AZ 628

貨號 Cat. No.: S2746
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Description

AZ 628

Catalog No.S27461 Product Citations

AZ628 is a new pan-Raf inhibitor for BRAF, BRAFV600E, and c-Raf-1 with IC50 of 105 nM, 34 nM and 29 nM, also inhibits VEGFR2, DDR2, Lyn, Flt1, FMS, etc.

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Price

Stock

Quantity

10mM/1mLIn DMSO	USD 340	In stock	0 1 2 3 4 5 6 7 8 9 10
5mg	USD 189	In stock	0 1 2 3 4 5 6 7 8 9 10
25mg	USD 592	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	AZ628 is a new pan-Raf inhibitor for BRAF, BRAFV600E, and c-Raf-1 with IC50 of 105 nM, 34 nM and 29 nM, also inhibits VEGFR2, DDR2, Lyn, Flt1, FMS, etc.
Targets	wild-type CRAF	BRAF^V600E	wild-type BRAF
IC50	29 nM	34 nM	100 nM ^[1]
In vitro	AZ628 prevents activation of number of tyrosine protein kinases including VEGFR2, DDR2, Lyn, Flt1, FMS and others. AZ628 suppresses anchorage-dependent and -independent growth, gives rise to cell cycle arrest, and induces apoptosis in colon and melanoma cell lines harboring B-RafV600E mutation. The profile of AZ628 cross-reactivity suggests that similar to sorafenib, AZ628 may be antiangiogenic based on prevention of VEGFR2. ^[1] AZ628-resistant clones are approximately 100-fold more resistant to AZ628 than the parental cell line, exhibiting IC50 of approximately 10 μM, compared with 0.1 μM for the parental cell line. Effective suppression of p-ERK1/2 levels is observed in the M14 parental cell line following treatment with increasing concentrations of AZ628. AZ628-resistant clones express elevated CRAF. Elevated CRAF expression is a potential mechanism of acquired resistance to continuous AZ628 exposure, resulting in sustained activation of ERK1/2. p-ERK1/2 activity is not significantly inhibited by exposure to AZ628 in one of these three AZ628-insensitive cell lines (Wm1552C). Unlike in the AZ628-resistant M14 cells in which AZ628 fails to suppress the activation of ERK, AZ628 treatment efficiently attenuates ERK activation in the NRAS mutant melanoma cells.^[2]
In vivo
Features

Protocol(Only for Reference)

Cell Assay: ^[1]

Cell lines	M14 expressing the V600E BRAF mutation
Concentrations	0.01-10 μM
Incubation Time	Overnight
Method	Approximately 0.5-2.5 × 10⁵ M14 cells are seeded in 12 or 24 - well plates, respectively, in medium supplemented with 5% FBS. After overnight incubation, the cells are treated with various concentrations of AZ628. Fresh medium and drug is replaced every 2 days until the untreated control wells reached confluence. At this time-point, the media is removed and the cells are fixed in 4% formaldehyde in PBS for 20 minutes at room temperature. Cells are then washed twice with PBS and stained with a 1:5000 solution of the fluorescent nucleic acid stain Syto60. Quantitation of fluorescent signal intensity is carried out at 700 nm, using an Odyssey Infrared Imager. Each experiment is performed in quadruplicate and the results shown represent the average of the four values compared to untreated wells. Error bars represent standard deviation of the 4 values from the mean. High-throughput cell growth/viability assays are performed.

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01592747	Completed	Autism Spectrum Disorder (ASD)\|Autism\|Autistic Disorder\|Asperger’s Disorder\|Asperger’s\|Pediatric Autism\|Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)\|Pervasive Child Development D	Forest Laboratories	2012-09	Phase 2
NCT01592773	Active, not recruiting	Autism Spectrum Disorder (ASD)\|Autism\|Autistic Disorder\|Asperger’s Disorder\|Asperger’s\|Pediatric Autism\|Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)\|Pervasive Child Development D	Forest Laboratories	2012-09	Phase 2
NCT01665053	Active, not recruiting	Coronary Artery Disease	Boston Scientific Corporation	2012-11	Phase 3
NCT01764633	Recruiting	Dyslipidemia	Amgen	2013-01	Phase 3
NCT01870778	Recruiting	Acute Heart Failure	Novartis\|Novartis Pharmaceuticals	2013-10	Phase 3

Chemical Information

Download AZ 628 SDF

Molecular Weight (MW)	451.52
Formula	C₂₇H₂₅N₅O₂
CAS No.	878739-06-1

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	N/A

Solubility (25°C) *	In vitro	DMSO	90 mg/mL (199 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
	In vivo	30% PEG400/0.5% Tween80/5% propylene glycol,	30 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.