GSK-2636771 98% purity Pharmaceutical intermediate CAS 1372540-25-4 high purity, research chemical

Product Overview

GSK-2636771 is a potent, selective small‑molecule inhibitor of phosphoinositide 3‑kinase β (PI3Kβ). It binds reversibly to the ATP‑binding pocket of PI3Kβ, preventing phosphorylation of PIP2 to PIP3 and thereby shutting down the downstream Akt/mTOR signaling cascade that drives cell survival, proliferation, and migration in many cancers. The compound is particularly effective in tumor models harboring PTEN loss or PIK3CB (p110β) activating mutations, where it reduces tumor growth and sensitizes cells to chemotherapy or radiation. GSK‑2636771 is supplied as a grey‑colored powder with a guaranteed purity of ≥98% by HPLC, suitable for in‑vitro enzymatic assays, cellular signaling studies, and in‑vivo xenograft experiments. It displays excellent solubility in DMSO and can be formulated in aqueous buffers for cellular work. Preclinical pharmacology shows a favorable tolerability profile in rodents up to 100 mg/kg, and its pharmacokinetic properties support once‑daily oral dosing. The reagent is manufactured under GMP‑like conditions to meet Pharmaceutical Grade specifications, ensuring consistent quality and minimal batch‑to‑batch variation. It is recommended to store the solid at ‑20 °C, protected from light and moisture, to maintain stability for at least two years. In addition, GSK‑2636771 is used to probe PI3Kβ‑dependent signaling in immune cells, metabolic disorders, and neurological disease models, providing researchers with a versatile pharmacological tool. The compound’s selectivity profile has been confirmed across a panel of 400 kinases, showing >100‑fold selectivity over other PI3K isoforms and most off‑targets, which supports its utility in target‑validation studies.

Synthesis Process

The synthesis of GSK‑2636771 is accomplished in four main steps. First, 6‑bromo‑1H‑indazole is coupled with a boronate‑substituted indazole derivative via a Suzuki–Miyaura cross‑coupling to give a bi‑indazole intermediate. This intermediate is then subjected to a nucleophilic substitution with 2‑chloro‑1‑(propan‑2‑yl)‑1H‑imidazole to install the required thiazole moiety. After deprotection of the boc‑protecting group, the final product is purified by silica‑gel column chromatography and converted to its hydrochloride salt. The overall yield ranges from 30 % to 40 % and the final material meets ≥98 % purity by HPLC.

Quality Specifications

GSK‑2636771 is released against a comprehensive specification set to ensure consistency and safety. Purity is determined by HPLC and must be ≥98.0 %. Water content, measured by Karl Fischer titration, is ≤0.5 %. Residual solvents, including methanol, acetonitrile, and dimethylformamide, are each ≤0.1 % (ICH Q3C). Heavy metals are limited to ≤10 ppm. The product is tested for identity by 1H NMR and mass spectrometry, matching the expected molecular ion. Melting point is in the range of 195–200 °C. The compound is also checked for microbial limits, total plate count ≤100 CFU/g, and absence of mycoplasma. All results are documented in a Certificate of Analysis (CoA) supplied with each batch.

Packaging & Storage

GSK‑2636771 is packaged in amber glass vials to protect from light, with each vial sealed under nitrogen atmosphere. Standard package sizes are 1 g, 5 g, 10 g, and 25 g, and custom fill weights can be arranged upon request. The product should be stored at –20 °C in a dry place, away from direct sunlight and moisture. For short‑term use, the reagent may be kept at 2–8 °C for up to one month without significant degradation. After opening, the vial should be flushed with dry nitrogen and tightly capped to minimize exposure to humid air. The shelf life under recommended storage is at least 24 months.