U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C27H34N4O5
Molecular Weight 494.5827
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NVP-TNKS-656

SMILES

COC1=CC=C(C=C1)C(=O)C2CCN(CC(=O)N(CC3CC3)CC4=NC(=O)C5=C(CCOC5)N4)CC2

InChI

InChIKey=DYGBNAYFDZEYBA-UHFFFAOYSA-N
InChI=1S/C27H34N4O5/c1-35-21-6-4-19(5-7-21)26(33)20-8-11-30(12-9-20)16-25(32)31(14-18-2-3-18)15-24-28-23-10-13-36-17-22(23)27(34)29-24/h4-7,18,20H,2-3,8-17H2,1H3,(H,28,29,34)

HIDE SMILES / InChI
Molecular Formula C27H34N4O5
Molecular Weight 494.5827
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

NVP-TNKS656 was identified as an orally active selective tankyrase 2 (TNKS2) inhibitor, which is also antagonist of Wnt pathway activity. On animal models for Colorectal Cancer was shown, that NVP-TNKS656 reduces nuclear β-catenin, reverts such resistance, and represses tumor growth.

Originator

Novartis
173
Curator's Comment: # Novartis Institutes for Biomedical Research, Inc

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 6.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor.
2013 Aug 22
Patents

Patents

US2015025070
1
US2016184310
1

Sample Use Guides

In Vivo Use Guide
MMTV-Wnt1 tumor bearing athymic nude mice: NVP-TNKS656: 350 mg/kg, p.o. mice bearing SW480 xenografts: twice daily with vehicle, NVP-TNKS656 (100 mg/kg, subcutaneous injection) or AZD6244 (45 mg/kg, oral) for the duration of the study.
Route of Administration: Other
In Vitro Use Guide
Combination with NVP-TNKS656 promoted apoptosis in PI3K or AKT inhibitor-resistant cells with high nuclear β-catenin content. High FOXO3A activity conferred sensitivity to NVP-TNKS656 treatment. Patient-derived cells were treated with NVP-TNKS656 100 nmol/L for 7 days and eGFP accumulation was measured by flow cytometry.
Substance Class Chemical
Created
by admin
on Sat Dec 16 20:12:19 GMT 2023
Edited
by admin
on Sat Dec 16 20:12:19 GMT 2023
Record UNII
YE73635MQC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NVP-TNKS-656
Code English
NVP-TNKS 656
Code English
NVP-TNKS656
Code English
N-(Cyclopropylmethyl)-4-(4-methoxybenzoyl)-N-[(3,5,7,8-tetrahydro-4-oxo-4H-pyrano[4,3-d]pyrimidin-2-yl)methyl]-1-piperidineacetamide
Systematic Name English
1-Piperidineacetamide, N-(cyclopropylmethyl)-4-(4-methoxybenzoyl)-N-[(3,5,7,8-tetrahydro-4-oxo-4H-pyrano[4,3-d]pyrimidin-2-yl)methyl]-
Systematic Name English
Code System Code Type Description
CAS
1419949-20-4
Created by admin on Sat Dec 16 20:12:19 GMT 2023 , Edited by admin on Sat Dec 16 20:12:19 GMT 2023
PRIMARY
FDA UNII
YE73635MQC
Created by admin on Sat Dec 16 20:12:19 GMT 2023 , Edited by admin on Sat Dec 16 20:12:19 GMT 2023
PRIMARY
PUBCHEM
136237316
Created by admin on Sat Dec 16 20:12:19 GMT 2023 , Edited by admin on Sat Dec 16 20:12:19 GMT 2023
PRIMARY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966