ADAVOSERTIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H32N8O2
Molecular Weight	500.5954
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCN(CC1)C2=CC=C(NC3=NC=C4C(=O)N(CC=C)N(C4=N3)C5=NC(=CC=C5)C(C)(C)O)C=C2

InChI

InChIKey=BKWJAKQVGHWELA-UHFFFAOYSA-N

InChI=1S/C27H32N8O2/c1-5-13-34-25(36)21-18-28-26(29-19-9-11-20(12-10-19)33-16-14-32(4)15-17-33)31-24(21)35(34)23-8-6-7-22(30-23)27(2,3)37/h5-12,18,37H,1,13-17H2,2-4H3,(H,28,29,31)

HIDE SMILES / InChI

Molecular Formula	C27H32N8O2
Molecular Weight	500.5954
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24013427
Curator's Comment: description was created based on several sources, including: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=594147 | http://adisinsight.springer.com/drugs/800028808 | https://ncats.nih.gov/files/AZD1775.pdf

AZD1775 selectively targets and inhibits WEE1, a tyrosine kinase that phosphorylates cyclin-dependent kinase 1 (CDK1, CDC2) to inactivate the CDC2/cyclin B complex. Inhibition of WEE1 activity prevents the phosphorylation of CDC2 and impairs the G2 DNA damage checkpoint. This may lead to apoptosis upon treatment with DNA damaging chemotherapeutic agents. Current ongoing trials of AZD1775 include monotherapy and combination therapy with certain DNA damaging agents in solid tumors, ovarian tumors, gynaecological cancer, non-small cell lung cancer. AZD1775 is genotoxic, which is considered to be a result of its mechanism of action. Common serious adverse events (with chemotherapy) include: febrile neutropenia, neutropenia, thrombocytopenia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase WEE1 3 Target ID: CHEMBL5491 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19887545	Inhibitor 8504		5.2 nM [IC50]
Tyrosine-protein kinase YES 4 Target ID: CHEMBL2073 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19887545	Inhibitor 8504		14.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer 160 Sources: https://ncats.nih.gov/files/AZD1775.pdf http://adisinsight.springer.com/drugs/800028808	Primary	Phase II 1147	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: http://adisinsight.springer.com/drugs/800028808	Primary	Phase II 1147	Unknown Approved Use Unknown
Adenocarcinoma of the pancreas 2 Sources: https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2014-01214&r=1	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
983 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25964244	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-1775 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
740 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25964244	225 mg 2 times / day multiple, oral dose: 225 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MK-1775 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
5893 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25964244	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-1775 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3990 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25964244	225 mg 2 times / day multiple, oral dose: 225 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MK-1775 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25964244	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-1775 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25964244	225 mg 2 times / day multiple, oral dose: 225 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MK-1775 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
20% EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863148/			MK-1775 plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, oral MTD Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33863809	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/33863809	Other AEs: neutropenia, Leukopenia... Other AEs: neutropenia (grade 4, 5 patients) Leukopenia (grade 4, 1 pt) anemia (grade 3, 1 pt) hyponatremia (grade 3, 1 pt) thrombocytopenia (grade 3, 2 patients) nausea (grade 3, 2 patients) vomiting (grade 2, 2 patients) fatigue (grade 2, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/33863809
400 mg 1 times / day multiple, oral Studied dose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33863809	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/33863809	DLT: neutropenia, Pancytopenia... Dose limiting toxicities: neutropenia (grade 4, 1 pt) Pancytopenia (grade 4, 1 pt) Fatigue (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/33863809
225 mg 2 times / day multiple, oral MTD Dose: 225 mg, 2 times / day Route: oral Route: multiple Dose: 225 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25964244	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25964244	Other AEs: Leucopenia, Lymphopenia... Other AEs: Leucopenia (grade 3, 1 pt) Lymphopenia (grade 3, 1 pt) anemia (grade 3, 1 pt) Thrombocytopenia (grade 3, 1 pt) Neutropenia (grade 3, 2 patients) Nausea (grade 3, 1 pt) Diarrhea (grade 3, 1 pt) Hypophosphatemia (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/25964244
300 mg 2 times / day multiple, oral Studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25964244	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25964244	DLT: Supraventricular tachyarrhythmia, Myelosuppression... Dose limiting toxicities: Supraventricular tachyarrhythmia (1 pt) Myelosuppression (grade 4, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/25964244

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	OATP1A2 67 OATP2B1 122 OAT3 391 P-gp 2052 BCRP 697

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677250	inconclusive [IC50 18.9991 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677250	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677250	no
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=137276027	yes [IC50 3.7221 uM]

