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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
Structure of MILCICLIB

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)

HIDE SMILES / InChI

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

Description
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.

Approval Year

TargetsConditions

Conditions

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
Patents

Sample Use Guides

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
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 Sat Jun 26 03:43:42 UTC 2021
Edited
by admin
on Sat Jun 26 03:43:42 UTC 2021
Record UNII
688000M8S8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MILCICLIB
INN  
INN  
Official Name English
PHA-848125
Code English
1H-PYRAZOLO(4,3-H)QUINAZOLINE-3-CARBOXAMIDE, 4,5-DIHYDRO-N,1,4,4-TETRAMETHYL-8-((4-(4-METHYL-1-PIPERAZINYL)PHENYL)AMINO)-
Systematic Name English
PHA 848125
Code English
MILCICLIB [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2185
Created by admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL564829
Created by admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
PRIMARY
EPA CompTox
802539-81-7
Created by admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
PRIMARY
PUBCHEM
16718576
Created by admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
PRIMARY
INN
9443
Created by admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
PRIMARY
FDA UNII
688000M8S8
Created by admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
PRIMARY
CAS
802539-81-7
Created by admin on Sat Jun 26 03:43:42 UTC 2021 , Edited by admin on Sat Jun 26 03:43:42 UTC 2021
PRIMARY
NCI_THESAURUS
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
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> NON-SUBSTRATE
high stability to human CYP4503A4 (85% remaining)
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY