Details
Stereochemistry | ACHIRAL |
Molecular Formula | C25H32N8O |
Molecular Weight | 460.5755 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1(C)Cc2cnc(Nc3ccc(cc3)N4CCN(C)CC4)nc2-c5c1c(C(=NC)O)nn5C
InChI
InChIKey=RXZMYLDMFYNEIM-UHFFFAOYSA-N
InChI=1S/C25H32N8O/c1-25(2)14-16-15-27-24(29-20(16)22-19(25)21(23(34)26-3)30-32(22)5)28-17-6-8-18(9-7-17)33-12-10-31(4)11-13-33/h6-9,15H,10-14H2,1-5H3,(H,26,34)(H,27,28,29)
Molecular Formula | C25H32N8O |
Molecular Weight | 460.5755 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment:: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800026196 | http://www.tizianalifesciences.com/Thymic_Liver_Cancer.html | http://meetinglibrary.asco.org/content/131226-144 | https://www.ncbi.nlm.nih.gov/pubmed/22160853
Curator's Comment:: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800026196 | http://www.tizianalifesciences.com/Thymic_Liver_Cancer.html | http://meetinglibrary.asco.org/content/131226-144 | https://www.ncbi.nlm.nih.gov/pubmed/22160853
An orally bioavailable inhibitor of cyclin-dependent kinases (CDKs) and thropomyosin receptor kinase A (TRKA), with potential antineoplastic activity. CDK2/TRKA inhibitor PHA-848125 AC potently inhibits cyclin-dependent kinase 2 (CDK2) and exhibits activity against other CDKs including CDK1 and CDK4, in addition to TRKA. Inhibition of these kinases may result in cell cycle arrest and apoptosis of tumor cells that express these kinases. Milciclib is currently in phase II clinical trials for thymic carcinoma, glioma and liver cancer. The most common adverse events are nausea and asthenia, vomiting, myasthenic syndrome, dehydration, hypophosphatemia, cytolytic hepatitis and plantar fasciitis.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3038469 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19603809 |
45.0 nM [IC50] | ||
Target ID: CHEMBL1907601 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19603809 |
160.0 nM [IC50] | ||
Target ID: CHEMBL2094126 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19603809 |
363.0 nM [IC50] | ||
Target ID: CHEMBL1907600 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19603809 |
265.0 nM [IC50] | ||
Target ID: CHEMBL2094127 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19603809 |
398.0 nM [IC50] | ||
Target ID: CHEMBL2111288 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19603809 |
150.0 nM [IC50] | ||
Target ID: CHEMBL2815 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19603809 |
53.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23347136 |
Primary | Unknown Approved UseUnknown |
||
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. | 2009 Aug 27 |
|
Dual targeting of CDK and tropomyosin receptor kinase families by the oral inhibitor PHA-848125, an agent with broad-spectrum antitumor efficacy. | 2010 Aug |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01011439
150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19603809
The effects of compound Milciclib on the cell cycle progression and DNA synthesis were analyzed using flow cytometry analysis and BrdU incorporation, respectively, on A2780 ovarian carcinoma cells in exponential growth in the presence or absence of compound, for 24 h at 1 μM. At this concentration, the compound was able to show a clear reduction of S phase population, which was associated with an increase of G1 population as expected for a CDK2/cyclin A inhibitor.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Jun 26 03:43:42 UTC 2021
by
admin
on
Sat Jun 26 03:43:42 UTC 2021
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Record UNII |
688000M8S8
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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 |
C2185
Created by
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CHEMBL564829
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802539-81-7
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16718576
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9443
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688000M8S8
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802539-81-7
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admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
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C148410
Created by
admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
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Related Record | Type | Details | ||
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> NON-SUBSTRATE |
high stability to human CYP4503A4 (85% remaining)
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TARGET -> INHIBITOR |
IC50
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Related Record | Type | Details | ||
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ACTIVE MOIETY |