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XL765 (SAR245409)

XL765 is a dual inhibitor of mTOR/PI3k for mTOR, p110α, p110β, p110γ and p110δ with IC50 of 157 nM, 39 nM, 113 nM, 9 nM and 43 nM, respectively.

Catalog No.S1523

3 Reviews 1 Product Citations

: Tel: +1-832-582-8158[email protected]

XL765 (SAR245409) Chemical Structure
Molecular Weight: 599.66

Validation & Quality Control

Product Citations(1)

Endocrinology, 2013, 154(3):1247-59

Customer Reviews(3) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

XL765 (SAR245409) is available in the following compound libraries:

Inhibitor Library (96-well) Kinase Inhibitor Library (96-well) Chemical Library (96-well)

Product Information

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Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S1009	BEZ235 (NVP-BEZ235)	<1 mg/mL	1 mg/mL	<1 mg/mL
S1105	LY294002	<1 mg/mL	36 mg/mL	21 mg/mL
S1065	GDC-0941	<1 mg/mL	44 mg/mL	<1 mg/mL
S2226	CAL-101 (GS-1101)	<1 mg/mL	83 mg/mL	35 mg/mL
S2247	BKM120 (NVP-BKM120)	<1 mg/mL	82 mg/mL	2 mg/mL
S2638	NU7441 (KU-57788)	<1 mg/mL	3 mg/mL	<1 mg/mL
S2814	BYL719	<1 mg/mL	88 mg/mL	5 mg/mL
S1038	PI-103	<1 mg/mL	24 mg/mL	<1 mg/mL
S1169	TGX-221	<1 mg/mL	12 mg/mL	<1 mg/mL
S2758	Wortmannin	<1 mg/mL	86 mg/mL	<1 mg/mL
S2636	A66	<1 mg/mL	79 mg/mL	1 mg/mL
S1072	ZSTK474	<1 mg/mL	21 mg/mL	<1 mg/mL
S1118	XL147	<1 mg/mL	3 mg/mL	<1 mg/mL
S2767	3-Methyladenine	<1 mg/mL	4 mg/mL	4 mg/mL
S1268	IC-87114	<1 mg/mL	0.66 mg/mL	<1 mg/mL
S1410	AS-605240	<1 mg/mL	0.4 mg/mL	<1 mg/mL
S2671	AS-252424	<1 mg/mL	61 mg/mL	<1 mg/mL
S1523	XL765 (SAR245409)	<1 mg/mL	15 mg/mL	<1 mg/mL
S2658	GSK2126458	<1 mg/mL	101 mg/mL	<1 mg/mL
S1205	PIK-75	<1 mg/mL	3 mg/mL	<1 mg/mL
S2743	PF-04691502	<1 mg/mL	14 mg/mL	<1 mg/mL
S1462	AZD6482	<1 mg/mL	82 mg/mL	28 mg/mL
S2628	PF-05212384 (PKI-587)	<1 mg/mL	2 mg/mL	<1 mg/mL
S2696	GDC-0980 (RG7422)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1489	PIK-93	<1 mg/mL	78 mg/mL	<1 mg/mL
S1187	PIK-90	<1 mg/mL	0.28 mg/mL	<1 mg/mL
S2802	BAY80-6946	0.002 mg/mL	0.002 mg/mL	0.01 mg/mL
S1352	TG100-115	<1 mg/mL	9 mg/mL	<1 mg/mL
S1219	YM201636	<1 mg/mL	35 mg/mL	<1 mg/mL
S1360	GSK1059615	<1 mg/mL	2 mg/mL	<1 mg/mL
S2227	PIK-294	<1 mg/mL	98 mg/mL	<1 mg/mL
S2681	AS-604850	<1 mg/mL	57 mg/mL	5 mg/mL
S2699	CH5132799	<1 mg/mL	12 mg/mL	<1 mg/mL
S2682	CAY10505	<1 mg/mL	58 mg/mL	<1 mg/mL
S2749	NVP-BGT226	<1 mg/mL	30 mg/mL	<1 mg/mL
S2759	PI3K/HDAC InhibitorⅠ	<1 mg/mL	102 mg/mL	<1 mg/mL
S2207	PIK-293	<1 mg/mL	80 mg/mL	<1 mg/mL
S2739	PKI-402	<1 mg/mL	0.4 mg/mL	<1 mg/mL
S2870	TG 100713	<1 mg/mL	2 mg/mL	<1 mg/mL
S8002	GSK2636771	<1 mg/mL	87 mg/mL	19 mg/mL
S7028	IPI-145 (INK1197)	<1 mg/mL	84 mg/mL	<1 mg/mL

