XL147 analogue

Catalog No.S1118

XL147 analogue is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39 nM/36 nM/23 nM in cell-free assays, less potent to PI3Kβ. Phase 1/2.

Price Stock Quantity  
USD 170 In stock
USD 470 In stock
USD 770 In stock
USD 997 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

XL147 analogue Chemical Structure

XL147 analogue Chemical Structure
Molecular Weight: 448.52

Validation & Quality Control

2 customer reviews :

Quality Control & MSDS

Related Compound Libraries

XL147 analogue is available in the following compound libraries:

PI3K Inhibitors with Unique Features

Product Information

  • Compare PI3K
    Compare PI3K Products
  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

Description XL147 analogue is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39 nM/36 nM/23 nM in cell-free assays, less potent to PI3Kβ. Phase 1/2.
Targets PI3Kγ [1]
(Cell-free assay)
PI3Kδ [1]
(Cell-free assay)
PI3Kα [1]
(Cell-free assay)
PI3Kβ [1]
(Cell-free assay)

 View  More

IC50 23 nM 36 nM 39 nM 383 nM
In vitro XL147 inhibits class I PI3K isoforms in an ATP-competitive manner. In a panel of HER2-overexpressing human breast cancer cell lines, treatment with XL147 abrogates AKT and S6 phosphorylation but also induces the expression and phosphorylation of HER3 and other RTKs. In HER2+ cells, phosphorylation of HER3 is maintained by the HER2 tyrosine kinase, leading to partial recovery of phosphorylated AKT (pAKT) and thereby limiting the antitumor action of XL 147. In addition, knockdown of HER3 or treatment with the anti-HER2 agents trastuzumab or lapatinib sensitizes HER2+ breast cancer cells to XL147 in vitro and in vivo. Treatment with XL147 inhibits the monolayer growth of all tested cell lines, including BT474, HCC1937 et al. in a dose-dependent manner. The main effect of XL147 is inhibition of cell proliferation. XL147 induces cell death at the concentration of 20 μM. Treatment with XL147 leads to dose-dependent inhibition of PI3K. Consistent with the inhibition of cell proliferation, XL147 induces a reduction in cyclin D1 and pRB and an increase in levels of the CDK inhibitor p27KIPI but no detectable change in levels off total or cleaved poly (ADP-ribose) polymerase (PARP). Treatment with XL147 leads to a dose-dependent reduction in pAKTS473/T308 and pS6S240/244. Surprisingly, XL147 also triggers up-regulation of total HER3 and/or pHER3Y1289 levels. In HER2-overexpressing cells, inhibition of PI3K is followed by up-regulation of expression and phosphorylation of multiple receptor tyrosine kinases, including HER3. Knockdown of FoxO1 and FoxO3a transcription factors prevents the induction of HER3, InsR, IGF1R, and FGFR2 mRNAs upon inhibition of PI3K. In HER2+ cells, knockdown of HER3 with siRNA or cotreatment with the HER2 inhibitors trastuzumab or lapatinib enhances XL147-induced cell death and inhibition of pAKT and pS6. [2]
In vivo Athymic mice with BT474 xenografts are randomly treated with XL147, lapatinib, trastuzumab, or XL147 plus each HER2 antagonist. Each monotherapy significantly inhibtis tumor growth with trastuzumab being the only agent that induced a complete tumor regression in one of eight mice. Both combinations are superior to the respective drugs given alone. Notably, the combination of trastuzumab and XL147, but not lapatinib and XL147, induces a complete tumor response in three of eight mice. There is no marked drug-related toxicity in any of the treatment arms. The combination of XL147 plus trastuzumab prevents pHER3 more potently than any of the other treatments. In good agreement with differences in tumor growth among treatment arms, nuclear pAKT is lower in tumors treated with XL147 plus lapatinib or XL147 plus trastuzumab compared with tumors treated with single agents. Of all three single drugs, XL147 is the only one shown statistically to repress nuclear pAKT levels. There are no detectable changes in cytoplasmic pAKT levels. Combined inhibition of HER2 and PI3K in HER2-dependent xenografts is required to maximally inhibit signaling output of the PI3K/AKT pathway. [2]
Features

Protocol(Only for Reference)

Cell Assay:

[2]

Cell lines BT474 and HCC1937 cells
Concentrations 0-20 μM
Incubation Time 72 hours
Method

Cells including BT474, HCC1937 et al. are seeded in 100-mm dishes in media containing 2.5% FBS with or without XL147. After 3 days, detached and adherent cells are pooled, fixed, and labeled with propidium iodide by using the APO-BrdU kit. Labeled cells are analyzed using the Becton Dickinson FACSCalibur system.

Animal Study:

[2]

Animal Models Athymic female mouse bearing BT474 cells
Formulation Formulated in 10 mM HCl, in sterile water for injection
Dosages 100 mg/kg
Administration Orogastric gavage

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] 2010 ASCO Annual Meeting

[2] Chakrabarty A, et al. Proc Natl Acad Sci U S A, 2011, 1-6.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-06-25)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01943838 Completed Neoplasm Malignant Sanofi October 2013 Phase 1
NCT01587040 Active, not recruiting Neoplasm Malignant Sanofi July 2012 Phase 1|Phase 2
NCT01436565 Completed Solid Tumor Cancers Sanofi|Merrimack Pharmaceuticals November 2011 Phase 1
NCT01392924 Completed Neoplasm Malignant Sanofi August 2011 Phase 1
NCT01357330 Completed Solid Tumors Sanofi May 2011 Phase 1

view more

Chemical Information

Download XL147 analogue SDF
Molecular Weight (MW) 448.52
Formula

C21H16N6O2S2

CAS No. 956958-53-5
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms SAR245408
Solubility (25°C) * In vitro DMSO 3 mg/mL (6.68 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 15 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.
Chemical Name N-(3-(benzo[c][1,2,5]thiadiazol-5-ylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

Customer Product Validation(2)


Click to enlarge
Rating
Source XL147 analogue purchased from Selleck
Method Western blot
Cell Lines Breast cancer cells
Concentrations 0.1-20 μM
Incubation Time 24 h
Results

Click to enlarge
Rating
Source Dr. Chunrong Yu of RoswelI Park Cancer Institute. XL147 analogue purchased from Selleck
Method Western blot analysis
Cell Lines
Concentrations 0-15 μM
Incubation Time
Results XL147 treatment resulted in a reduction of AKT phosphorylation.

Tech Support

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.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related PI3K Products

  • GDC-0032

    GDC-0032 is a potent, next-generation β isoform-sparing PI3K inhibitor targeting PI3Kα/δ/γ with Ki of 0.29 nM/0.12 nM/0.97nM, >10 fold selective over PI3Kβ.

    Features:A beta isoform-sparing PI3K inhibitor.

  • Pilaralisib (XL147)

    Pilaralisib (XL147) is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39 nM/36 nM/23 nM in cell-free assays, less potent to PI3Kβ. Phase 1/2.

  • GNE-317

    GNE-317 is a potent, brain-penetrant PI3K inhibitor.

  • LY294002

    LY294002 is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM in cell-free assays, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation.

  • 3-Methyladenine (3-MA)

    3-Methyladenine (3-MA) is a selective PI3K inhibitor for Vps34 and PI3Kγ with IC50 of 25 μM and 60 μM in HeLa cells; blocks class I PI3K consistently, whereas suppression of class III PI3K is transient, and also blocks autophagosome formation.

  • CAL-101 (Idelalisib, GS-1101)

    CAL-101 (Idelalisib, GS-1101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR.

  • Wortmannin

    Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Also blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays.

  • BEZ235 (NVP-BEZ235, Dactolisib)

    BEZ235 (NVP-BEZ235, Dactolisib) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell.

  • BKM120 (NVP-BKM120, Buparlisib)

    BKM120 (NVP-BKM120, Buparlisib) is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Phase 2.

  • Pictilisib (GDC-0941)

    Pictilisib (GDC-0941) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Phase 2.

Recently Viewed Items

Tags: buy XL147 analogue | XL147 analogue supplier | purchase XL147 analogue | XL147 analogue cost | XL147 analogue manufacturer | order XL147 analogue | XL147 analogue distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us