Lorlatinib

Entry

D11012                      Drug

Name

Lorlatinib (JAN/USAN/INN);
Lorbrena (TN)

Product

LORBRENA (Pfizer Laboratories Div Pfizer)

Formula

C21H19FN6O2

Exact mass

406.1554

Mol weight

406.413

Structure

Class

Antineoplastic
DG01918  Tyrosine kinase inhibitor
  DG03136  ALK inhibitor
Metabolizing enzyme substrate
DG01633  CYP3A/CYP3A4 substrate
Metabolizing enzyme inducer
DG02853  CYP3A/CYP3A4 inducer
Transporter inducer
DG01893  ABCB1 inducer

Remark

Therapeutic category:

4291

ATC code:

L01ED05

Product:

D11012<JP/US>

Efficacy

Antineoplastic, Tyrosine kinase inhibitor

Disease

Non-small cell lung cancer (ALK positive) [DS:H00014]

Target

EML4-ALK [HSA_VAR:238v2] [HSA:238] [KO:K05119]
ALK (CD246) [HSA:238] [KO:K05119]
ROS1 [HSA:6098] [KO:K05088]

Network

N10004

Second/third-generation tyrosine kinase inhibitor to ALK fusion

Pathway

hsa05200

Pathways in cancer

hsa05223

Non-small cell lung cancer

Metabolism

Enzyme: CYP3A [HSA:1576 1577 1551]

Interaction

CYP induction: CYP3A [HSA:1576 1577 1551]
Transporter induction: ABCB1 [HSA:5243]

Brite

Anatomical Therapeutic Chemical (ATC) classification [BR:br08303]
L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
  L01 ANTINEOPLASTIC AGENTS
   L01E PROTEIN KINASE INHIBITORS
    L01ED Anaplastic lymphoma kinase (ALK) inhibitors
     L01ED05 Lorlatinib
      D11012  Lorlatinib (JAN/USAN/INN) <JP/US>
USP drug classification [BR:br08302]
Antineoplastics
  Molecular Target Inhibitors
   Lorlatinib
    D11012  Lorlatinib (JAN/USAN/INN)
Therapeutic category of drugs in Japan [BR:br08301]
4  Agents affecting cellular function
  42  Antineoplastics
   429  Miscellaneous
    4291  Other Antitumors
     D11012  Lorlatinib (JAN/USAN/INN)
Drug groups [BR:br08330]
Antineoplastic
  DG01918  Tyrosine kinase inhibitor
   DG03136  ALK inhibitor
    D11012  Lorlatinib
Metabolizing enzyme substrate
  DG01633  CYP3A/CYP3A4 substrate
   D11012  Lorlatinib
Metabolizing enzyme inducer
  DG02853  CYP3A/CYP3A4 inducer
   D11012  Lorlatinib
Transporter inducer
  DG01893  ABCB1 inducer
   D11012  Lorlatinib
Drug classes [BR:br08332]
Antineoplastic
  DG03136  ALK inhibitor
   D11012  Lorlatinib
Target-based classification of drugs [BR:br08310]
Protein kinases
  Receptor tyrosine kinases (RTK)
   INSR family
    ROS1
     D11012  Lorlatinib (JAN/USAN/INN) <JP/US>
   ALK family
    ALK (CD246)
     D11012  Lorlatinib (JAN/USAN/INN) <JP/US>
    EML4-ALK [HSA_VAR:238v2]
     D11012  Lorlatinib (JAN/USAN/INN) <JP/US>
New drug approvals in the USA [br08319.html]
New molecular entities and new therapeutic biological products
  D11012
New drug approvals in Europe [br08329.html]
European public assessment reports (EPAR) authorised medicine
  D11012
New drug approvals in Japan [br08318.html]
Drugs with new active ingredients
  D11012
New drug approvals in the USA, Europe and Japan [br08328.html]
Approval dates by FDA, EMA and PMDA
  D11012
Drug metabolizing enzymes and transporters [br08309.html]
Drug metabolizing enzymes
  D11012
Drug transporters
  D11012
Pharmacogenomic biomarkers [br08341.html]
Somatic variations in targeted cancer therapies
  D11012

Other DBs

CAS:	1454846-35-5

PubChem:

346930790

ChEBI:

143117

PDB-CCD:

5P8[PDBj]

KCF data

ATOM        30
            1   C8y C    18.0153  -18.0595
            2   C8y C    18.0153  -19.3981
            3   N5x N    19.1531  -20.0674
            4   C8x C    20.3579  -19.3981
            5   C8y C    20.3579  -18.0595
            6   C8x C    19.1531  -17.3902
            7   C8y C    21.4957  -17.3902
            8   O2x O    16.8775  -17.3902
            9   C1y C    16.8775  -16.0516
            10  C8y C    15.7397  -15.3823
            11  C8y C    22.7673  -17.7918
            12  N4y N    23.7105  -16.7209
            13  N5x N    22.7673  -15.5100
            14  C8y C    21.4957  -16.0516
            15  C1x C    19.6216  -15.3823
            16  C8y C    15.7397  -14.0437
            17  C8x C    14.6018  -13.3744
            18  C8x C    13.4640  -14.0437
            19  C8y C    13.4640  -15.3823
            20  C8x C    14.6018  -16.0516
            21  X   F    12.3262  -16.0516
            22  C5x C    17.7476  -13.3744
            23  N1y N    19.6216  -14.0437
            24  O5x O    17.7476  -12.0358
            25  C1a C    18.0395  -15.3870
            26  N1a N    16.8533  -20.0628
            27  C1a C    25.0491  -16.7209
            28  C3b C    23.1766  -19.0664
            29  N3a N    23.5231  -20.3594
            30  C1a C    20.7393  -13.2563
BOND        33
            1     1   2 2
            2     2   3 1
            3     3   4 2
            4     4   5 1
            5     5   6 2
            6     1   6 1
            7     5   7 1
            8     1   8 1
            9     8   9 1
            10    9  10 1
            11    7  11 2
            12   11  12 1
            13   12  13 1
            14   13  14 2
            15    7  14 1
            16   15  14 1
            17   10  16 2
            18   16  17 1
            19   17  18 2
            20   18  19 1
            21   19  20 2
            22   10  20 1
            23   19  21 1
            24   22  23 1
            25   22  16 1
            26   22  24 2
            27   23  15 1
            28    9  25 1 #Up
            29    2  26 1
            30   12  27 1
            31   11  28 1
            32   28  29 3
            33   23  30 1