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Details

Stereochemistry ACHIRAL
Molecular Formula C19H12ClN3O2
Molecular Weight 349.77
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SILMITASERTIB

SMILES

OC(=O)C1=CC2=C(C=C1)C3=C(C=CN=C3)C(NC4=CC(Cl)=CC=C4)=N2

InChI

InChIKey=MUOKSQABCJCOPU-UHFFFAOYSA-N
InChI=1S/C19H12ClN3O2/c20-12-2-1-3-13(9-12)22-18-15-6-7-21-10-16(15)14-5-4-11(19(24)25)8-17(14)23-18/h1-10H,(H,22,23)(H,24,25)

HIDE SMILES / InChI

Molecular Formula C19H12ClN3O2
Molecular Weight 349.77
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 https://www.ncbi.nlm.nih.gov/pubmed/21159648

Silmitasertib (CX-4945) is a potent and selective orally bioavailable small molecule inhibitor of Casein kinase II (CK2). The antiproliferative activity of CX-4945 against cancer cells correlated with expression levels of the CK2α catalytic subunit. CX-4945 caused cell-cycle arrest and selectively induced apoptosis in cancer cells relative to normal cells. When administered orally in murine xenograft models, CX-4945 was well tolerated and demonstrated robust antitumor activity. Senhwa Biosciences is developing silmitasertib for the treatment of cholangiocarcinoma, other solid tumours, Castleman's disease (giant lymph node hyperplasia) and multiple myeloma. The compound was originally developed by Cylene Pharmaceuticals. Phase Ib/II development is underway in the US and South Korea for the treatment of cholangiocarcinoma, and development in the remaining indications is at the phase I stage. As at July 2016, no recent reports of development had been identified for phase-I development in Giant-lymph-node-hyperplasia in USA (PO, Capsule), phase-I development in Multiple-myeloma in USA (PO, Capsule), phase-I development in Solid-tumours (Late-stage disease) in USA (PO, Capsule).

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.0 nM [IC50]
1.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy.
2010 Dec 15
Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer.
2011 Jan 27
Patents

Sample Use Guides

Interim results of a phase I trial showed that silmitasertib was well-tolerated in patients with solid tumours. Thirteen such patients (3-4 patients per cohort, from four separate dose cohorts) received oral, twice-daily doses of silmitasertib for 21 consecutive days of a 4-week cycle. The trial design provided for administration of silmitasertib in successive dose cohorts at 90mg, 160mg, 300mg, 460mg, 700mg and 1000mg per dose. No adverse events of grade ≥3 were reported. No dose-limiting toxicities had been observed and the maximum tolerated dose was yet to be defined.
Route of Administration: Oral
Silmitasertib (CX-4945) exerts antiproliferative activity of in a panel of breast cancer cell lines with EC50 1.71-20.01 uM
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:41:59 GMT 2023
Edited
by admin
on Fri Dec 15 18:41:59 GMT 2023
Record UNII
C6RWP0N0L2
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SILMITASERTIB
INN   WHO-DD  
INN  
Official Name English
BENZO(C)-2,6-NAPHTHYRIDINE-8-CARBOXYLIC ACID, 5-((3-CHLOROPHENYL)AMINO)-
Common Name English
silmitasertib [INN]
Common Name English
Silmitasertib [WHO-DD]
Common Name English
CX4945
Code English
CX 4945
Code English
5-((3-CHLOROPHENYL)AMINO)BENZO(C)(2,6)NAPHTHYRIDINE-8-CARBOXYLIC ACID
Systematic Name English
CX-4945 FREE ACID
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1404
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
FDA ORPHAN DRUG 548516
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
FDA ORPHAN DRUG 856821
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
FDA ORPHAN DRUG 851021
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C129825
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
CONCEPT
PUBCHEM
24748573
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
WIKIPEDIA
Silmitasertib
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
SMS_ID
300000021749
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
CAS
1009820-21-6
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
DRUG BANK
DB15408
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
FDA UNII
C6RWP0N0L2
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
EPA CompTox
DTXSID40143602
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
ChEMBL
CHEMBL1230165
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
INN
9213
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
NCI_THESAURUS
C98054
Created by admin on Fri Dec 15 18:41:59 GMT 2023 , Edited by admin on Fri Dec 15 18:41:59 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
TARGET->WEAK INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
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ACTIVE MOIETY