GDC-0077 98% Purity Active Pharmaceutical Ingredient CAS 2060571-02-8 breast cancer, API, oncology

Product Overview

GDC-0077 (also known as RG-6171) is a potent, selective, and orally bioavailable selective estrogen receptor α (ERα) degrader developed for the treatment of ER‑positive breast cancer. It binds to the ligand‑binding domain of ERα, induces a conformational change that promotes the recruitment of the E3 ubiquitin ligase complex, leading to polyubiquitination and proteasomal degradation of the receptor. In preclinical models, GDC‑0077 demonstrated strong antiproliferative activity in ER‑positive tumor cell lines and induced complete regression of xenograft tumors at well‑tolerated doses. The compound exhibits favorable pharmacokinetic properties, including high oral bioavailability, moderate clearance, and a half‑life supporting once‑daily dosing in clinical studies. GDC‑0077 is currently under evaluation in Phase I/II clinical trials as a single agent and in combination with CDK4/6 inhibitors for patients with advanced breast cancer. As an advanced‑stage small‑molecule SERD, GDC‑0077 represents a promising therapeutic option for endocrine‑resistant ER‑positive disease.

Synthesis Process

Efficient synthesis of GDC‑0077 begins with a Suzuki–Miyaura coupling of 1,2‑dimethylindole‑3‑boronic acid with 4‑bromoaniline to give the key 3‑(4‑aminophenyl)‑1,2‑dimethylindole intermediate. The amine is then acylated with 3‑(1‑methyl‑1H‑indol‑3‑yl)propionic acid under standard amide‑coupling conditions (EDC, HOBt, DIPEA) to afford the penultimate amide. Finally, a palladium‑catalyzed C‑N coupling installs the dimethylamino group, and the product is purified by silica‑gel chromatography to deliver GDC‑0077 with >98 % HPLC purity.

Quality Specifications

The product conforms to the following specifications: purity ≥98.0 % (HPLC), loss on drying ≤0.5 %, water content ≤0.5 %, heavy metals ≤10 ppm, residual solvents comply with ICH Q3C (ethanol ≤0.5 %, methanol ≤0.3 %, dimethyl sulfoxide ≤0.5 %). Melting point approximately 210 °C (decomposes). The assay is performed on a Waters Acquity UPLC system using a gradient of acetonitrile/0.1 % formic acid in water. Each batch is released only after passing all quality control tests and accompanied by a Certificate of Analysis.

Packaging & Storage

GDC‑0077 is supplied in amber glass vials (1 g, 5 g, 10 g, 25 g) sealed under an inert nitrogen atmosphere with a polytetrafluoroethylene (PTFE) lined screw cap. The product should be stored at ‑20 °C to ‑80 °C, protected from moisture and direct light. To maintain integrity, keep the container tightly closed and avoid repeated freeze–thaw cycles. Under these conditions the shelf life is 24 months from the date of manufacture.