Research Area
Research Area
Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	XL765 is a dual inhibitor of mTOR/PI3k for mTOR, p110α, p110β, p110γ and p110δ with IC50 of 157 nM, 39 nM, 113 nM, 9 nM and 43 nM, respectively.
Targets	mTOR	p110α	p110β	p110γ	p110δ
IC50	157 nM	39 nM	113 nM	9 nM	43 nM ^[1]
In vitro	XL765 is active against class I PI3K (IC50 = 39, 113, 9 and 43 nM for p110α, β, γ and δ, respectively). XL765 also inhibits DNA-PK (IC50 = 150 nM) and mTOR (IC50 = 157 nM) but not XL-147 which shows IC50 values of > 15 μM. ^[1] XL765 treatment results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. XL765, a dual-target PI3K/mTOR inhibitor, inhibits cell growth and apoptosis in many more cell lines and at lower concentrations as compared to the PI3K-selective inhibitors XL147 and PIK90. The effect can be recapitulated by using combinations of single-targeted compounds. XL765 significantly reduces phosphorylation of the mTOR targets S6, S6K, and 4EBP1, which is associated with greater apoptosis induction rather than to PI3K inhibition alone. XL765 treatment causes accumulation of autophagosomes in MIAPaCa-2 cells, and results in significant dose-dependent AVO induction and LC3-II stimulation in MIAPaCa-2 cells stably expressing a LC3-GFP construct. ^[2]
In vivo	The combination of XL765 (30 mg/kg) with chloroquine (50 mg/kg) results in significant inhibition of BxPC-3 xenograft growth in mice models, while XL765 alone at the same dose has no inhibitory effect. ^[2] Oral administration of XL765 results in greater than 12-fold reduction in median tumor bioluminescence compared to control and improvement in median survival in nude mice implanted intracranially with GBM 39-luc cells. XL765 in combination with temozolomide (TMZ) yields a 140-fold reduction in median bioluminescence with a trend toward improvement in median survival compared with TMZ alone. ^[3]
Clinical Trials	A Phase I study to evaluate the safety and tolerability of XL765 in combination with erlotinib in subjects with solid tumors has been completed.
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[2]

Cell lines	Pancreatic cancer cell lines (HcG25, Panc89, PA-TU8988T, Panc2.13, MiaPaCa2, Panc10.05, Panc8.13, BxPC-3, etc.)
Concentrations	Dissolved in DMSO, final concentration ~10 μM
Incubation Time	24, 48, 72 hours
Method	Cells are treated with XL765 24 hours after plating and harvested for apoptosis or autophagy assays at 24, 48, or 72 hours after XL765 treatment. Apoptosis is determined by total percentage of annexin V-positive cells by fluorescence-activated cell sorting (FACS). Acidic vesicular organelles (AVOs) are detected in XL765-treated cells by vital staining with acridine orange. The degree of AVO formation is expressed as fold increase of acridine orange fluorescence intensity (FL3) in XL765-treated cells versus control cells.

