AZD-1480

Investigational

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23847256
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase JAK2 59 Target ID: CHEMBL1075225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19962667	Inhibitor 8504		0.26 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Primary myelofibrosis 10 Sources: https://clinicaltrials.gov/ct2/show/NCT00910728	Primary	Phase I 438	Unknown Approved Use Unknown
Post-polycythaemia vera 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00910728	Primary	Phase I 438	Unknown Approved Use Unknown
Essential thrombocythemia 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00910728	Primary	Phase I 438	Unknown Approved Use Unknown
Hepatocellular carcinoma 83 Sources: https://clinicaltrials.gov/ct2/show/NCT01219543	Primary	Phase I 438	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
57.6 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21138246	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21138246	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

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677143	yes

PubMed

Title	Date	PubMed
Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases tumor growth in Neuroblastoma and Pediatric Sarcomas In vitro and In vivo.	2013-03	23531921

Patents

Sample Use Guides

In Vivo Use Guide

Thirty-eight patients with advanced malignancies were treated at doses of 10–70mgonce daily (QD) and 20–45 mg b.i.d. .

Route of Administration: Oral

In Vitro Use Guide

LN-17 cells were treated for 24 h with AZD1480 (0.05-1mkM) to determine whether Jak2 blockade can abrogate IL-6 dependent survival. Dose-dependent inhibition of pStat3Tyr705 and Stat3 DNA binding activity was observed in response to the addition of AZD1480, as was a loss of viability.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:51:33 GMT 2025` Edited by `admin` on `Mon Mar 31 20:51:33 GMT 2025`
Record UNII	KL2Z2TLF01
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AZD1480

Preferred Name

English

AZD-1480

Common Name

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