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Details

Stereochemistry ACHIRAL
Molecular Formula 2C27H32N8O2.H2O
Molecular Weight 1019.206
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ADAVOSERTIB HEMIHYDRATE

SMILES

O.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.CN6CCN(CC6)C7=CC=C(NC8=NC=C9C(=O)N(CC=C)N(C9=N8)C%10=NC(=CC=C%10)C(C)(C)O)C=C7

InChI

InChIKey=BMQMRZXQRFUQIR-UHFFFAOYSA-N
InChI=1S/2C27H32N8O2.H2O/c2*1-5-13-34-25(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;/h2*5-12,18,37H,1,13-17H2,2-4H3,(H,28,29,31);1H2

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

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.2 nM [IC50]
14.0 nM [IC50]
Conditions
Doses

Doses

DosePopulationAdverse events​
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
Other AEs: vomiting, fatigue...
Other AEs:
vomiting (grade 2, 2 patients)
fatigue (grade 2, 1 pt)
anemia (grade 3, 1 pt)
hyponatremia (grade 3, 1 pt)
thrombocytopenia (grade 3, 2 patients)
nausea (grade 3, 2 patients)
Leukopenia (grade 4, 1 pt)
neutropenia (grade 4, 5 patients)
Sources:
400 mg 1 times / day multiple, oral (starting)
Studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: solid tumour
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
DLT: neutropenia, Pancytopenia...
Dose limiting toxicities:
neutropenia (grade 4, 1 pt)
Pancytopenia (grade 4, 1 pt)
Fatigue (grade 3, 1 pt)
Sources:
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
Other AEs: Neutropenia, Lymphopenia...
Other AEs:
Neutropenia (grade 3, 2 patients)
Lymphopenia (grade 3, 1 pt)
Thrombocytopenia (grade 3, 1 pt)
anemia (grade 3, 1 pt)
Leucopenia (grade 3, 1 pt)
Nausea (grade 3, 1 pt)
Diarrhea (grade 3, 1 pt)
Hypophosphatemia (grade 3, 1 pt)
Sources:
300 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy
n = 3
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
DLT: Myelosuppression, Supraventricular tachyarrhythmia...
Dose limiting toxicities:
Myelosuppression (grade 4, 1 pt)
Supraventricular tachyarrhythmia (1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
fatigue grade 2, 1 pt
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
vomiting grade 2, 2 patients
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
anemia grade 3, 1 pt
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
hyponatremia grade 3, 1 pt
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
nausea grade 3, 2 patients
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
thrombocytopenia grade 3, 2 patients
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
Leukopenia grade 4, 1 pt
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
neutropenia grade 4, 5 patients
300 mg 1 times / day multiple, oral (starting)
MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
Fatigue grade 3, 1 pt
DLT
400 mg 1 times / day multiple, oral (starting)
Studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: solid tumour
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
Pancytopenia grade 4, 1 pt
DLT
400 mg 1 times / day multiple, oral (starting)
Studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: solid tumour
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
neutropenia grade 4, 1 pt
DLT
400 mg 1 times / day multiple, oral (starting)
Studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: solid tumour
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
Diarrhea grade 3, 1 pt
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
Hypophosphatemia grade 3, 1 pt
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
Leucopenia grade 3, 1 pt
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
Lymphopenia grade 3, 1 pt
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
Nausea grade 3, 1 pt
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
Thrombocytopenia grade 3, 1 pt
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
anemia grade 3, 1 pt
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
Neutropenia grade 3, 2 patients
225 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 225 mg, 2 times / day
Route: oral
Route: multiple
Dose: 225 mg, 2 times / day
Sources:
unhealthy
n = 19
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 19
Sources:
Supraventricular tachyarrhythmia 1 pt
DLT, Disc. AE
300 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy
n = 3
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
Myelosuppression grade 4, 1 pt
DLT, Disc. AE
300 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy
n = 3
Health Status: unhealthy
Condition: solid tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

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 Fri Dec 15 17:39:57 GMT 2023
Edited
by admin
on Fri Dec 15 17:39:57 GMT 2023
Record UNII
NDV91627P9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ADAVOSERTIB HEMIHYDRATE
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)-, HYDRATE (2:1)
Systematic Name English
MK-1775 HEMIHYDRATE
Code English
Code System Code Type Description
CAS
1277170-60-1
Created by admin on Fri Dec 15 17:39:57 GMT 2023 , Edited by admin on Fri Dec 15 17:39:57 GMT 2023
PRIMARY
PUBCHEM
50992433
Created by admin on Fri Dec 15 17:39:57 GMT 2023 , Edited by admin on Fri Dec 15 17:39:57 GMT 2023
PRIMARY
FDA UNII
NDV91627P9
Created by admin on Fri Dec 15 17:39:57 GMT 2023 , Edited by admin on Fri Dec 15 17:39:57 GMT 2023
PRIMARY
SMS_ID
300000014641
Created by admin on Fri Dec 15 17:39:57 GMT 2023 , Edited by admin on Fri Dec 15 17:39:57 GMT 2023
PRIMARY
Related Record Type Details
ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY