GDC-0068 [1001264-89-6]

Catalog number: HY-15186_10mM
Brand: MedChem Express
Packing: 10 mM
Other sizes: 5 mg
10 mg
50 mg
100 mg
Price: € 101.00
Expected delivery time: 10 days

Product specifications for - GDC-0068 [1001264-89-6]

Product group: Chemicals
Category: Inhibitors / activators
CAS No.: 1001264-89-6
Purity: >98%
Molecular Formula: C24H32ClN5O2
Molecular weight: 457,9962
Datasheet: Datasheet
  Research Use Only
UNSPSC: 12352200
Scientific information: 
Scientific info: GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5/18/8 nM, 620-fold selectivity over PKA. IC50 & Target: IC50: 5+/-7 nM (Akt1), 18+/-10 nM (Akt2), 8+/-9 nM (Akt3), 3100+/-705 nM (PKA)[1] In Vitro: GDC-0068 shows more than 600 and more than 100-fold selectivity for Akt1 in IC50 against the closely related kinases PKA and p70S6K, respectively. When tested at 1 uM in a panel of 230 protein kinases, which includes 36 human AGC family members, GDC-0068 inhibits only 3 other kinases by more than 70% at 1 uM concentration (PRKG1alpha, PRKG1beta, and p70S6K). IC50s measured for these 3 kinases are 98, 69, and 860 nM, respectively. Thus, with the exception of PKG1 (relative to which GDC-0068 is >10-fold more selective for Akt1), GDC-0068 displays a more than 100-fold selectivity for Akt1 over the next most potently inhibited non-Akt kinase, p70S6K, in the screening kinase panel. The relationship between pharmacokinetics (PK) and pharmacodynamics (PD) of GDC-0068 is investigated in 3 xenograft models that showed dose-dependent response to drug treatment: MCF7-neo/HER2, TOV-21G.x1, and LNCaP. The mean cell viability IC50 of GDC-0068 in these 3 cell lines is 2.56, 0.44, and 0.11 uM, respectively[2]. In Vivo: GDC-0068 is typically efficacious in xenograft models in which Akt is activated because of genetic alterations including PTEN loss, PIK3CA mutations/amplifications, or HER2 overexpression. In these models, tumor growth delay, stasis, or regression is achieved at or below 100 mg/kg daily oral dose, which is the maximum dose tested in immunocompromised mice that is well tolerated. When tested in vivo, daily dosing of GDC-0068 in combination with Docetaxel induces tumor regression and stasis in the PC-3 and MCF7-neo/HER2 xenograft models, at doses where each single agent is ineffective or only causes modest tumor growth delay. Similarly, increased TGI is observed in the OVCAR3 ovarian cancer xenograft model when GDC-0068 is combined with Carboplatin. The combination of GDC-0068 with Docetaxel or Carboplatin is tolerated with less than 5% body weight loss when compared with treatment with each chemotherapeutic agent alone[2].
Safety information: 
Additional information: 
Synonyms: HY-15186