Drug as victim

Target	Modality	Activity
OAT3 391	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28928160/	no
OATP2B1 122	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28928160/	no
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29147815/	yes
OATP1A2 67	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28928160/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29147815/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116012	https://www.001chemical.com/chem/search?q=DY116012
1PlusChem LLC	1P003AL1	https://www.1pchem.com/search?query=1P003AL1
A2B Chem	AB52885	http://a2bchem.com/prod/AB52885
AChemBlock	M15123	http://www.achemblock.com/catalogsearch/result/?q=M15123
AK Scientific	SYN5698	https://aksci.com/item_detail.php?cat=SYN5698
AK Scientific	X7493	https://aksci.com/item_detail.php?cat=X7493
Ambeed	A399066	http://www.ambeed.com/search/Search.html?keyword=A399066
Angene	AGN-PC-0WH8XO	http://www.angenechemical.com/productshow/AGN-PC-0WH8XO.html
AOBIOUS INC	AOB87173	http://aobious.com/aobious/search?search_query=AOB87173
ApexBio Technology	A5755	https://www.apexbt.com/catalogsearch/result/?q=A5755
AstaTech	27926	http://astatechinc.com/CPSResult.php?CRNO=27926
Axon MedChem	1494	https://www.axonmedchem.com/product/1494
Cayman Chemical	21266	http://www.caymanchem.com/app/template/Product.vm/catalog/21266
Chem Scene	CS-0105	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0105
ChemShuttle	101254	https://www.chemshuttle.com/catalogsearch/result/?q=101254
Combi-Blocks	QJ-1903	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-1903
eMolecules	36000452	https://orderbb.emolecules.com/search/#?query=36000452
eNovation Chemicals	D572857	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D572857&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A331	http://www.excenen.com/searchresultlist.php?id=EX-A331
Hairui	HR106075	http://www.hairuichem.com/en/product/search.do?q=HR106075
KeyOrganics	AS-17001	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17001
Lab Seeker	SC-94519	http://www.labseeker.com/search.php?keywords=SC-94519&category=0
LabSeeker	SC-94519	http://www.labseeker.com/search.php?keywords=SC-94519&category=0
Matrix Scientific	120722	http://www.matrixscientific.com/120722.html
mcule	MCULE-8668868093	https://mcule.com/MCULE-8668868093/
MedChem Express	HY-10993	https://www.medchemexpress.com/search.html?q=HY-10993&ft=&fa=&fp=
Molcore	MC116012	http://www.molcore.com/CatMC116012.html
Molnova	M16820	https://www.molnova.com/en/serch-list.html?keywords=M16820
MolPort	MolPort-016-633-227	https://www.molport.com/shop/molecule-link/MolPort-016-633-227
MuseChem	I005658	https://www.musechem.com/product/I005658.html
PI Chemicals	PI-38309	http://www.pipharm.com/catalog_products/PI-38309.html
Ryan Scientific	Mirabegron	https://ryansci.com/products?q=Mirabegron&list_q=&search_type=exact
ShangHai Biochempartner	BCP000191	http://www.biochempartner.com/search_BCP000191
ShangHai Biochempartner	BCP01928	http://www.biochempartner.com/search_BCP01928
TargetMol	T2077	https://www.targetmol.com/search?keyword=T2077

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

The starting dose was 225 mg twice per day over 2.5 days for 1 week of a 21-day cycle. With subsequent dose escalations, at 225 mg or 300 mg twice per day for 2.5 days per week for 2 consecutive weeks of a 21-day cycle.

Route of Administration: Oral

In Vitro Use Guide

AZD1775 inhibits Wee1 activity and induces DNA damage as well as G2 checkpoint escape in cell-based assays with an EC50 of about 80 nM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:00:02 GMT 2025` Edited by `admin` on `Mon Mar 31 18:00:02 GMT 2025`
Record UNII	K2T6HJX3I3
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ADAVOSERTIB

Official Name

English

AZD-1775

Preferred Name

English

1,2-DIHYDRO-1-(6-(1-HYDROXY-1-METHYLETHYL)-2-PYRIDINYL)-6-((4-(4-METHYL-1-PIPERAZINYL)PHENYL)AMINO)-2-(2-PROPEN-1-YL)-3H-PYRAZOLO(3,4-D)PYRIMIDIN-3-ONE

Systematic Name

English

1-[6-(2-Hydroxypropan-2-yl)pyridin-2-yl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-(prop-2-en-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one

Systematic Name

English

ADAVOSERTIB [USAN]

Common Name

English

3H-PYRAZOLO(3,4-D)PYRIMIDIN-3-ONE, 1,2-DIHYDRO-1-(6-(1-HYDROXY-1-METHYLETHYL)-2-PYRIDINYL)-6-((4-(4-METHYL-1-PIPERAZINYL)PHENYL)AMINO)-2-(2-PROPEN-1-YL)-

Systematic Name

English

MK-1775

Code

English

MK1775

Code

English

adavosertib [INN]

Common Name

English

Adavosertib [WHO-DD]

Common Name

English

AZD1775

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1967