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

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
Mammalian cyclin-dependent kinases.	2005 Nov	16236519
Cyclin-dependent kinase pathways as targets for cancer treatment.	2006 Apr 10	16603719
Cyclins and CDKS in development and cancer: lessons from genetically modified mice.	2006 Jan 1	16146805
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	19509270

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.

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