1. Product Overview
GSK2636771 (CAS: 1372540-25-4), systematically named 2-Methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid, is a potent, highly selective, and orally bioavailable small-molecule inhibitor targeting phosphoinositide 3-kinase beta (PI3Kβ). With a Kᵢ of 0.89 nM and IC₅₀ of 5.2 nM against PI3Kβ, it exhibits over 900-fold selectivity versus PI3Kα and PI3Kγ, and >10-fold over PI3Kδ. As a first-in-class PI3Kβ probe, it is specifically engineered to target PTEN-deficient tumors by blocking the PI3Kβ–p110β axis that compensates for PTEN loss in cancers such as prostate (PC-3), breast (HCC70), and glioblastoma. This compound is an essential pharmacological tool for dissecting isoform-specific PI3K signaling and evaluating synthetic-lethality strategies in oncology.
2. Key Features and Advantages
• Exceptional Isoform Selectivity: >900-fold selective for PI3Kβ (p110β) over PI3Kα/p110α and PI3Kγ/p110γ; >10-fold over PI3Kδ/p110δ, enabling clean mechanistic studies without confounding pan-PI3K effects.
• Picomolar Potency: Kᵢ = 0.89 nM, IC₅₀ = 5.2 nM for PI3Kβ; EC₅₀ of 36 nM in PTEN-null PC-3 cells and 72 nM in HCC70 cells, ensuring robust pathway suppression at low nanomolar working concentrations.
• Oral Bioavailability & In Vivo Suitability: Optimized physicochemical properties allow oral dosing in murine models (e.g., 100 mg/kg p.o.), with demonstrated reduction of phosphorylated Akt (Ser473) in PTEN-deficient xenografts without elevating systemic glucose/insulin levels.
• PTEN-Synthetic Lethality Probe: Specifically sensitizes PTEN-loss cell lines while sparing PTEN-intact cells, making it the gold-standard tool for PTEN-status stratification in drug discovery screens.
• Research-Grade Purity: Supplied at ≥98% (HPLC, typically 99.88% from MCE), with full CoA including ¹H NMR, LC-MS, and elemental analysis for batch-consistent in vitro/in vivo data.
• Stable Salt-Free Acid Form: The free carboxylic acid form offers predictable pKa behavior and straightforward DMSO/vehicle formulation for both cell culture and animal studies.
3. Main Applications
• Oncology & PI3K Pathway Research: Used in PTEN-deficient cancer models (prostate PC-3, breast HCC70, glioblastoma U87MG PTEN⁻/⁻) to evaluate PI3Kβ-dependence via Western blot (p-Akt Ser473, p-PRAS40), proliferation assays (CellTiter-Glo), and colony formation.
• Synthetic Lethality & Biomarker Studies: Employed to validate PTEN loss as a predictive biomarker; comparative treatment of isogenic PTEN⁺/⁻ pairs clarifies on-target vs off-target cytotoxicity.
• In Vivo Xenograft Models: Administered orally or via IP injection (typically 50–100 mg/kg/day in 0.5% HPMC/0.1% Tween-80 or 5% DMSO/95% corn oil) to assess tumor growth inhibition, pharmacokinetics, and PD marker modulation in nude mice.
• High-Content Screening & Counter-Screens: Serves as a reference selective PI3Kβ inhibitor in kinase panel profiling, counter-screening novel PI3Kα/δ/γ probes, and validating isoform-specific phenotypes in 3D spheroid/organoid cultures.
• Metabolic Safety Profiling: Applied in glucose-tolerance tests (GTT) and insulin measurements, since unlike PI3Kα inhibitors, GSK2636771 at efficacious doses does not significantly perturb systemic glucose homeostasis—a key differentiator for PI3Kβ-focused programs.
4. Technical Specifications
5. Storage and Handling
• Powder Storage: Store the original sealed vial at -20°C in a desiccator, protected from light and moisture. Stable for ≥2 years at -20°C; 6–12 months at 4°C if kept dry and sealed. For long-term archiving, inert atmosphere (argon/nitrogen) is recommended.
• Reconstitution: Allow vial to reach room temperature before opening to prevent moisture uptake. Briefly centrifuge, then dissolve in anhydrous DMSO to 10 mM stock (gentle vortexing or brief 37°C sonication may be needed; compound is slightly soluble in DMSO, ensure clear solution). Alternative: dissolve in minimal MeOH then dilute into DMSO/PBS for cell work.
• Solution Storage: Immediately aliquot DMSO stock into single-use volumes (10–50 µL). Store aliquots at -80°C (stable ≤6–12 months); short-term at -20°C (≤1 month). Strictly avoid repeated freeze-thaw cycles—thaw only required aliquot on ice.
• In Vivo Formulation: For oral gavage, suspend in 0.5% hydroxypropyl methylcellulose (HPMC) + 0.1% Tween-80, or formulate in 5% DMSO / 95% corn oil with mild warming to clarity. Typical dose range 50–100 mg/kg/day.
• Handling Precautions: Use in fume hood with nitrile gloves, safety goggles, lab coat. Minimize dust; keep container tightly closed when not in use.
6. Safety Overview
GSK2636771 is intended exclusively for Laboratory Research Use Only (LRUO). Not for human or veterinary diagnostic, therapeutic, or consumable use. GHS classification: GHS07 (Warning), H302 (Harmful if swallowed), H315 (Causes skin irritation), H319 (Causes eye irritation), H335 (May cause respiratory irritation). In case of skin contact, wash thoroughly with soap and water. Eye contact: rinse with flowing water ≥15 min, seek medical advice. If inhaled, move to fresh air. Dispose as hazardous organic chemical waste per local regulations. Always consult the full Safety Data Sheet (SDS) before handling.
— C ompany Profile ——
Jinan Topfull Chemical Co., Ltd. is an international company rooted in China, specializing in the export of chemical products.
Our company is committed to making every effort to provide ideal chemical products to potential customers worldwide, including but not limited to: organic/inorganic reagents, biological reagents, plant extracts, pharmaceutical intermediates, active pharmaceutical ingredients (APIs), reference standards, reference substances, peptides, and more. Meanwhile, we have established long-term and stable cooperative relationships with university laboratories and off-campus research institutions, enabling us to offer tailored product services based on customers' actual needs.
We currently support customized services for most product categories, with supply quantities ranging from milligram (mg), gram (g) to kilogram (kg) levels, as well as wholesale. Product purity covers the full spectrum from 90% to 99.9%, providing customers with one-stop convenient services.
To date, our products have been exported to developed countries such as the United States, Australia, Canada, Mexico, as well as EU member states including France, Germany, and many other countries and regions such as Nigeria, Ghana, Southeast Asia, and other parts of Asia. Our product quality and services have consistently received high praise.
Looking ahead, our company will continue to serve as a bridge connecting China and the world, delivering high-quality products and services to global customers.
—— Q&A ——
Q1: How to confirm the product quality before placing orders?
A: By sending you available samples. Or if you have special requirements for the goods, we can prepare samples according to your requirements for confirmation.
Q2: Can you supply free samples?
A: Yes, we can provide a free sample, but the shipping cost will be paid by the customers. You can either pay the shipping cost or arrange a courier to collect the samples.
Q3: How do you treat quality complaints?
A: All our products are strictly tested by our QC and confirmed by QA; unqualified material will not be released to customers. If any quality problem is confirmed to be caused by us, we will replace the goods or refund your payment immediately.
Q4: What is your MOQ? Is there a discount?
A: For high value products, our MOQ starts from 1g and generally starts from 10g. For other low price products, our MOQ starts from 100g and 1kg.
Q: Is there a discount?
A: Yes, for larger quantities, we always support with better prices.
Q5: How to start orders or make payments?
A: You can send us your Purchase Order (if your company has one), or just send a simple confirmation by email or via Trade Manager. We will then send you a Proforma Invoice with our bank details for your confirmation, and you can make payment accordingly. If you have other preferred payment methods, we are open to discussion and negotiation.
