AZD-1208

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H21N3O2S
Molecular Weight	379.475
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@@H]1CCCN(C1)C2=C(C=CC=C2\C=C3/SC(=O)NC3=O)C4=CC=CC=C4

InChI

InChIKey=MCUJKPPARUPFJM-UWCCDQBKSA-N

InChI=1S/C21H21N3O2S/c22-16-9-5-11-24(13-16)19-15(12-18-20(25)23-21(26)27-18)8-4-10-17(19)14-6-2-1-3-7-14/h1-4,6-8,10,12,16H,5,9,11,13,22H2,(H,23,25,26)/b18-12-/t16-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C21H21N3O2S
Molecular Weight	379.475
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24363397 | https://www.ncbi.nlm.nih.gov/pubmed/27054578 | https://www.ncbi.nlm.nih.gov/pubmed/25505253 | https://openinnovation.astrazeneca.com/azd1208.html | http://en.pharmacodia.com/web/drug/1_654.html

AZD-1208 is an orally available, potent and highly selective Pim inhibitor that effectively inhibits all three isoforms. AZD-1208 inhibits the growth of several AML cell lines and sensitivity correlates with the level of Pim-1 expression, STAT5 activation and presence of protein tyrosine kinase mutation. AZD-1208 causes cell cycle arrest and apoptosis in MOLM-16 cells in culture. This is accompanied by a dose-dependent reduction in phosphorylation of BAD, 4EBP1 and p70S6K. In addition, AZD-1208 leads to potent inhibition of colony growth of primary AML cells from bone marrow aspirates and downregulates phosphorylation of Pim targets. AZD-1208 was in Phase 1 trials to evaluate the safety and tolerability profile and to determine the maximum tolerated dose (MTD). There were two trials where AZD-1208 had been administered orally in AML and solid tumour (of all types) patients. The studies had being discontinued due to safety reasons.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase PIM1 13 Target ID: CHEMBL2147 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24363397	Inhibitor 8297	0.1 nM [Ki]
Serine/threonine-protein kinase PIM2 3 Target ID: CHEMBL4523 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24363397	Inhibitor 8297	1.92 nM [Ki]
Serine/threonine-protein kinase PIM3 9 Target ID: CHEMBL5407 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24363397	Inhibitor 8297	0.4 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 178 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25505253	Primary	Preclinical	Unknown Approved Use Unknown
Acute myeloid leukemia 136 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24363397	Primary	Phase I 428	Unknown Approved Use Unknown
Malignant lymphoma 10 Sources: http://adisinsight.springer.com/drugs/800035518 https://clinicaltrials.gov/ct2/show/NCT01588548	Primary	Phase I 428	Unknown Approved Use Unknown
Advanced solid cancer 28 Sources: http://adisinsight.springer.com/drugs/800035518 https://clinicaltrials.gov/ct2/show/NCT01588548	Primary	Phase I 428	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116189	https://www.001chemical.com/chem/search?q=DY116189
1PlusChem LLC	1P008TUD	https://www.1pchem.com/search?query=1P008TUD
AChemBlock	M15894	http://www.achemblock.com/catalogsearch/result/?q=M15894
AK Scientific	2236AH	https://aksci.com/item_detail.php?cat=2236AH
AK Scientific	SYN1214	https://aksci.com/item_detail.php?cat=SYN1214
AOBIOUS INC	AOB87151	http://aobious.com/aobious/search?search_query=AOB87151
Ambeed	A178546	http://www.ambeed.com/search/Search.html?keyword=A178546
Angene	AGN-PC-0WAL58	http://www.angenechemical.com/productshow/AGN-PC-0WAL58.html
ApexBio Technology	A3962	https://www.apexbt.com/catalogsearch/result/?q=A3962
AstaTech	42046	http://astatechinc.com/CPSResult.php?CRNO=42046
Axon MedChem	2795	https://www.axonmedchem.com/product/2795
BLD Pharm	BD304657	http://www.bldpharm.com/search/Search.html?keyword=BD304657
Cayman Chemical	20235	http://www.caymanchem.com/app/template/Product.vm/catalog/20235
Chem Scene	CS-1668	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1668
ChemShuttle	108247	https://www.chemshuttle.com/catalogsearch/result/?q=108247
Combi-Blocks	QJ-0873	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-0873
Fluorochem	468372	http://www.fluorochem.co.uk/Products/Product?code=468372
KeyOrganics	AS-16341	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16341
Lab Network	LN01274606	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01274606
Matrix Scientific	132280	http://www.matrixscientific.com/132280.html
MedChem Express	HY-15604	https://www.medchemexpress.com/search.html?q=HY-15604&ft=&fa=&fp=
MolPort	MolPort-035-395-904	https://www.molport.com/shop/molecule-link/MolPort-035-395-904
MolPort	MolPort-039-062-178	https://www.molport.com/shop/molecule-link/MolPort-039-062-178
Molcore	MC116189	http://www.molcore.com/CatMC116189.html
Molnova	M17879	https://www.molnova.com/en/serch-list.html?keywords=M17879
MuseChem	I000752	https://www.musechem.com/product/I000752.html
MuseChem	I013056	https://www.musechem.com/product/I013056.html
Selleck Chemicals	S7104	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7104
TargetMol	T2300	https://www.targetmol.com/search?keyword=T2300
eMolecules	108762436	https://orderbb.emolecules.com/search/#?query=108762436
eMolecules	276004705	https://orderbb.emolecules.com/search/#?query=276004705
eMolecules	301116843	https://orderbb.emolecules.com/search/#?query=301116843
eMolecules	313089555	https://orderbb.emolecules.com/search/#?query=313089555
eMolecules	53925853	https://orderbb.emolecules.com/search/#?query=53925853
eNovation Chemicals	K31331	https://www.enovationchem.com/Products.asp?SEARCHTEXT=K31331&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-2599503158	https://mcule.com/MCULE-2599503158/
mcule	MCULE-6381792243	https://mcule.com/MCULE-6381792243/
mcule	MCULE-9286940917	https://mcule.com/MCULE-9286940917/

PubMed

Title	Date	PubMed
Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM Kinase Inhibitors.	2013 Dec 12	24900629

Patents

Sample Use Guides

In Vivo Use Guide

Mice: The in vivo activity of AZD-1208 was assessed in a MOLM-16 xenograft model treated daily for 2 weeks with drug or vehicle control. Dose-dependent inhibition of MOLM-16 tumor growth was observed. Treatment with 10 mg/kg or 30 mg/kg of AZD-1208 (the latter representing the typical maximum-tolerated dose on this treatment schedule) led to 89% tumor growth inhibition or slight regression, respectively. PD analyses following a single dose of 30 mg/kg showed strong suppression of pBAD, p4EBP1, and p-p70S6K for up to 12 hours after dosing.

Route of Administration: Oral

In Vitro Use Guide

In enzymatic assays carried out at a concentration of ATP that leads to half-maximal reaction velocity, AZD-1208 inhibited kinase activity with an IC50 of 0.4 nM for Pim-1, 5.0 nM for Pim-2, and 1.9 nM for Pim-3. In enzyme assays using 5 mM ATP, the high end of physiologic ATP concentration in human cells, the IC50 values were 2.6 nM for Pim-1, 164 nM for Pim-2, and 17 nM for Pim-3.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:49:00 GMT 2023` Edited by `admin` on `Sat Dec 16 01:49:00 GMT 2023`
Record UNII	S98NFM1378
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AZD-1208

Common Name

English

AZD 1208 [WHO-DD]

Common Name

English

Code System Code Type Description

SMS_ID

100000175798