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Details

Stereochemistry ACHIRAL
Molecular Formula C26H26F3N3O3
Molecular Weight 485.4981
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SONIDEGIB

SMILES

C[C@H]1CN(C[C@@H](C)O1)C2=NC=C(NC(=O)C3=C(C)C(=CC=C3)C4=CC=C(OC(F)(F)F)C=C4)C=C2

InChI

InChIKey=VZZJRYRQSPEMTK-CALCHBBNSA-N
InChI=1S/C26H26F3N3O3/c1-16-14-32(15-17(2)34-16)24-12-9-20(13-30-24)31-25(33)23-6-4-5-22(18(23)3)19-7-10-21(11-8-19)35-26(27,28)29/h4-13,16-17H,14-15H2,1-3H3,(H,31,33)/t16-,17+

HIDE SMILES / InChI

Molecular Formula C26H26F3N3O3
Molecular Weight 485.4981
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Sonidegib, also known as LDE225 and marketed as Odomzo, is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) developed as an anticancer agent by Novartis. It was approved by the FDA for treating basal cell carcinoma in July 2015 and is awaiting approval in the EU. The hedgehog pathway is involved in many human cancers. Sonidegib effectively inhibits the regulator called smoothened (Smo), preventing the hedgehog pathway from functioning. As a result, tumours that depend on the hedgehog pathway are unable to grow. Sonidegib is approved for use in the US and EU for treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred post surgery or radiation therapy. It is also approved for adult patients with BCC who are not eligible for surgery or radiation therapy.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.5 nM [IC50]
2.5 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ODOMZO
PubMed

PubMed

TitleDatePubMed
Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist.
2010 Jun 10
Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling.
2012 Nov 15
Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition.
2014 Jul
Patents

Sample Use Guides

In Vivo Use Guide
Recommended dose: 200 mg orally once daily taken on an empty stomach, at least 1 hour before or 2 hours after a meal.
Route of Administration: Oral
In Vitro Use Guide
Sonidegib inhibits TM3 luciferized cell line with 0.6 nM and 8 nM, at the presence of 1 nM and 25 nM Hh agonist Ag1.5, respectively.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:36:12 UTC 2019
Edited
by admin
on Mon Oct 21 23:36:12 UTC 2019
Record UNII
0RLU3VTK5M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SONIDEGIB
DASH   INN   USAN   WHO-DD  
INN   USAN  
Official Name English
(1,1'-BIPHENYL)-3-CARBOXAMIDE, N-(6-((2R,6S)-2,6-DIMETHYL-4-MORPHOLINYL)-3-PYRIDINYL)-2-METHYL-4'-(TRIFLUOROMETHOXY)-, REL-
Common Name English
LDE 225
Code English
SONIDEGIB [INN]
Common Name English
SONIDEGIB [WHO-DD]
Common Name English
NVP-LDE225
Code English
SONIDEGIB [USAN]
Common Name English
NVP-LDE 225
Code English
N-(6-((2R,6S)-2,6-DIMETHYLMORPHOLIN-4-YL)PYRIDIN-3-YL)-2-METHYL-4'-(TRIFLUOROMETHOXY)BIPHENYL-3-CARBOXAMIDE
Systematic Name English
N-(6-((CIS-2,6-DIMETHYLMORPHOLIN-4-YL)-3-PYRIDYL)-2-METHYL-3-(4-(TRIFLUOROMETHOXY)PHENYL)BENZAMIDE
Common Name English
LDE-225
Code English
LDE225
Code English
NVP-LDE-225
Code English
ERISMODEGIB
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2189
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
WHO-ATC L01XX48
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
FDA ORPHAN DRUG 468814
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
NDF-RT N0000184149
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
Code System Code Type Description
RXCUI
1659191
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY RxNorm
IUPHAR
8199
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
NDF-RT
N0000184148
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY Smoothened Receptor Antagonists [MoA]
ChEMBL
CHEMBL2105737
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
DRUG BANK
DB09143
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
LactMed
956697-53-3
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
CAS
956697-53-3
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
WIKIPEDIA
SONIDEGIB
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
EU-Orphan Drug
EU/3/09/697(WITHDRAWN)
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY Treatment of naevoid basal-cell carcinoma syndrome (Gorlin syndrome) 24/11/2009 Withdrawn
NCI_THESAURUS
C82385
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
PUBCHEM
24775005
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
INN
9394
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
EVMPD
SUB123432
Created by admin on Mon Oct 21 23:36:12 UTC 2019 , Edited by admin on Mon Oct 21 23:36:12 UTC 2019
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> NON-INDUCER
compared to positive controls
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> NON-INDUCER
compared to positive controls
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
metabolism by CYP3A4 (at least 29% of its overall metabolism); Ketoconazole(CYP 3A4 inhibition) increased sonidegib exposure 2.2-fold;Rifampin (CYP 3A4 induction) reduced exposure by 72%
TARGET -> INHIBITOR
IC50
METABOLIC ENZYME -> NON-INHIBITOR
No time dependent inhibition upto 50 micromolar
METABOLIC ENZYME -> INHIBITOR
Ki
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METABOLITE INACTIVE -> PARENT
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METABOLITE ACTIVE -> PARENT
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Biological Half-life PHARMACOKINETIC