NVP-LEQ-506

Investigational

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23821351 | https://www.ncbi.nlm.nih.gov/pubmed/22177102 | https://adisinsight.springer.com/drugs/800033722

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Smoothened homolog 20 Target ID: CHEMBL5971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27069629	Antagonist 2849		7.52 null [pIC50]

PubMed

Title	Date	PubMed
Molecular modeling study on resistance of WT/D473H SMO to antagonists LDE-225 and LEQ-506.	2018-03	29175550
Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model.	2016-04	27069629
Emerging treatments and signaling pathway inhibitors.	2011-12	22177102

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 `Mon Mar 31 21:23:47 GMT 2025` Edited by `admin` on `Mon Mar 31 21:23:47 GMT 2025`
Record UNII	6SJX1T5HJD
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NVP-LEQ-506

Common Name

English

LEQ-506

Preferred Name

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