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)
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 |
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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 |
---|---|---|
Src family kinase oncogenic potential and pathways in prostate cancer as revealed by AZD0530. | 2008 Oct 23 |
|
The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells. | 2009 Apr |
|
Improved response by co-targeting EGFR/EGFRvIII and Src family kinases in human cancer cells. | 2009 Feb |
|
A novel Src kinase inhibitor reduces tumour formation in a skin carcinogenesis model. | 2009 Feb |
|
Quantification of focal adhesion kinase activation loop phosphorylation as a biomarker of Src activity. | 2009 Mar |
|
Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells. | 2009 May |
|
Combined Src and aromatase inhibition impairs human breast cancer growth in vivo and bypass pathways are activated in AZD0530-resistant tumors. | 2009 May 15 |
|
Gene array and fluorescence in situ hybridization biomarkers of activity of saracatinib (AZD0530), a Src inhibitor, in a preclinical model of colorectal cancer. | 2010 Aug 15 |
|
Effects of the Src inhibitor saracatinib (AZD0530) on renal function in healthy subjects. | 2010 Jul |
|
Effect of the specific Src family kinase inhibitor saracatinib on osteolytic lesions using the PC-3 bone model. | 2010 Jun |
|
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 |
|
Impact of the Src inhibitor saracatinib on the metastatic phenotype of a fibrosarcoma (KHT) tumor model. | 2010 Nov |
Patents
Sample Use Guides
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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
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NCI_THESAURUS |
C129825
Created by
admin on Sat Dec 16 16:04:08 GMT 2023 , Edited by admin on Sat Dec 16 16:04:08 GMT 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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ACTIVE MOIETY
SALT/SOLVATE (PARENT)