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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H27Cl2FN6O3
Molecular Weight 561.435
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENSARTINIB

SMILES

C[C@@H](OC1=CC(=NN=C1N)C(=O)NC2=CC=C(C=C2)C(=O)N3C[C@H](C)N[C@H](C)C3)C4=C(Cl)C=CC(F)=C4Cl

InChI

InChIKey=GLYMPHUVMRFTFV-QLFBSQMISA-N
InChI=1S/C26H27Cl2FN6O3/c1-13-11-35(12-14(2)31-13)26(37)16-4-6-17(7-5-16)32-25(36)20-10-21(24(30)34-33-20)38-15(3)22-18(27)8-9-19(29)23(22)28/h4-10,13-15,31H,11-12H2,1-3H3,(H2,30,34)(H,32,36)/t13-,14+,15-/m1/s1

HIDE SMILES / InChI
X-396 (Ensartinib) is a novel, potent anaplastic lymphoma kinase (ALK) small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. Ensartinib has demonstrated activity in ALK treatment naïve and previously treated patients and has a generally well tolerated safety profile. Ensartinib is currently in a global phase 3 trial in ALK positive non-small cell lung cancer (NSCLC) patients. The phase 1/2 clinical findings support the preclinical results that the use of ensartinib may result in favorable therapeutic outcomes in patients with ALK NSCLC, including patients with CNS metastases. In this study, ensartinib was generally well tolerated with the most common adverse event being a rash.

CNS Activity

Curator's Comment: Preclinical data demonstrated that X-396 penetrates the blood-brain barrier in mice.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
318 ng/mL
225 mg 1 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
X-396 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
311 ng/mL
225 mg 1 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
X-396 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
212 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
X-396 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5530 ng × h/mL
225 mg 1 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
X-396 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5330 ng × h/mL
225 mg 1 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
X-396 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
3827 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
X-396 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
33.2 h
225 mg 1 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
X-396 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
37.7 h
225 mg 1 times / day multiple, oral
dose: 225 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
X-396 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
18.3 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
X-396 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
8.45%
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
X-396 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
likely [IC50 >50 uM]
moderate [IC50 14.6 uM]
moderate [IC50 19.1 uM]
moderate [IC50 20.6 uM]
no
no
no
no
no
no
no
no
no
yes [IC50 1.12 uM]
yes [IC50 3.69 uM]
yes [IC50 4.93 uM]
yes [IC50 9.13 uM]
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes
PubMed

PubMed

TitleDatePubMed
Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors.
2011 Jul 15
Patents

Sample Use Guides

Eligible patients with ALK+ NSCLC will receive oral X-396 (ensartinib) at 225mg QD with or without food until progression or unacceptable toxicity develops
Route of Administration: Oral
X-396 inhibited endogenous ALK phosphorylation and potential downstream signaling pathways in H3122 lung cancer cells harboring the EML4-ALK E13;A20 fusion at low concentrations of drug (100-1000 nM).
Name Type Language
ENSARTINIB
INN   WHO-DD  
INN   USAN  
Official Name English
3-PYRIDAZINECARBOXAMIDE, 6-AMINO-5-((1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY)-N-(4-(((3R,5S)-3,5-DIMETHYL-1-PIPERAZINYL)CARBONYL)PHENYL)
Preferred Name English
ENSARTINIB [USAN]
Common Name English
ensartinib [INN]
Common Name English
X-396
Code English
6-AMINO-5-((1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY)- N-(4-((3R,5S)-3,5-DIMETHYLPIPERAZINE- 1-CARBONYL)PHENYL)PYRIDAZINE-3-CARBOXAMIDE
Systematic Name English
Ensartinib [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
NCI_THESAURUS C141136
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
Code System Code Type Description
SMS_ID
100000174627
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
PRIMARY
USAN
EF-132
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
PRIMARY
CAS
1370651-20-9
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
PRIMARY
PUBCHEM
56960363
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
PRIMARY
DRUG BANK
DB14860
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
PRIMARY
INN
10339
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
PRIMARY
NCI_THESAURUS
C102754
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
PRIMARY
FDA UNII
SMA5ZS5B22
Created by admin on Tue Apr 01 16:41:22 GMT 2025 , Edited by admin on Tue Apr 01 16:41:22 GMT 2025
PRIMARY