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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H27N5O5
Molecular Weight 477.5124
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVN-944

SMILES

CC[C@H](CC#N)OC(=O)N[C@@H](C)C1=CC=CC(NC(=O)NC2=CC(OC)=C(C=C2)C3=CN=CO3)=C1

InChI

InChIKey=GYCPCOJTCINIFZ-OXJNMPFZSA-N
InChI=1S/C25H27N5O5/c1-4-20(10-11-26)35-25(32)28-16(2)17-6-5-7-18(12-17)29-24(31)30-19-8-9-21(22(13-19)33-3)23-14-27-15-34-23/h5-9,12-16,20H,4,10H2,1-3H3,(H,28,32)(H2,29,30,31)/t16-,20+/m0/s1

HIDE SMILES / InChI
Molecular Formula C25H27N5O5
Molecular Weight 477.5124
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

AVN-944 is an IMPDH (inosine 5-monophosphate dehydrogenase) inhibitor which is now being tested in phase I of clinical trials for the treatment of hematologic malignancies and solid tumors and in phase II for pancreatic cancer (in combination with gemcitabine). The drug showed good inhibition of IMPDH isoforms I and II with Ki=6-10 nM.

Originator

Vertex
26
Curator's Comment: Licensed by Avalon Pharmaceuticals.

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5418 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18971325
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVN-944 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
14540 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18971325
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVN-944 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.56 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18971325
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVN-944 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
250 mg single, oral
Highest studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/18971325
Page: p.35
healthy
n = 4
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/18971325
Page: p.35
Sources:
https://pubmed.ncbi.nlm.nih.gov/18971325
Page: p.35
Sourcing

Sourcing

Vendor/AggregatorIDURL
1PlusChem LLC
1P00BFM8
https://www.1pchem.com/search?query=1P00BFM8
AK Scientific
SYN5575
https://aksci.com/item_detail.php?cat=SYN5575
AOBIOUS INC
AOB5557
http://aobious.com/aobious/search?search_query=AOB5557
AstaTech
F13061
http://astatechinc.com/CPSResult.php?CRNO=F13061
BLD Pharm
BD450430
http://www.bldpharm.com/search/Search.html?keyword=BD450430
Cayman Chemical
21284
http://www.caymanchem.com/app/template/Product.vm/catalog/21284
Chem Scene
CS-3427
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3427
ChemShuttle
157279
https://www.chemshuttle.com/catalogsearch/result/?q=157279
Combi-Blocks
QV-3655
http://www.combi-blocks.com/cgi-bin/find.cgi?QV-3655
KeyOrganics
AS-16899
http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16899
Lab Seeker
SC-82478
http://www.labseeker.com/search.php?keywords=SC-82478&category=0
LabSeeker
SC-82478
http://www.labseeker.com/search.php?keywords=SC-82478&category=0
MedChem Express
HY-13560
https://www.medchemexpress.com/search.html?q=HY-13560&ft=&fa=&fp=
MolPort
MolPort-044-181-293
https://www.molport.com/shop/molecule-link/MolPort-044-181-293
Molnova
M13910
https://www.molnova.com/en/serch-list.html?keywords=M13910
MuseChem
I003029
https://www.musechem.com/product/I003029.html
Ryan Scientific
MK3697
https://ryansci.com/products?q=MK3697&list_q=&search_type=exact
TargetMol
T1979
https://www.targetmol.com/search?keyword=T1979
Toronto Research Chemicals
A794720
https://www.trc-canada.com/product-detail/?CatNum=A794720
eMolecules
301195741
https://orderbb.emolecules.com/search/#?query=301195741
eMolecules
50282741
https://orderbb.emolecules.com/search/#?query=50282741
eMolecules
89937146
https://orderbb.emolecules.com/search/#?query=89937146
mcule
MCULE-4503400571
https://mcule.com/MCULE-4503400571/
mcule
MCULE-9404960723
https://mcule.com/MCULE-9404960723/
PubMed

PubMed

TitleDatePubMed
Recent development of IMP dehydrogenase inhibitors for the treatment of cancer.
2007 Jul
Guanine nucleotide depletion inhibits pre-ribosomal RNA synthesis and causes nucleolar disruption.
2008 Jan
Antiproliferative effects of AVN944, a novel inosine 5-monophosphate dehydrogenase inhibitor, in prostate cancer cells.
2008 Nov 15
Depletion of guanine nucleotides leads to the Mdm2-dependent proteasomal degradation of nucleostemin.
2009 Apr 1
A phase I dose-ranging study of the pharmacokinetics, pharmacodynamics, safety, and tolerability of AVN944, an IMPDH inhibitor, in healthy male volunteers.
2009 Jan
Gateways to clinical trials.
2009 Mar

Sample Use Guides

In Vivo Use Guide
Pancreatic Cancer: patients took 150, 200, 250, 300, or 400 mg q12h. Advanced Stage Solid Tumors: 150 mg twice per day escalating to 750 mg twice per day.
Route of Administration: Oral
In Vitro Use Guide
CCRF-CEM, K562, and Raji cells were plated in 0.5 ml aliquots of growth medium into 48-well plates at 2×10(4) cells per well and then incubated with various concentrations of AVN-944 (1-10 uM). In cell proliferation the IC50s ranged from 0.13 to 0.16 uM for AVN-944.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:55:40 GMT 2023
Edited
by admin
on Fri Dec 15 15:55:40 GMT 2023
Record UNII
I3NPL1V48Q
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AVN-944
Common Name English
AVN 944
Code English
AVN944
Code English
AVN 944 [WHO-DD]
Common Name English
CARBAMIC ACID, N-((1S)-1-(3-((((3-METHOXY-4-(5-OXAZOLYL)PHENYL)AMINO)CARBONYL)AMINO)PHENYL)ETHYL)-, (1R)-1-(CYANOMETHYL)PROPYL ESTER
Common Name English
CARBAMIC ACID, ((1S)-1-(3-((((3-METHOXY-4-(5-OXAZOLYL)PHENYL)AMINO)CARBONYL)AMINO)PHENYL)ETHYL)-, (1R)-1-(CYANOMETHYL)PROPYL ESTER
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2087
Created by admin on Fri Dec 15 15:55:40 GMT 2023 , Edited by admin on Fri Dec 15 15:55:40 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C49181
Created by admin on Fri Dec 15 15:55:40 GMT 2023 , Edited by admin on Fri Dec 15 15:55:40 GMT 2023
PRIMARY
FDA UNII
I3NPL1V48Q
Created by admin on Fri Dec 15 15:55:40 GMT 2023 , Edited by admin on Fri Dec 15 15:55:40 GMT 2023
PRIMARY
PUBCHEM
9918559
Created by admin on Fri Dec 15 15:55:40 GMT 2023 , Edited by admin on Fri Dec 15 15:55:40 GMT 2023
PRIMARY
CAS
297730-17-7
Created by admin on Fri Dec 15 15:55:40 GMT 2023 , Edited by admin on Fri Dec 15 15:55:40 GMT 2023
PRIMARY
EPA CompTox
DTXSID80183921
Created by admin on Fri Dec 15 15:55:40 GMT 2023 , Edited by admin on Fri Dec 15 15:55:40 GMT 2023
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DRUG BANK
DB05500
Created by admin on Fri Dec 15 15:55:40 GMT 2023 , Edited by admin on Fri Dec 15 15:55:40 GMT 2023
PRIMARY
NIH
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