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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H31N5O4
Molecular Weight 465.5447
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AZD-8055

SMILES

COC1=CC=C(C=C1CO)C2=NC3=NC(=NC(N4CCOC[C@@H]4C)=C3C=C2)N5CCOC[C@@H]5C

InChI

InChIKey=KVLFRAWTRWDEDF-IRXDYDNUSA-N
InChI=1S/C25H31N5O4/c1-16-14-33-10-8-29(16)24-20-5-6-21(18-4-7-22(32-3)19(12-18)13-31)26-23(20)27-25(28-24)30-9-11-34-15-17(30)2/h4-7,12,16-17,31H,8-11,13-15H2,1-3H3/t16-,17-/m0/s1

HIDE SMILES / InChI

Molecular Formula C25H31N5O4
Molecular Weight 465.5447
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23375793 | https://www.ncbi.nlm.nih.gov/pubmed/20561789 | https://www.ncbi.nlm.nih.gov/pubmed/20364113 | https://clinicaltrials.gov/ct2/show/NCT01316809

AZD8055 is a new ATP-competitive mTOR kinase inhibitor that was developed to overcome the limitations of the first generation of allosteric mTORC1 inhibitors (rapamycin and its analogs) as anticancer agents. AZD8055 potently and selectively inhibits mTOR by directly targeting its catalytic site, which results in the blockade of the activity of both mTORC1 and mTORC2 complexes. It displays antitumoral activity by inhibiting proliferation and/or inducing cell death in various cancer cell models, including ovarian clear cell carcinoma.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.8 nM [IC50]
27.0 nM [IC50]
0.13 nM [IC50]
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
70 ng/mL
90 mg single, oral
dose: 90 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
355 ng/mL
120 mg 2 times / day steady-state, oral
dose: 120 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
70.1 ng/mL
90 mg single, oral
dose: 90 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
177 ng/mL
120 mg single, oral
dose: 120 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
122 ng × h/mL
90 mg single, oral
dose: 90 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
501 ng × h/mL
120 mg 2 times / day steady-state, oral
dose: 120 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
134 ng × h/mL
90 mg single, oral
dose: 90 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
294 ng × h/mL
120 mg single, oral
dose: 120 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.63 h
90 mg single, oral
dose: 90 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.45 h
120 mg 2 times / day steady-state, oral
dose: 120 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.36 h
90 mg single, oral
dose: 90 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.14 h
120 mg single, oral
dose: 120 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-8055 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Regulation of longevity and stress resistance by Sch9 in yeast.
2001 Apr 13
Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.
2004 Jul 27
Mammalian autophagy: core molecular machinery and signaling regulation.
2010 Apr
Patents

Sample Use Guides

Mice: administration of AZD-8055 (5mg/kg, Bid) and SAHA (100 mg/kg/d) results in complete tumor growth inhibition in PTEN+/−LKB1+/hypo xenografts without side effects on mice by inhibition of mTORC1 and mTORC2 signaling
Route of Administration: Oral
AZD-8055 potently inhibits proliferation in U87MG, A549 and H838 cells with IC50 of 53, 50 and 20 nM, respectively.
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:17:49 GMT 2023
Edited
by admin
on Fri Dec 15 18:17:49 GMT 2023
Record UNII
970JJ37FPW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AZD-8055
Code English
AZ-12600000
Code English
(5-(2,4-BIS((3S)-3-METHYLMORPHOLIN-4-YL)PYRIDO(2,3-D)PYRIMIDIN-7-YL)-2-METHOXYPHENYL)METHANOL
Systematic Name English
AZD 8055 [WHO-DD]
Common Name English
AZD8055
Code English
Code System Code Type Description
PUBCHEM
25262965
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
FDA UNII
970JJ37FPW
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
CAS
1009298-09-2
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
ChEMBL
CHEMBL1801204
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
EPA CompTox
DTXSID001020704
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
NCI_THESAURUS
C78856
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
CHEBI
91329
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
DRUG BANK
DB12774
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
SMS_ID
100000175222
Created by admin on Fri Dec 15 18:17:49 GMT 2023 , Edited by admin on Fri Dec 15 18:17:49 GMT 2023
PRIMARY
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