AZD-5438

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19370178 | https://www.ncbi.nlm.nih.gov/pubmed/19509270

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclin-dependent kinase 2/cyclin E 10 Target ID: CHEMBL2094126 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19370178	Inhibitor 8297	6.0 nM [IC50]
Cyclin-dependent kinase 2/cyclin A 8 Target ID: CHEMBL2094128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19370178	Inhibitor 8297	45.0 nM [IC50]
Cyclin-dependent kinase 1/cyclin B1 6 Target ID: CHEMBL1907602 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19370178	Inhibitor 8297	16.0 nM [IC50]
CDK6/cyclin D3 1 Target ID: CHEMBL2111448 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19370178	Inhibitor 8297	21.0 nM [IC50]
CDK9/cyclin T1 4 Target ID: CHEMBL2111389 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19509270	Inhibitor 8297	20.0 nM [IC50]
Cyclin-dependent kinase 5/CDK5 activator 1 8 Target ID: CHEMBL1907600 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19509270	Inhibitor 8297	14.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19825886	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
155 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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

Value	Dose	Analyte	Population
392 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19825886/	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

Dose	Population	Adverse events
60 mg single, oral (unknown) MTD Dose: 60 mg Route: oral Route: single Dose: 60 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	healthy n = 4 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	Other AEs: nausea, Dizziness... Other AEs: nausea (grade 1, 3 patients) Dizziness (grade 1, 1 pt) Dyspepsia (grade 1, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/17115157
160 mg single, oral (unknown) Studied dose Dose: 160 mg Route: oral Route: single Dose: 160 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	DLT: Nausea, vomiting... Dose limiting toxicities: Nausea (2 patients) vomiting (2 patients) Abdominal pain (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/17115157

AEs

AE	Significance	Dose	Population
Dizziness	grade 1, 1 pt	60 mg single, oral (unknown) MTD Dose: 60 mg Route: oral Route: single Dose: 60 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	healthy n = 4 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/17115157
Dyspepsia	grade 1, 1 pt	60 mg single, oral (unknown) MTD Dose: 60 mg Route: oral Route: single Dose: 60 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	healthy n = 4 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/17115157
nausea	grade 1, 3 patients	60 mg single, oral (unknown) MTD Dose: 60 mg Route: oral Route: single Dose: 60 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	healthy n = 4 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/17115157
Abdominal pain	2 patients DLT	160 mg single, oral (unknown) Studied dose Dose: 160 mg Route: oral Route: single Dose: 160 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17115157
Nausea	2 patients DLT	160 mg single, oral (unknown) Studied dose Dose: 160 mg Route: oral Route: single Dose: 160 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17115157
vomiting	2 patients DLT	160 mg single, oral (unknown) Studied dose Dose: 160 mg Route: oral Route: single Dose: 160 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17115157	healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17115157

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00ECTG	https://www.1pchem.com/search?query=1P00ECTG
AChemBlock	10279	http://www.achemblock.com/catalogsearch/result/?q=10279
AK Scientific	X7441	https://aksci.com/item_detail.php?cat=X7441
AOBIOUS INC	AOB2219	http://aobious.com/aobious/search?search_query=AOB2219
ApexBio Technology	A8326	https://www.apexbt.com/catalogsearch/result/?q=A8326
AstaTech	40668	http://astatechinc.com/CPSResult.php?CRNO=40668
Axon MedChem	1966	https://www.axonmedchem.com/product/1966
BLD Pharm	BD160825	http://www.bldpharm.com/search/Search.html?keyword=BD160825
BOC Sciences	602306-29-6	http://www.bocsci.com/description.asp?cas=602306-29-6
Capot Chemical	19336	https://www.capotchem.com/search.do?q=19336
Cayman Chemical	21598	http://www.caymanchem.com/app/template/Product.vm/catalog/21598
Chem Scene	CS-0023	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0023
ChemShuttle	111972	https://www.chemshuttle.com/catalogsearch/result/?q=111972
Excenen	EX-A069	http://www.excenen.com/searchresultlist.php?id=EX-A069
KeyOrganics	AS-56007	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56007
Lab Network	LN01343373	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343373
Lab Seeker	SC-86030	http://www.labseeker.com/search.php?keywords=SC-86030&category=0
LabSeeker	SC-86030	http://www.labseeker.com/search.php?keywords=SC-86030&category=0
Matrix Scientific	147290	http://www.matrixscientific.com/147290.html
MedChem Express	HY-10012	https://www.medchemexpress.com/search.html?q=HY-10012&ft=&fa=&fp=
MolPort	MolPort-008-266-713	https://www.molport.com/shop/molecule-link/MolPort-008-266-713
Molnova	M15245	https://www.molnova.com/en/serch-list.html?keywords=M15245
MuseChem	I004265	https://www.musechem.com/product/I004265.html
Selleck Chemicals	S2621	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2621
ShangHai Biochempartner	BCP000286	http://www.biochempartner.com/search_BCP000286
ShangHai Biochempartner	BCP02271	http://www.biochempartner.com/search_BCP02271
TargetMol	T2506	https://www.targetmol.com/search?keyword=T2506
Tocris	3968	https://www.tocris.com/search.php?Type=QuickSearch&Value=3968
eMolecules	32279259	https://orderbb.emolecules.com/search/#?query=32279259
eNovation Chemicals	D372287	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372287&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7052631683	https://mcule.com/MCULE-7052631683/

PubMed

Title	Date	PubMed
		252160611
Cyclin D-dependent kinases, INK4 inhibitors and cancer.	2002 Mar 14	11960696

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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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