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
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
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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/22829094 | https://www.ncbi.nlm.nih.gov/pubmed/23847256https://www.ncbi.nlm.nih.gov/pubmed/23847256Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22829094 | https://www.ncbi.nlm.nih.gov/pubmed/23847256https://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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23847256
Curator's Comment: In rats, AZD1480 had good blood-brain barrier penetration with a brain-to-blood ratio of 0.5.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2971 |
|||
Target ID: CHEMBL1075225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19962667 |
0.26 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
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 |
T1/2
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 |
PubMed
Title | Date | PubMed |
---|---|---|
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
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23847256
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22829094
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
Edited
Thu Jul 06 07:46:10 UTC 2023
by
admin
on
Thu Jul 06 07:46:10 UTC 2023
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Record UNII |
KL2Z2TLF01
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Record Status |
Validated (UNII)
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Record Version |
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