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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H19FN6O2
Molecular Weight 406.413
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LORLATINIB

SMILES

C[C@H]1OC2=CC(=CN=C2N)C3=C(C#N)N(C)N=C3CN(C)C(=O)C4=C1C=C(F)C=C4

InChI

InChIKey=IIXWYSCJSQVBQM-LLVKDONJSA-N
InChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1

HIDE SMILES / InChI

Molecular Formula C21H19FN6O2
Molecular Weight 406.413
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Lorlatinib is an investigational medicine that inhibits the anaplastic lymphoma kinase (ALK) and ROS1 proto-oncogene. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors. Lorlatinib has in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on a) the prior use of crizotinib and at least one other ALK inhibitor for metastatic disease, or b) the prior use of alectinib as the first ALK inhibitor therapy for metastatic disease, or c) the prior use of certinib as the first ALK inhibitor therapy for metastatic disease.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Tackling ALK in non-small cell lung cancer: the role of novel inhibitors.
2016 Jun
Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer.
2016 Oct
The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN.
2016 Sep 1
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dosage is 100 mg orally once daily.
Route of Administration: Oral
In Vitro Use Guide
Mutant ALKG1128A, ALKF1174L, ALKR1192P, ALKF1245C and ALKR1275Q responded to PF-06463922 with IC50 values similar to that of wild-type, two mutants – ALKI1171N and ALKY1278S – were more resistant, with 4- and 2.8-fold (3.21 nM and 2.27 nM) respectively of the IC50 of wild-type ALK kinase.
Substance Class Chemical
Created
by admin
on Tue Mar 06 11:01:57 UTC 2018
Edited
by admin
on Tue Mar 06 11:01:57 UTC 2018
Record UNII
OSP71S83EU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LORLATINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
LORLATINIB [WHO-DD]
Common Name English
PF-06463922
Code English
LORLATINIB [INN]
Common Name English
(10R)-7-AMINO-12-FLUORO-2,10,16-TRIMETHYL-15-OXO-10,15,16,17-TETRAHYDRO-2H-4,8- METHENOPYRAZOLO(4,3-H)(2,5,11)BENZOXADIAZACYCLOTETRADECINE-3-CARBONITRILE
Systematic Name English
LORLATINIB [USAN]
Common Name English
2H-4,8-METHENOPYRAZOLO(4,3-H)(2,5,11)BENZOXADIAZACYCLOTETRADECINE-3-CARBONITRILE, 7-AMINO-12-FLUORO-10,15,16,17-TETRAHYDRO-2,10,16-TRIMETHYL-15-OXO-, (10R)-
Systematic Name English
Code System Code Type Description
CAS
1454846-35-5
Created by admin on Tue Mar 06 11:01:57 UTC 2018 , Edited by admin on Tue Mar 06 11:01:57 UTC 2018
PRIMARY
NCI_THESAURUS
C113655
Created by admin on Tue Mar 06 11:01:57 UTC 2018 , Edited by admin on Tue Mar 06 11:01:57 UTC 2018
PRIMARY
INN
10278
Created by admin on Tue Mar 06 11:01:57 UTC 2018 , Edited by admin on Tue Mar 06 11:01:57 UTC 2018
PRIMARY
PUBCHEM
71731823
Created by admin on Tue Mar 06 11:01:57 UTC 2018 , Edited by admin on Tue Mar 06 11:01:57 UTC 2018
PRIMARY SWITZERF
ChEMBL
CHEMBL3286830
Created by admin on Tue Mar 06 11:01:57 UTC 2018 , Edited by admin on Tue Mar 06 11:01:57 UTC 2018
PRIMARY
EVMPD
SUB181272
Created by admin on Tue Mar 06 11:01:57 UTC 2018 , Edited by admin on Tue Mar 06 11:01:57 UTC 2018
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY