CM, Schaber MD, Luo L, Lakdawala AS, Adams JL, Contractor RG, Smalley KS, Herlyn M, Morrissey MM, Tuveson DA, Huang PS. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res. 2006 Dec 1;66(23):11100-5. PubMed PMID: 17145850. 11: Takle AK, Brown MJ, Davies S, Dean DK, Francis G, Gaiba A, Hird AW, King FD, Lovell PJ, Naylor A, Reith AD, Steadman JG, Wilson DM. The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81. Epub 2005 Nov 2. PubMed PMID: 16260133.