VISTUSERTIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H30N6O3
Molecular Weight	462.5441
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=O)C1=CC=CC(=C1)C2=CC=C3C(N=C(N=C3N4CCOC[C@@H]4C)N5CCOC[C@@H]5C)=N2

InChI

InChIKey=JUSFANSTBFGBAF-IRXDYDNUSA-N

InChI=1S/C25H30N6O3/c1-16-14-33-11-9-30(16)23-20-7-8-21(18-5-4-6-19(13-18)24(32)26-3)27-22(20)28-25(29-23)31-10-12-34-15-17(31)2/h4-8,13,16-17H,9-12,14-15H2,1-3H3,(H,26,32)/t16-,17-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C25H30N6O3
Molecular Weight	462.5441
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/23375793|https://www.ncbi.nlm.nih.gov/pubmed/24311635

Vistusertib (AZ-2014) is a dual inhibitor of mTORC1/mTORC2 which was developed by AstraZeneca for the treatment of cancer. The drug is under clinical development (phase II) in patients with Renal Carcinoma, Squamous Non Small Cell Lung Cancer, Diffuse Large B-Cell Lymphoma, Meningioma, Breast cancer and Gastric cancer, either alone or in combination therapy. Vistusertib penetrates blood-brain barrier.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mammalian target of Rapamycin (mTORC1) 23 Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23375793	Inhibitor 8297		210.0 nM [IC50]
mTORC2 8 Target ID: mTORC2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23375793	Inhibitor 8297		78.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Renal cancer 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26364551	Primary	Phase II 1132	Unknown Approved Use Unknown
Meningioma 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26219339	Primary	Phase II 1132	Unknown Approved Use Unknown
Squamous non-small cell lung cancer 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02403895	Primary	Phase II 1132	Unknown Approved Use Unknown
Diffuse large B-cell lymphoma 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24970801	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26358751	Primary	Phase II 1132	Unknown Approved Use Unknown
Gastric adenocarcinoma 12 Sources: https://clinicaltrials.gov/ct2/show/NCT02449655	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699	CYP3A5 395 CYP2C8 693	P-gp 257

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677525	inconclusive [IC50 21.3174 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29790111/	likely
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29790111/	likely
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677525	no
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/29790111/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681558	yes [IC50 10.684 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681558	yes [IC50 15.0916 uM]

Drug as victim

Target	Modality	Activity
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25805799/	major
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25805799/	major
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25805799/	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/23375793/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116169	https://www.001chemical.com/chem/search?q=DY116169
1PlusChem LLC	1P0003OQ	https://www.1pchem.com/search?query=1P0003OQ
AChemBlock	10284	http://www.achemblock.com/catalogsearch/result/?q=10284
AK Scientific	SYN1167	https://aksci.com/item_detail.php?cat=SYN1167
AK Scientific	X3569	https://aksci.com/item_detail.php?cat=X3569
AOBIOUS INC	AOB3574	http://aobious.com/aobious/search?search_query=AOB3574
Ambeed	A386287	http://www.ambeed.com/search/Search.html?keyword=A386287
Angene	AGN-PC-0WA7WU	http://www.angenechemical.com/productshow/AGN-PC-0WA7WU.html
ApexBio Technology	A8373	https://www.apexbt.com/catalogsearch/result/?q=A8373
AstaTech	42554	http://astatechinc.com/CPSResult.php?CRNO=42554
BLD Pharm	BD291524	http://www.bldpharm.com/search/Search.html?keyword=BD291524
BOC Sciences	1009298-59-2	http://www.bocsci.com/description.asp?cas=1009298-59-2
Cayman Chemical	17378	http://www.caymanchem.com/app/template/Product.vm/catalog/17378
ChemShuttle	102702	https://www.chemshuttle.com/catalogsearch/result/?q=102702
Debye Scientific	DA-35312	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-35312
Excenen	EX-A155	http://www.excenen.com/searchresultlist.php?id=EX-A155
KeyOrganics	AS-16302	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16302
Lab Seeker	SC-62590	http://www.labseeker.com/search.php?keywords=SC-62590&category=0
LabSeeker	SC-62590	http://www.labseeker.com/search.php?keywords=SC-62590&category=0
Matrix Scientific	131592	http://www.matrixscientific.com/131592.html
MedChem Express	HY-15247	https://www.medchemexpress.com/search.html?q=HY-15247&ft=&fa=&fp=
MolPort	MolPort-023-293-553	https://www.molport.com/shop/molecule-link/MolPort-023-293-553
Molcore	MC116169	http://www.molcore.com/CatMC116169.html
Molnova	M10062	https://www.molnova.com/en/serch-list.html?keywords=M10062
MuseChem	I000107	https://www.musechem.com/product/I000107.html
ShangHai Biochempartner	BCP000631	http://www.biochempartner.com/search_BCP000631
ShangHai Biochempartner	BCP05748	http://www.biochempartner.com/search_BCP05748
TargetMol	T1961	https://www.targetmol.com/search?keyword=T1961
Toronto Research Chemicals	A808115	https://www.trc-canada.com/product-detail/?CatNum=A808115
Toronto Research Chemicals	H969900	https://www.trc-canada.com/product-detail/?CatNum=H969900
eMolecules	108760546	https://orderbb.emolecules.com/search/#?query=108760546
eMolecules	44786305	https://orderbb.emolecules.com/search/#?query=44786305
eNovation Chemicals	D210870	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D210870&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D572836	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D572836&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5509729271	https://mcule.com/MCULE-5509729271/
mcule	MCULE-9455167791	https://mcule.com/MCULE-9455167791/

PubMed

Title	Date	PubMed
Transforming growth factor-β (TGF-β) induces the expression of chondrogenesis-related genes through TGF-β receptor II (TGFRII)-AKT-mTOR signaling in primary cultured mouse precartilaginous stem cells.	2014 Jul 18	24946212
Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity.	2016 Sep 2	27343560

Patents

Sample Use Guides

In Vivo Use Guide

Renal Carcinoma: patients receive 50mg twice a day. Squamous Non Small Cell Lung Cancer: patients receive study treatment consisting of a single weekly paclitaxel infusion (80 mg/m2) on Day 1 of each week and twice daily 50 mg doses of vistusertib on the first 3 days each week for 6 weeks. Diffuse Large B-Cell Lymphoma: patients receive 125mg of vistusertib twice daily - 2 days on 5 days off in a 28 day cycle. Gastric Adenocarcinoma: patients receive 50mg of vistusertib twice dayly, 3 days on 4 days off of a 7 day cycle + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle.

Route of Administration: Oral

In Vitro Use Guide

Glioblastoma stem-like cells were treated with vistusertib (2 uM) and radiation to investigate the effects of the drug on the radiosensitivity of cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:31:18 GMT 2023` Edited by `admin` on `Sat Dec 16 10:31:18 GMT 2023`
Record UNII	0BSC3P4H5X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VISTUSERTIB

Official Name

English

AZD2014

Code

English

AZD-2014

Code

English

BENZAMIDE, 3-(2,4-BIS((3S)-3-METHYL-4-MORPHOLINYL)PYRIDO(2,3-D)PYRIMIDIN-7-YL)-N-METHYL-

Systematic Name

English

Vistusertib [WHO-DD]

Common Name

English

VISTUSERTIB [JAN]

Common Name

English

3-[2,4-Bis[(3S)-3-methyl-4-morpholinyl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide

Systematic Name

English

vistusertib [INN]

Common Name

English

VISTUSERTIB [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825