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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H32N6O
Molecular Weight 432.5612
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NVP-LEQ-506

SMILES

C[C@@H]1CN(CCN1C2=CN=C(C=N2)C(C)(C)O)C3=NN=C(CC4=CC=CC=C4)C(C)=C3C

InChI

InChIKey=POERAARDVFVDLO-QGZVFWFLSA-N
InChI=1S/C25H32N6O/c1-17-16-30(11-12-31(17)23-15-26-22(14-27-23)25(4,5)32)24-19(3)18(2)21(28-29-24)13-20-9-7-6-8-10-20/h6-10,14-15,17,32H,11-13,16H2,1-5H3/t17-/m1/s1

HIDE SMILES / InChI
Molecular Formula C25H32N6O
Molecular Weight 432.5612
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

NPV-LEQ506 is an orally bioavailable small-molecule Smoothened (Smo) antagonist with potential antineoplastic activity. NPV-LEQ506 selectively binds to the Hedgehog (Hh)-ligand cell surface receptor Smo, which may result in the suppression of the Hh signaling pathway, thereby inhibiting tumor cell growth. NPV-LEQ506 is a second-generation inhibitor of smoothened (Smo) with IC50s of 2 and 4 nM in human and mouse, respectively. NPV-LEQ506 has been in clinical trials with Novartis studying the treatment of advanced solid tumors, recurrent or refractory medulloblastoma, and locally advanced or metastatic basal cell carcinoma.

CNS Activity

CNS Penetrant
2554
Curator's Comment: The compound is able to penetrate the blood–brain barrier as indicated by a brain/plasma AUC0–1 ratio of 0.69 after a single dose of 20 mg/kg in mice, which is an important requirement for treating brain tumors.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 7.52 null [pIC50]
PubMed

PubMed

TitleDatePubMed

Sample Use Guides

In Vivo Use Guide
The mice were treated orally (40 mg/kg) with NPV-LEQ506 for eight days.
Route of Administration: Oral
In Vitro Use Guide
NPV-LEQ506 is a second-generation inhibitor of smoothened (Smo) with IC50s of 2 and 4 nM in human and mouse, respectively.
Substance Class Chemical
Created
by admin
on Sat Dec 16 04:48:48 UTC 2023
Edited
by admin
on Sat Dec 16 04:48:48 UTC 2023
Record UNII
6SJX1T5HJD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NVP-LEQ-506
Common Name English
LEQ-506
Code English
LEQ506
Code English
2-PYRAZINEMETHANOL, 5-((2R)-4-(4,5-DIMETHYL-6-(PHENYLMETHYL)-3-PYRIDAZINYL)-2-METHYL-1-PIPERAZINYL)-.ALPHA.,.ALPHA.-DIMETHYL-
Systematic Name English
NVP-LEQ506
Code English
LEQ 506 [WHO-DD]
Common Name English
Code System Code Type Description
CAS
1204975-42-7
Created by admin on Sat Dec 16 04:48:48 UTC 2023 , Edited by admin on Sat Dec 16 04:48:48 UTC 2023
PRIMARY
NCI_THESAURUS
C91089
Created by admin on Sat Dec 16 04:48:48 UTC 2023 , Edited by admin on Sat Dec 16 04:48:48 UTC 2023
PRIMARY
SMS_ID
300000041551
Created by admin on Sat Dec 16 04:48:48 UTC 2023 , Edited by admin on Sat Dec 16 04:48:48 UTC 2023
PRIMARY
DRUG BANK
DB12857
Created by admin on Sat Dec 16 04:48:48 UTC 2023 , Edited by admin on Sat Dec 16 04:48:48 UTC 2023
PRIMARY
PUBCHEM
45100669
Created by admin on Sat Dec 16 04:48:48 UTC 2023 , Edited by admin on Sat Dec 16 04:48:48 UTC 2023
PRIMARY
FDA UNII
6SJX1T5HJD
Created by admin on Sat Dec 16 04:48:48 UTC 2023 , Edited by admin on Sat Dec 16 04:48:48 UTC 2023
PRIMARY
ChEMBL
CHEMBL3133037
Created by admin on Sat Dec 16 04:48:48 UTC 2023 , Edited by admin on Sat Dec 16 04:48:48 UTC 2023
PRIMARY
Related Record Type Details
SMOOTHENED HOMOLOG
TARGET -> INHIBITOR
Related Record Type Details
Structure of NVP-LEQ-506
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