Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H31N9O3 |
| Molecular Weight | 469.54 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN1N=C(N=C1C2=NC(C3=NN=C(O3)C(C)(C)C)=C(N)N=C2)C4CCN(CC4)C(=O)CCO
InChI
InChIKey=ZGRDYKFVDCFJCZ-UHFFFAOYSA-N
InChI=1S/C22H31N9O3/c1-5-31-19(26-18(29-31)13-6-9-30(10-7-13)15(33)8-11-32)14-12-24-17(23)16(25-14)20-27-28-21(34-20)22(2,3)4/h12-13,32H,5-11H2,1-4H3,(H2,23,24)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/26839307 | https://openinnovation.astrazeneca.com/azd8835.htmlCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26475521
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26839307 | https://openinnovation.astrazeneca.com/azd8835.html
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26475521
AZD-8835 is a potent inhibitor of PI3Kα and PI3Kδ with selectivity versus PI3Kβ, PI3Kγ, and other kinases that preferentially inhibited growth in cells with mutant PIK3CA status, such as in estrogen receptor-positive (ER(+)) breast cancer cell lines BT474, MCF7, and T47D (sub-umol/L GI50s). Consistent with this, AZD-8835 demonstrated antitumor efficacy in corresponding breast
cancer xenograft models when dosed continuously. AZD-8835 is a selective, oral inhibitor of PI3K isoforms α and δ with the following activity in enzymatic assays: PI3K α – IC50 = 6nM (equipotent vs wt and E545K / H1047R mutants); PI3K δ – IC50 = 6nM; PI3K γ – IC50 = 90nM; PI3K β – IC50 = 431nM. Inhibition of signalling in cells (pAKT endpoint): PI3K α – IC50 = 57nM; PI3K δ – IC50 = 49nM; PI3K β – IC50 = 3.6uM; PI3K γ - IC50 = 532nM. AZD-8835 is in phase I clinical studies by AstraZeneca for the treatment of advanced solid tumors and ER+ and HER-2 negative breast cancer.
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
34 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26475521 |
50 mg/kg single, oral dose: 50 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
AZD-8835 plasma | Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
137 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26475521 |
50 mg/kg single, oral dose: 50 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
AZD-8835 plasma | Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
17% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26475521 |
50 mg/kg single, oral dose: 50 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
AZD-8835 plasma | Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
Sample Use Guides
Mice: Inhibition of signalling in MCF7 human xenograft in mice (pAKT endpoint): >90% 1 hour after administration of 25mg/kg. The compound demonstrated complete tumour growth inhibition at 25mg/kg continuous dosing, twice daily, orally, in MCF7 xenograft model (human xenograft tumour growth model in mice).
Route of Administration:
Oral
AZD-8835 inhibited p-Akt in T-ALL cells sensitive to PI3Kα inhibition (IC50=0.057 uM in PIK3CA mutant human breast ductal carcinoma BT474 cell line) and in cells sensitive to PI3Kδ inhibition (IC50=0.049 uM in JeKo-1 B cell line), but not to cells sensitive to PI3Kβ inhibition (IC50=3.5 uM in PTEN null breast adenocarcinoma MDA-MB-468 cell line) or PI3Kγ inhibition (IC50=0.53 uM in monocytic RAW264 cell line)
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1620576-64-8
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8B97A88D35
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76685059
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C118624
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ACTIVE MOIETY
