Details
Stereochemistry | ACHIRAL |
Molecular Formula | C27H32ClN5O5 |
Molecular Weight | 542.026 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCN(CCOC2=CC(OC3CCOCC3)=C4C(NC5=C(Cl)C=CC6=C5OCO6)=NC=NC4=C2)CC1
InChI
InChIKey=OUKYUETWWIPKQR-UHFFFAOYSA-N
InChI=1S/C27H32ClN5O5/c1-32-6-8-33(9-7-32)10-13-35-19-14-21-24(23(15-19)38-18-4-11-34-12-5-18)27(30-16-29-21)31-25-20(28)2-3-22-26(25)37-17-36-22/h2-3,14-16,18H,4-13,17H2,1H3,(H,29,30,31)
Molecular Formula | C27H32ClN5O5 |
Molecular Weight | 542.026 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Saracatinib (AZD0530) is an oral, dual inhibitor of c-Src/Abl kinases initially developed by AstraZeneca for the treatment of cancer. The drug was tested for many neoplasms and reached phase III for ovarian cancer (in combination with paclitaxel), however without demonstrating any significant effect. Sarcatinib is also tested in patients with Alzheimer's Disease (Phase II). Its effect on Alzheimer's Disease patients is explained by inhibition of another kinase, Fyn, which is highly expressed in brain.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17064066 |
2.7 nM [IC50] | ||
Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17064066 |
30.0 nM [IC50] | ||
Target ID: CHEMBL1841 Sources: http://www.alzforum.org/therapeutics/saracatinib |
8.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse events |
---|---|---|
250 mg 1 times / day multiple, oral Highest studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: Page: p.4879 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.4879 |
DLT: Asthenia, Acute renal failure... Dose limiting toxicities: Asthenia (grade 3, 14.3%) Sources: Page: p.4879Acute renal failure (grade 3, 14.3%) Leukopenia (grade 3, 14.3%) Septic shock (grade 5, 14.3%) |
175 mg 1 times / day multiple, oral MTD Dose: 175 mg, 1 times / day Route: oral Route: multiple Dose: 175 mg, 1 times / day Sources: Page: 4879 |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: Page: 4879 |
|
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: Page: p.4879 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.4879 |
DLT: Respiratory failure, Febrile neutropenia... Dose limiting toxicities: Respiratory failure (grade 5, 14.3%) Sources: Page: p.4879Febrile neutropenia (grade 3, 14.3%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Acute renal failure | grade 3, 14.3% DLT |
250 mg 1 times / day multiple, oral Highest studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: Page: p.4879 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.4879 |
Asthenia | grade 3, 14.3% DLT |
250 mg 1 times / day multiple, oral Highest studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: Page: p.4879 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.4879 |
Leukopenia | grade 3, 14.3% DLT |
250 mg 1 times / day multiple, oral Highest studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: Page: p.4879 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.4879 |
Septic shock | grade 5, 14.3% DLT, Disc. AE |
250 mg 1 times / day multiple, oral Highest studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: Page: p.4879 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.4879 |
Febrile neutropenia | grade 3, 14.3% DLT |
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: Page: p.4879 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.4879 |
Respiratory failure | grade 5, 14.3% DLT, Disc. AE |
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: Page: p.4879 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.4879 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely [IC50 201.8 uM] | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/22623106/ |
no | |||
yes [IC50 0.072 uM] | ||||
yes [IC50 0.9 uM] | ||||
yes [IC50 46 uM] | ||||
yes [IC50 50 uM] | ||||
yes [IC50 57 uM] | ||||
yes [Inhibition 33 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/31931755/ |
yes | |||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely | ||||
likely | ||||
likely | ||||
likely | ||||
likely | ||||
likely | ||||
likely | ||||
major | ||||
minor | ||||
minor | ||||
minor | ||||
unlikely | ||||
weak | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Clinical development of SRC tyrosine kinase inhibitors in lung cancer. | 2006 May |
|
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. | 2006 Nov 2 |
|
The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells. | 2009 Apr |
|
Src as a therapeutic target in men with prostate cancer and bone metastases. | 2009 Feb |
|
The effect of the dual Src/Abl kinase inhibitor AZD0530 on Philadelphia positive leukaemia cell lines. | 2009 Feb 13 |
|
Novel dual Src/Abl inhibitors for hematologic and solid malignancies. | 2010 Aug |
|
Effects of the Src inhibitor saracatinib (AZD0530) on renal function in healthy subjects. | 2010 Jul |
|
Effects of the Src kinase inhibitor saracatinib (AZD0530) on bone turnover in healthy men: a randomized, double-blind, placebo-controlled, multiple-ascending-dose phase I trial. | 2010 Mar |
Patents
Sample Use Guides
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 16:04:07 UTC 2023
by
admin
on
Sat Dec 16 16:04:07 UTC 2023
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Record UNII |
9KD24QGH76
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1967
Created by
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FDA ORPHAN DRUG |
674218
Created by
admin on Sat Dec 16 16:04:08 UTC 2023 , Edited by admin on Sat Dec 16 16:04:08 UTC 2023
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NCI_THESAURUS |
C129825
Created by
admin on Sat Dec 16 16:04:08 UTC 2023 , Edited by admin on Sat Dec 16 16:04:08 UTC 2023
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Code System | Code | Type | Description | ||
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Saracatinib
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C48378
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DB11805
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379231-04-6
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9017
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WW-109
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DTXSID90191355
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CHEMBL217092
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9KD24QGH76
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10302451
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47458
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C515233
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SUB32253
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100000124441
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INHIBITOR
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SALT/SOLVATE -> PARENT |
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ACTIVE MOIETY |