Animal Study: ^[2]

Animal Models	Female Nu/Nu mice inoculated s.c. with BxPC-3 cells
Formulation	Solubilized in water/10 mM HCl
Dosages	30 mg/kg
Administration	Oral gavage once a day

References

Chemical Information

Download XL765 (SAR245409) SDF

Molecular Weight (MW)	599.66
Formula	C₃₁H₂₉N₅O₆S
CAS No.	1349796-36-6
Synonyms	N/A

Solubility (25°C) DMSO 15 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	Benzamide, N-[4-[[[3-[(3,5-dimethoxyphenyl)amino]-2-quinoxalinyl]amino]sulfonyl]phenyl]-3-methoxy-4-methyl-

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Research Area

Customer Reviews (3)

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Rating

Source

Endocrinology, 2013, 154(3), 1247-59. XL765 (SAR245409) purchased from Selleck

Method

Serum GH and PRL secretion assay

Cell Lines

female nude mice

Concentrations

25 mg/kg

Incubation Time

Results

The TMZ/XL765 combination decreased both serum rat-GH and rat-PRL dramatically compared with either agent alone.

Click to enlarge

Rating

Source

Endocrinology, 2013, 154(3), 1247-59. XL765 (SAR245409) purchased from Selleck

Method

TUNEL staining

Cell Lines

GH3 cells

Concentrations

25 mg/kg

Incubation Time

Results

TMZ (5 mg/kg) or XL765 (25 mg/kg) alone moderately decreased the number of Ki-67-positive cells (Figure A and B) and increased the number of TUNEL-positive cells (Figure C and D) compared with the DMSO-treated tumors. However, the TMZ/XL765 combination dramatically increased the number of TUNEL-positive cells and decreased the number of Ki-67-positivecells compared with either agent alone.

Click to enlarge

Rating

Source

Dr. Zhang of Tianjin Medical University. XL765 (SAR245409) purchased from Selleck

Method

Western blot

Cell Lines

A549 cells

Concentrations

0-1 μM

Incubation Time

3 h

Results

XL765 treatment resulted in a reduction of Akt phosphorylation in A549 cells.

Product Citations (1)

Inhibition of PI3K/AKT/mTOR Pathway Enhances Temozolomide-Induced Cytotoxicity in Pituitary Adenoma Cell Lines in Vitro and Xenografted Pituitary Adenoma in Female Nude Mice. [Dai C, et al. Endocrinology 2013;154(3):1247-59]
PubMed: 23384836

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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BEZ235 (NVP-BEZ235)

BEZ235 (NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor of p110α, p110γ, p110δ and p110β with IC50 of 4 nM, 5 nM, 7 nM and 75 nM, respectively, and also inhibits ATR with IC50 of 21 nM.
Deforolimus (Ridaforolimus)

Deforolimus (Ridaforolimus, AP23573, MK-8669) is a selective mTOR inhibitor with IC50 of 0.2 nM.
PI-103

PI-103 is a potent, ATP-competitive PI3K inhibitor of DNA-PK, p110α, mTORC1, PI3KC2β, p110δ, mTORC2, p110β, and p110γ with IC50 of 2 nM, 8 nM, 20 nM, 26 nM, 48 nM, 83 nM, 88 nM and 150 nM, respectively.
GDC-0941

GDC-0941 is a potent inhibitor of PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ with IC50 of 3 nM, 33 nM, 3 nM and 75 nM, respectively.
ZSTK474

ZSTK474 is a potent pan-class I PI3K inhibitor with IC50 of 37 nM.
LY294002

LY294002 is a PI3K inhibitor for p110α, p110δ and p110β with IC50 of 0.5 μM, 0.57 μM and 0.97 μM, respectively.
XL147

XL147 (SAR245408) is a selective and reversible class I PI3K inhibitor for wild type and mutant p110α with IC50 of 40 nM and 40 nM, respectively.
TGX-221

TGX-221 is a potent, selective PI3K inhibitor for p110β with IC50 of 8.5 nM.
PIK-90

PIK-90 is a potent and cell permeable inhibitor of p110α, p110β, p110γ and p110δ with IC50 of 11 nM, 350 nM, 18 nM and 58 nM, respectively.
PIK-75

PIK-75 is a selective and competitive inhibitor of p110α with IC50 of 5.8 nM and also potently inhibits DNA-PK with IC50 of 2 nM.

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XL765 (SAR245409)