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| 10mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Pictilisib mesylate (also called GDC-0941 mesylate, Pictrelisib, RG7321 and GNE0941 mesylate) is a potent and orally available inhibitor of PI3Kα/δ (class I phosphatidylinositol 3 kinase) with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). It has potential anticancer activity. Tumorigenesis is frequently linked to activation of the PI3K/Akt signaling pathway. Deregulation of this pathway is common in a variety of cancers and may play a role in the resistance to many anticancer drugs. It may be possible to stop the growth of tumors by creating brand-new small molecules that specifically block the PI3K/Akt pathway. 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. It binds to PI3K in an ATP-competitive way.
| Targets |
p110α (IC50 = 3 nM); p110β (IC50 = 33 nM); p110δ (IC50 = 3 nM); p110γ (IC50 = 75 nM); p110α-H1047R (IC50 = 3 nM); p110α-E545K (IC50 = 3 nM); DNA-PK (IC50 = 1.23 μM); mTOR (Ki = 0.58 μM); Autophagy
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| ln Vitro |
GDC-0941 is equipotent against PI3Kα and PI3Kδ as well as PI3Kα mutants E545-K and H1047-R, displaying modest levels of selectivity against PI3Kβ (10-fold) and PI3Kγ (25-fold), and greater levels of selectivity against members of PI3K class II, III, and IV, including C2β, Vps34, DNA-PK, and mTOR. With IC50 values of 46 nM, 37 nM, and 28 nM, respectively.[1] With an IC50 of 149-944 nM, GDC-0941 treatment effectively reduces the proliferation of HER2-amplified cells that are both trastuzumab-sensitive and -insensitive. With an IC50 of 500 nM or less, GDC-0941 effectively inhibits the proliferation of HER2-amplified cells that have PIK3CA mutations and the viability of HER2-amplified breast cancer cells that lack PTEN and are resistant to trastuzumab.[2] The growth of HCT116, DLD1, and HT29 cells is significantly inhibited by GDC-0941, with GI50 values of 1081 nM, 1070 nM, and 157 nM, respectively. [3] GDC-0941 suppresses the population of centroblasts, induces apoptosis, and inhibits the proliferation of tumor cells.[4]
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| ln Vivo |
GDC-0941 has a 78% oral bioavailability due to limited microsomal metabolism [5]. In established human U87MG glioblastoma xenografts in female NCr athymic mice, administration of GDC-0941 at 75 mg/kg/day results in a significant inhibitory effect, with tumor growth inhibition of 83%. [1] In mice with HER2-amplified, trastuzumab-resistant MDA-MB-361.1 xenografts, oral administration of GDC-0941 at 150 mg/kg/day significantly slows tumor progression and induces potent tumor apoptosis. [2] Two weeks of treatment with GDC-0941 (75 mg/kg/day) results in a 40% reduction in the tumor size of spontaneous B-cell follicular lymphomas in PTEN+/-LKB1+/hypo mice. This tumor volume reduction is accompanied by the elimination of Akt, S6K, and SGK (serum and glucocorticoid protein kinase) protein phosphorylation.[4]
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| Enzyme Assay |
Scintillation proximity assay; Recombinant human PI3Kα, PI3Kβ, and PI3Kδ are coexpressed in a Sf9 baculovirus system with the p85α regulatory subunit and are purified as GST-fusion proteins using affinity chromatography on glutathione-sepharose. Scintillation proximity assay. Recombinant human PI3Kγ is similarly expressed and purified as monomeric GST-fusions. GDC-0941 is dissolved in DMSO and infused into a 50 μL mixture of 20 mM Tris-HCl (pH 7.5), 4 mM MgCl2, 1 mM DTT, 1 μM ATP, 0.125 μCi [γ-33P]-ATP, and 4% (v/v) DMSO. To start the kinase reaction, the assay mixture is mixed with the recombinant GST-fusion of PI3Kα (5 ng), PI3Kβ (5 ng), PI3Kδ (5 ng), or PI3Kγ (5 ng).
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| Cell Assay |
BT474-M1, SKBR-3, AU-565, HCC-1419, ZR75-30, JIMT-1, BT474-EEI, HCC-1954, MCF-7, CALU-3, SKOV-3, and MKN-7 cells are exposed to different concentrations of GDC-0941 for 48 and 72 hours. The CellTiter-Glo Luminescent Cell Viability Assay is used to identify cell viability and proliferation. By using a western blot, the pAkt (Ser473), cleaved caspase-3, and cleaved PARP are all examined. Apoptosis and caspase 3/7 activity are both detected using the Cell Death Detection ELISAplus assay and the Caspase-Glo 3/7 assay, respectively.
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| Animal Protocol |
Under the skin, MCF7-neo/HER2 or MX-1 breast cancer cells are injected into female nu/nu mice. Animals are distributed into groups of 10 animals each when tumors reach a mean volume of 200 to 250 mm3. Group sizes are determined by size matching. Once a week, intravenous RP-56976, a formulation of 3% EtOH and 97% saline, is given. Pictilisib (GDC-0941), a daily oral dose of MCT (0.5% methylcellulose, 0.2% Tween-80), is administered. By directly implanting tumors from patients under the skin of NMRI nu/nu mice, the MAXF1162 HER2+/ER+/PR+ patient-derived breast cancer tumor xenograft model was created. Volume of the tumor is calculated. Throughout a study, tumor size measurements are taken twice a week.
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| References |
| Molecular Formula |
C25H35N7O9S4
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| Molecular Weight |
705.84
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| Elemental Analysis |
C, 42.54; H, 5.00; N, 13.89; O, 20.40; S, 18.17
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| CAS # |
957054-33-0
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| Related CAS # |
Pictilisib;957054-30-7
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| Appearance |
Solid powder
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| SMILES |
CS(=O)(=O)N1CCN(CC1)CC2=CC3=C(S2)C(=NC(=N3)C4=C5C=NNC5=CC=C4)N6CCOCC6.CS(=O)(=O)O.CS(=O)(=O)O
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| InChi Key |
RFRIKACSFOTIMU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H27N7O3S2.2CH4O3S/c1-35(31,32)30-7-5-28(6-8-30)15-16-13-20-21(34-16)23(29-9-11-33-12-10-29)26-22(25-20)17-3-2-4-19-18(17)14-24-27-19;2*1-5(2,3)4/h2-4,13-14H,5-12,15H2,1H3,(H,24,27);2*1H3,(H,2,3,4)
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| Chemical Name |
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine;methanesulfonic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4168 mL | 7.0838 mL | 14.1675 mL | |
| 5 mM | 0.2834 mL | 1.4168 mL | 2.8335 mL | |
| 10 mM | 0.1417 mL | 0.7084 mL | 1.4168 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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