AP26113

貨號 Cat. No.: S7000
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Description

AP26113

Catalog No.S7000

AP26113 is a potent ALK inhibitor with IC50 of 0.62 nM, demonstrated ability overcome Crizotinib resistance mediated by a L1196M mutation. Phase 1/2.

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Price

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Quantity

10mM/1mLIn DMSO	USD 370	In stock	0 1 2 3 4 5 6 7 8 9 10
5mg	USD 264	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 466	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 1600	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	AP26113 is a potent ALK inhibitor with IC50 of 0.62 nM, demonstrated ability overcome Crizotinib resistance mediated by a L1196M mutation. Phase 1/2.
Targets	ALK	FER	ROS/ROS1	FLT3	FES/FPS
IC50	0.62 nM	1.3 nM	1.9 nM	2.1 nM	3.4 nM ^[1]
In vitro	AP26113 is highly active against both sensitive and resistant H3122 cells, decreasing cell growth, suppressing ALK phosphorylation and inducing apoptosis in a dose dependent manner. AP26113 decreases p-ALK in the H3122 and H3122 CR cells, with IC50 values of 7.4 versus 16.8 nM, respectively. AP26113 decreases cell number in Ba/F3 cells expressing either native or mutant EML4-ALK with IC50 of 10 nM and 24 nM, respectively.^[1] AP26113 inhibits cell growth of SU-DHL-1, H3122 and Ba/F3-EML4-ALK v1 cell lines with GI50 of 9 nM, 4 nM and 13 nM, respectively. AP26113 inhibits phosphorylation of ALK with IC50 of 3.2 nM, 1.5 nM and 2.1 nM in Karpas-299, SU-DHL-1 and L-82 cell lines. AP26113 dose-dependently inhibits phosphorylation of ALK and ERK in Karpas-299 and H3122 cells. ^[2] AP26113 inhibits cell growth with IC50 of 11 nM and 16 nM in Ba/F3 line (native EML4-ALK) and Ba/F3 line (EML4-ALK G1269S mutants). AP26113 inhibits ALK phosphorylationh with IC50 of 74 nM and 335 nM in Ba/F3 line (native EML4-ALK) and Ba/F3 line (EML4-ALK E1210K mutants). AP26113 (10 mg/kg-75 mg/kg) is efficacious in PF-02341066-resistant EML4-ALK mutant mouse xenograft models. AP26113 induces regression of tumors expressing native EML4-ALK and the G1269S and L1196M mutants at 25 mg/kg, 50 mg/kg and 50 mg/kg, respectively. ^[3] AP26113 inhibits EGFR phosphorylation and viability with IC50 of 75 nM and 114 nM, respectively, in Ba/F3 cells expressing EGFR-DEL. AP26113 inhibits EGFR phosphorylation and viability with IC50s of 15 and 281 nM, respectively, in Ba/F3 cells expressing EGFR-DEL/T790M. AP26113 inhibits EGFR phosphorylation with an IC50 of 62 nM and cell growth with a GI50 of 165 nM in a NSCLC line expressing EGFR-DEL (HCC827). AP26113 inhibits EGFR phosphorylation with an IC50 of 59 nM and cell growth with a GI50 of 245 nM in HCC827 cells expressing EGFR-DEL/T790M. AP26113 potently inhibits SLC34A2-ROS-driven signaling and proliferation in a dose dependent manner in HCC78 NSCLC cells.^[4]
In vivo	AP26113 (< 50 mg/kg) dose-dependently inhibits p-ALK in tumor of Karpas-299 xenograft mice model. AP26113 (< 50 mg/kg) dose-dependently inhibits tumor growth in Karpas-299 xenograft mice model and H3122 xenograft mice model. AP26113 demonstrates favorable properties including moderate in vitro plasma protein binding (47%, 70% and 76% in human, rat, mouse), negligible inhibition of major CYP isoforms. AP26113 (10 mg/kg) is well-tolerated with Cmax of 2587 ng/mL and AUC of 41120 hr.ng/mL in rats. ^[2]AP26113 (25 mg/kg) leads to tumor regression in HCC827(EGFR-DEL) or HCC827(EGFR-DEL/T790M) xenograft mice model. ^[4]
Features	At least 10-fold more potent and selective in ALK inhibition relative to crizotinib.

Protocol(Only for Reference)

Cell Assay: ^[2]

Cell lines	SU-DHL-1, H3122 and Ba/F3-EML4-ALK v1 cell lines
Concentrations	~1 μM
Incubation Time	72 hours
Method	Cell growth is assessed using either Cell Titer 96 Aqueous One Solution Cell Proliferation Assay or CyQuant Cell proliferation Assay. 24 hours after plating, cells are treated with AP26113 and grown for 72 hours. The concentration that causes 50% growth inhibition (GI50) is determined by correcting for the cell count at time zero (time of treatment) and plotting data as percent growth relative to vehicle (DMSO) treated cells using XLfit version 4.2.2 for Microsoft Excel.

Animal Study: ^[2]

Animal Models	Karpas-299 or H3122 xenograft mice model
Dosages	100 mg/kg
Administration	Orally
Solubility	NMP/polyethylene glycol 300 (10/90, v/v), 30 mg/mL

References

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

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01449461	Recruiting	Advanced Malignancies\|Carcinoma, Non-Small-Cell Lung\|Anaplastic Large Cell Lymphoma\|Diffuse Large Cell Lymphoma\|Inflammatory Myofibroblastic Tumors	Ariad Pharmaceuticals	2011-09	Phase 1\|Phase 2

Chemical Information

Download AP26113 SDF

Molecular Weight (MW)	529.01
Formula	C₂₆H₃₄ClN₆O₂P
CAS No.	1197958-12-5

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

Solubility (25°C) *	In vitro	DMSO	45 mg/mL (85 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	106 mg/mL (200 mM)
	In vivo	NMP/polyethylene glycol 300 (10/90, v/v),	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.