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Details

Stereochemistry ABSOLUTE
Molecular Formula C14H14ClFN8
Molecular Weight 348.766
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AZD-1480

SMILES

C[C@H](NC1=NC=C(Cl)C(NC2=NNC(C)=C2)=N1)C3=NC=C(F)C=N3

InChI

InChIKey=PDOQBOJDRPLBQU-QMMMGPOBSA-N
InChI=1S/C14H14ClFN8/c1-7-3-11(24-23-7)21-13-10(15)6-19-14(22-13)20-8(2)12-17-4-9(16)5-18-12/h3-6,8H,1-2H3,(H3,19,20,21,22,23,24)/t8-/m0/s1

HIDE SMILES / InChI

Molecular Formula C14H14ClFN8
Molecular Weight 348.766
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19962667 | https://www.ncbi.nlm.nih.gov/pubmed/25504635

AZD1480 is a novel agent that inhibits Janus-associated kinases 1 and 2 (JAK1 and JAK2). In phase I study, AZD1480 was administered as an oral QD or b.i.d. monotherapy to patients with advanced solid tumors at eight dose levels in the ranges of 10–70 mg QD and 20–45 mg b.i.d. using a standard 3+3 design. AZD1480 had fast absorption, fast elimination, and dose-dependent increase in exposure from 10 mg to 50 mg. Unusual toxicity profile and overall lack of clinical activity led to discontinuation of development of AZD1480.

CNS Activity

Curator's Comment: In rats, AZD1480 had good blood-brain barrier penetration with a brain-to-blood ratio of 0.5.

Approval Year

AUC

AUC

ValueDoseCo-administeredAnalytePopulation
57.6 μM × h
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-1480 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2 h
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-1480 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2.
2008 Nov 21
Discovery of 5-chloro-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the Jak/Stat pathway.
2011 Jan 13
Potent and selective phosphopeptide mimetic prodrugs targeted to the Src homology 2 (SH2) domain of signal transducer and activator of transcription 3.
2011 May 26
Patents

Sample Use Guides

AZD-1480 was administered as an oral QD or b.i.d. monotherapy to patients with advanced solid tumors at eight dose levels in the ranges of 10–70 mg QD and 20– 45 mg b.i.d. using a standard 3 3 design.
Route of Administration: Oral
AZD-1480 at low doses (0.1–1 uM) inhibited constitutive STATs phosphorylation in HL cell lines, demonstrating immunoregulatory effects as it downregulated the surface expression of the STAT3-target immunosuppressive cell-surface protein PD-L1 and PD-L2, in addition to downregulation of IL-13, IL-6 and TARC. At higher concentration (5 uM), AZD-1480 induced antiproliferative effects in HL cell lines in a JAK/ STAT-independent manner.
Substance Class Chemical
Created
by admin
on Thu Jul 06 07:46:10 UTC 2023
Edited
by admin
on Thu Jul 06 07:46:10 UTC 2023
Record UNII
KL2Z2TLF01
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AZD-1480
Common Name English
AZD1480
Code English
2,4-PYRIMIDINEDIAMINE, 5-CHLORO-N2-((1S)-1-(5-FLUORO-2-PYRIMIDINYL)ETHYL)-N4-(5-METHYL-1H-PYRAZOL-3-YL)-
Systematic Name English
AZD 1480 [WHO-DD]
Common Name English
Code System Code Type Description
FDA UNII
KL2Z2TLF01
Created by admin on Thu Jul 06 07:46:10 UTC 2023 , Edited by admin on Thu Jul 06 07:46:10 UTC 2023
PRIMARY
SMS_ID
100000175287
Created by admin on Thu Jul 06 07:46:10 UTC 2023 , Edited by admin on Thu Jul 06 07:46:10 UTC 2023
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DRUG BANK
DB12588
Created by admin on Thu Jul 06 07:46:10 UTC 2023 , Edited by admin on Thu Jul 06 07:46:10 UTC 2023
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ChEMBL
CHEMBL1231124
Created by admin on Thu Jul 06 07:46:10 UTC 2023 , Edited by admin on Thu Jul 06 07:46:10 UTC 2023
PRIMARY
NCI_THESAURUS
C91394
Created by admin on Thu Jul 06 07:46:10 UTC 2023 , Edited by admin on Thu Jul 06 07:46:10 UTC 2023
PRIMARY
PUBCHEM
16659841
Created by admin on Thu Jul 06 07:46:10 UTC 2023 , Edited by admin on Thu Jul 06 07:46:10 UTC 2023
PRIMARY
EPA CompTox
DTXSID50239469
Created by admin on Thu Jul 06 07:46:10 UTC 2023 , Edited by admin on Thu Jul 06 07:46:10 UTC 2023
PRIMARY
CAS
935666-88-9
Created by admin on Thu Jul 06 07:46:10 UTC 2023 , Edited by admin on Thu Jul 06 07:46:10 UTC 2023
PRIMARY
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ACTIVE MOIETY