AZD-8055

Investigational

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 Search

SMILES

COC1=C(CO)C=C(C=C1)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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20028854 | https://www.ncbi.nlm.nih.gov/pubmed/22143671
Curator's Comment: Description was created based on several sources, including http://en.pharmacodia.com/web/drug/1_1535.html https://www.ncbi.nlm.nih.gov/pubmed/25385646

AstraZeneca was developing AZD-8055, an orally active mTORC1/mTORC2 inhibitor, for the treatment of advanced solid tumours. AZD-8055 is an ATP-competitive mTORC1/2 inhibitor that exhibits immunosuppressive and anticancer chemotherapeutic activities. AZD-8055 promotes antibody class switching in B cells at low doses and decreases B cell proliferation and differentiation at high doses. In vivo, this compound suppresses CC4 and CD8 T cell proliferation, increasing survival among MHC-mismatched heart transplant recipients. In vitro, AZD-8055 decreases viability of brain tumor cells; in vivo, it inhibits tumor growth. AZD-8055 had been in phase I trials by AstraZeneca for the treatment of malignant gliomas and solid tumours. However, this research has been discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20028854	Inhibitor 8504		0.8 nM [IC50]
Mammalian target of Rapamycin (mTORC1) 23 Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23375793	Inhibitor 8504		27.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Solid tumors 147 Sources: https://clinicaltrials.gov/ct2/show/NCT00731263 http://adisinsight.springer.com/drugs/800028731	Primary	Phase I 438	Unknown Approved Use Unknown
Malignant glioma 10 Sources: https://clinicaltrials.gov/ct2/show/NCT01316809	Primary	Phase I 438	Unknown Approved Use Unknown
Oligodendroglioma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT01316809	Primary	Phase I 438	Unknown Approved Use Unknown
Anaplastic astrocytoma 6 Sources: https://clinicaltrials.gov/ct2/show/NCT01316809	Primary	Phase I 438	Unknown Approved Use Unknown
Glioblastoma multiforme 30 Sources: https://clinicaltrials.gov/ct2/show/NCT01316809	Primary	Phase I 438	Unknown Approved Use Unknown
Hepatocellular carcinoma 83 Sources: https://clinicaltrials.gov/ct2/show/NCT00999882	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
177 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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
70.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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

AUC

Value	Dose	Analyte	Population
294 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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
134 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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
122 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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

T_1/2

Value	Dose	Analyte	Population
3.14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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
2.36 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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
2.63 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22935583	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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	Human hepatocytes 3 P-gp 2052 BCRP 697

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29720580/	yes

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27553832/	yes
Human hepatocytes 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23375793/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27553832/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/23375793/

PubMed

Title	Date	PubMed
mTOR/p70S6K signaling distinguishes routine, maintenance-level autophagy from autophagic cell death during influenza A infection.	2014-03	24606695
PI3Kδ inhibition augments the efficacy of rapamycin in suppressing proliferation of Epstein-Barr virus (EBV)+ B cell lymphomas.	2013-08	23841834
Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014.	2013-03-01	23375793
TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO.	2012-05-02	22560223
Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice.	2011-03-29	21407213
Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer.	2011-03-10	21322566
Mammalian autophagy: core molecular machinery and signaling regulation.	2010-04	20034776
AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity.	2010-01-01	20028854
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.	2009-07-16	19587680
Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.	2004-07-27	15268862
Regulation of longevity and stress resistance by Sch9 in yeast.	2001-04-13	11292860

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Mon Mar 31 19:09:45 GMT 2025` Edited by `admin` on `Mon Mar 31 19:09:45 GMT 2025`
Record UNII	970JJ37FPW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AZD-8055

Code

English

AZ-12600000

Preferred Name

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