Details
Stereochemistry | ACHIRAL |
Molecular Formula | C27H32ClN5O5.2C4H4O4 |
Molecular Weight | 774.171 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 2 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.CN1CCN(CCOC2=CC(OC3CCOCC3)=C4C(NC5=C6OCOC6=CC=C5Cl)=NC=NC4=C2)CC1
InChI
InChIKey=OQXMMAQEMJUIQM-LVEZLNDCSA-N
InChI=1S/C27H32ClN5O5.2C4H4O4/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;2*5-3(6)1-2-4(7)8/h2-3,14-16,18H,4-13,17H2,1H3,(H,29,30,31);2*1-2H,(H,5,6)(H,7,8)/b;2*2-1+
Molecular Formula | C4H4O4 |
Molecular Weight | 116.0722 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
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 |
---|---|---|
Cooperative action of tamoxifen and c-Src inhibition in preventing the growth of estrogen receptor-positive human breast cancer cells. | 2006 Dec |
|
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 |
|
Research provides new hope for tamoxifen-resistant breast cancer patients. | 2008 Mar |
|
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 |
|
Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. | 2009 Jun |
|
Inhibition of Src with AZD0530 reveals the Src-Focal Adhesion kinase complex as a novel therapeutic target in papillary and anaplastic thyroid cancer. | 2009 Jun |
|
Antitumor effects and biomarkers of activity of AZD0530, a Src inhibitor, in pancreatic cancer. | 2009 Jun 15 |
|
A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: a California Cancer Consortium study. | 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 |
Patents
Sample Use Guides
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:56:24 UTC 2023
by
admin
on
Fri Dec 15 15:56:24 UTC 2023
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Record UNII |
8R1DYT4EAW
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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 |
C129825
Created by
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NCI_THESAURUS |
C1967
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admin on Fri Dec 15 15:56:24 UTC 2023 , Edited by admin on Fri Dec 15 15:56:24 UTC 2023
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SUB91845
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WW-110
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CHEMBL217092
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44195703
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8R1DYT4EAW
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DTXSID101008759
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C95224
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893428-72-3
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100000141455
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PARENT -> SALT/SOLVATE | |||
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |