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Details

Stereochemistry ACHIRAL
Molecular Formula C18H21N5O2S
Molecular Weight 371.457
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AZD-5438

SMILES

CC(C)N1C(C)=NC=C1C2=NC(NC3=CC=C(C=C3)S(C)(=O)=O)=NC=C2

InChI

InChIKey=WJRRGYBTGDJBFX-UHFFFAOYSA-N
InChI=1S/C18H21N5O2S/c1-12(2)23-13(3)20-11-17(23)16-9-10-19-18(22-16)21-14-5-7-15(8-6-14)26(4,24)25/h5-12H,1-4H3,(H,19,21,22)

HIDE SMILES / InChI

Molecular Formula C18H21N5O2S
Molecular Weight 371.457
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

AZD-5438 is an anti-cancer medicine which was developed by AstraZeneca. The drug is under development for the treatment of solid tumors in phase I of clinical trials. AZD-5438 exerts its anti-proliferative action both in vitro and in vivo by inhibiting cyclin-dependent kinases 1, 2 and 6 which are involved in the cell cycle.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
6.0 nM [IC50]
45.0 nM [IC50]
16.0 nM [IC50]
21.0 nM [IC50]
20.0 nM [IC50]
14.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
155 ng/mL
20 mg 4 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
24.2 ng/mL
2.5 mg 4 times / day steady-state, oral
dose: 2.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
150 ng/mL
10 mg 4 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
85.5 ng/mL
40 mg 4 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
27.7 ng/mL
5 mg 4 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
392 ng × h/mL
20 mg 4 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
58.7 ng × h/mL
2.5 mg 4 times / day steady-state, oral
dose: 2.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
411.1 ng × h/mL
10 mg 4 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
245 ng × h/mL
40 mg 4 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
62.2 ng × h/mL
5 mg 4 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AZD-5438 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
60 mg single, oral (unknown)
MTD
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
healthy
n = 4
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 4
Sources:
Other AEs: nausea, Dizziness...
Other AEs:
nausea (grade 1, 3 patients)
Dizziness (grade 1, 1 pt)
Dyspepsia (grade 1, 1 pt)
Sources:
160 mg single, oral (unknown)
Studied dose
Dose: 160 mg
Route: oral
Route: single
Dose: 160 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 8
Sources:
DLT: Nausea, vomiting...
Dose limiting toxicities:
Nausea (2 patients)
vomiting (2 patients)
Abdominal pain (2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Dizziness grade 1, 1 pt
60 mg single, oral (unknown)
MTD
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
healthy
n = 4
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 4
Sources:
Dyspepsia grade 1, 1 pt
60 mg single, oral (unknown)
MTD
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
healthy
n = 4
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 4
Sources:
nausea grade 1, 3 patients
60 mg single, oral (unknown)
MTD
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
healthy
n = 4
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 4
Sources:
Abdominal pain 2 patients
DLT
160 mg single, oral (unknown)
Studied dose
Dose: 160 mg
Route: oral
Route: single
Dose: 160 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 8
Sources:
Nausea 2 patients
DLT
160 mg single, oral (unknown)
Studied dose
Dose: 160 mg
Route: oral
Route: single
Dose: 160 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 8
Sources:
vomiting 2 patients
DLT
160 mg single, oral (unknown)
Studied dose
Dose: 160 mg
Route: oral
Route: single
Dose: 160 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M
Food Status: UNKNOWN
Population Size: 8
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Mammalian cyclin-dependent kinases.
2005 Nov
Cyclin-dependent kinase pathways as targets for cancer treatment.
2006 Apr 10
AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts.
2009 Jul
Patents

Sample Use Guides

In study 1, patients received four doses of AZD-5438 orally on day 1 and subsequently every 7 days. The starting dose was 40 mg/day in four divided doses. In study 2, patients received a single dose of AZD-5438 on day 1 followed by four times daily dosing for 14 consecutive days, followed by a 7-day rest period. The starting dose was 20 mg/day (5 mg q.i.d.). In study 3, patients received a single dose of AZD-5438 on the first day of the first cycle, followed by q.i.d. dosing there after in 28-day cycles, starting at 10 mg/day (2.5 mg q.i.d).
Route of Administration: Oral
Different cell lines were exposed to a range of concentrations of AZD-5438 for 48h. Multiple myeloma cell lines were seeded into 96-well plates in RPMI 1640 supplemented with 10% FCS and glutamine and dosed with AZD-5438 for 72 h. IC50 values were 0.22 uM (MCF7, breast cancer cell line), 0.32 uM (HCT-116, colon cancer cell line), 0.4 uM (NCI-H322, lung cancer cell line), 0.2 uM (PC-3, prostate cancer cell line), 1 uM (IM-9, Multiple myeloma), etc.
Substance Class Chemical
Created
by admin
on Sat Dec 16 20:17:18 GMT 2023
Edited
by admin
on Sat Dec 16 20:17:18 GMT 2023
Record UNII
276Z913G29
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AZD-5438
Common Name English
2-PYRIMIDINAMINE, 4-(2-METHYL-1-(1-METHYLETHYL)-1H-IMIDAZOL-5-YL)-N-(4-(METHYLSULFONYL)PHENYL)-
Systematic Name English
AZD 5438
Common Name English
Code System Code Type Description
CAS
602306-29-6
Created by admin on Sat Dec 16 20:17:19 GMT 2023 , Edited by admin on Sat Dec 16 20:17:19 GMT 2023
PRIMARY
SMS_ID
100000175773
Created by admin on Sat Dec 16 20:17:19 GMT 2023 , Edited by admin on Sat Dec 16 20:17:19 GMT 2023
PRIMARY
EPA CompTox
DTXSID501025680
Created by admin on Sat Dec 16 20:17:19 GMT 2023 , Edited by admin on Sat Dec 16 20:17:19 GMT 2023
PRIMARY
PUBCHEM
16747683
Created by admin on Sat Dec 16 20:17:19 GMT 2023 , Edited by admin on Sat Dec 16 20:17:19 GMT 2023
PRIMARY
FDA UNII
276Z913G29
Created by admin on Sat Dec 16 20:17:19 GMT 2023 , Edited by admin on Sat Dec 16 20:17:19 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
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TARGET -> INHIBITOR
IC50
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ACTIVE MOIETY