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GDC-0941PI3K inhibitor,potent and selective

GDC-0941

Catalog No. A8210
Size Price Stock Qty
10mM (in 1mL DMSO) $55.00 In stock
Evaluation Sample $28.00 In stock
10mg $50.00 In stock
50mg $75.00 In stock
200mg $210.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Product Citations

1. Sabha N, Volpatti JR, et al. "PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models." J Clin Invest. 2016 Sep 1;126(9):3613-25. PMID:27548528
2.Lindblad, Oscar, et al. "PI3 kinase is indispensable for oncogenic transformation by the V560D mutant of c-Kit in a kinase-independent manner." Cellular and Molecular Life Sciences (2015): 1-9. PMID:26040420
3.Pittini Á, Casaravilla C, et al. "Pharmacological inhibition of PI3K class III enhances the production of pro- and anti-inflammatory cytokines in dendritic cells stimulated by TLR agonists." Int Immunopharmacol. 2016 May 8;36:213-217. PMID:27168056
4.Tsioumpekou M, Papadopoulos N, et al."Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling." Cell Signal. 2016 Jun 21;28(9):1422-1431. PMID:27168056

Quality Control

Chemical structure

GDC-0941

Related Biological Data

GDC-0941
GDC-0941 inhibits PI3K signaling in drug-sensitive U87 tumors. Western blotting data for expression of pAKT, tAKT, pGSK-3β & tGSK-3β in U87. Data are representative of 4 independent mice dosed with vehicle or 50 mg/kg GDC-0941 twice daily for 8 days and were normalized to β-actin.

Related Biological Data

GDC-0941

Related Biological Data

GDC-0941

Related Biological Data

GDC-0941

Related Biological Data

GDC-0941

Related Biological Data

GDC-0941

Related Biological Data

GDC-0941

Biological Activity

Description GDC-0941 is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).
Targets PI3Kα PI3Kβ PI3Kδ PI3Kγ    
IC50 3 nM 33 nM 3 nM 75 nM    

Protocol

Cell experiment [1]:

Cell lines

Trastuzumab-Sensitive and -Insensitive HER2-Amplified Cells

Preparation method

Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

2 h

Applications

250 nM GDC-0941 treatment for 2 hours leads to 40%–85% inhibition of pAKT in all cell lines tested. GDC-0941 also inhibits the PI3K/AKT pathway by reducing cell proliferation/viability in a dose dependent manner. GDC-0941 inhibits the growth of both trastuzumab-sensitive and -insensitive cells.

Animal experiment [2]:

Animal models

U87MG human glioblastoma xenografts

Dosage form

Orally at 75 mg/kg daily

Applications

GDC-0941 inhibits the tumor growth by 83% after 21 days with no body weight loss. A dose-response relationship is also observed over the range 25-150 mg/kg/day. GDC-0941 also decreases the p-Akt levels as an indication of target inhibition.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Junttila TT, Akita RW, Parsons K et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009 May 5;15(5):429-40.

2. Folkes AJ, Ahmadi K, Alderton WK et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-t hieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer . J Med Chem. 2008 Sep 25;51(18):5522-32.

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Chemical Properties

Cas No. 957054-30-7 SDF Download SDF
Chemical Name 4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine
Canonical SMILES CS(=O)(=O)N1CCN(CC1)CC2=CC3=C(S2)C(=NC(=N3)C4=C5C=NNC5=CC=C4)N6CCOCC6
Formula C23H27N7O3S2 M.Wt 513.64
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips No
Shipping Condition No

Background

GDC-0941 is a novel selective class I phosphatidylinositol-3-kinase (PI3K) inhibitor. Activation of PI3K/Akt signaling pathway is frequently associated with tumorigenesis. Deregulation of this pathway occurs frequently with a variety of cancers and may contribute to the resistance to many anticancer agents. [1] Developing novel small molecules that specifically block the PI3K/Akt pathway may inhibit tumor growth. GDC-0941 is designed to bind the ATP-binding pocket of PI3K and to prevent formation of phosphatidylinositol-3, 4, 5-triphosphate (PIP3), a second messenger that transmits PI3K downstream signals. [2, 3] It binds to PI3K in an ATP-competitive manner.

GDC-0941 is a potent small-molecule thieno [3, 2-d] pyrimidine inhibitor of the class I PI3K. It is highly selective against isoforms p110( and p110( with IC50 of 3 nM, and moderately selective against isoforms p110( and p110( with IC50s of 33 nM and 75 nM, respectively.

GDC-0941 inhibits cell proliferation in vitro and in vivo. It causes growth inhibition in a variety of cancer cell lines, including A2780, MDA-MB-361, PC3, and U87MG. [2] It also inhibits the growth of trastuzumab–sensitive and –resistant HER2-amplied cancer cells which harbor p110( mutations or PTEN loss. [4] GDC-0941 also reduces tumor volume in different xenograft models. [4]

GDC-0941 can be taken orally.

References:
[1]Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008;27:5497-5510.
[2]Folkes AJ, Ahmadi K, Alderton WK, et al. The identification of 2-(1H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem. 2008; 51: 5522-5532.
[3]Knight ZA, Shokat KM. Chemically targeting the PI3K family. Biochem Soc Trans. 2007; 35: 245-249.
[4]Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Br J Cancer. 2011; 104(7): 1116-25.