Lorlatinib (PF-6463922) - Moligand™, 10mM in DMSO , EML4-ALK inhibitor, CAS No.1454846-35-5, EML4-ALK inhibitor

CAS: 1454846-35-5 Cat. No.: L409078 Peso molecular: 406.41 Número EC: 813-704-5 PubChem CID: 71731823

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

(10R)-7-amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-2H-4,8-methenopyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

Lorlatinib (PF-6463922) Lorlatinib (PF-6463922) is a potent, dual ALK/ROS1 inhibitor with K i of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis . Phase 1.
In vitro

PF-06463922 demonstrates significant cell activity against ALK and a large set of ALK clinical mutations with IC50 ranging from 0.2 nM-77 nM. PF-06463922 significantly inhibits cell proliferation and induces cell apoptosis in the HCC78 human NSCLC cells harboring SLC34A2-ROS1 fusions and the BaF3-CD74-ROS1 cells expressing human CD74-ROS1.PF-06463922 also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions.

In vivo

In rats, PF-06463922 displays low plasma clearance, a moderate volume of distribution, a reasonable half-life, low propensity for p-glycoprotein 1-mediated efflux and a bioavailability of 100%. In vivo, PF-06463922 shows cytoreductive antitumor efficacy in the NIH3T3 xenograft models expressing human CD74-ROS1 and Fig-ROS1 via inhibition in ROS1 phosphorylation and the downstream signaling molecules, as well as inhibition of the cell cycle protein Cyclin D1 in tumors. In vivo, PF-06463922 also demonstrates marked antitumor activity in mice bearing tumor xenografts expressing EML4-ALK, EML4-ALK-L1196M, EML4-ALK-G1269A, EML4-ALK-G1202R or NPM-ALK.
Cell Data

cell lines：

Concentrations：

Incubation Time：

Powder Purity:≥99%

Specifications

Sinónimos

(10R)-7-amino-12-fluoro-10, 15, 16, 17-tetrahydro-2, 10, 16-trimethyl-15-oxo-2H-4, 8-methenopyrazolo[4, 3-h][2, 5, 11]benzoxadiazacyclotetradecine-3-carbonitrile

Especificaciones y pureza

Moligand™, 10mM in DMSO

Mecanismos bioquímicos y fisiológicos

Lorlatinib (PF-6463922) is a potent, dual ALK/ROS1 inhibitor with K_i of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis. Phase 1.

Condiciones de almacenamiento de almacenamiento

Store at -80°C

Enviado en

Dry ice packs + Cold packs

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Grado

Moligand™

Tipo de acción

INHIBITOR

Mecanismo de acción

EML4-ALK inhibitor

Propiedades del producto

• ALogP: 1.5

Nombres e identificadores

• Isómeros SMILES: C[C@@H]1C2=C(C=CC(=C2)F)C(=O)N(CC3=NN(C(=C3C4=CC(=C(N=C4)N)O1)C#N)C)C
• PubChem CID: 71731823
• Peso molecular: 406.41

Objetivos asociados (humanos)

PTK2 Tclin Focal adhesion kinase 1 (1 Activities)

Discover Target: PTK2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ROS1 Tclin Proto-oncogene tyrosine-protein kinase ROS (3 Activities)

Discover Target: ROS1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FER Tclin Tyrosine-protein kinase Fer (1 Activities)

Discover Target: FER

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FES Tclin Tyrosine-protein kinase Fes/Fps (2 Activities)

Discover Target: FES

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PTK2B Tclin Protein-tyrosine kinase 2-beta (1 Activities)

Discover Target: PTK2B

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

LTK Tclin Leukocyte tyrosine kinase receptor (1 Activities)

Discover Target: LTK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

TNK2 Tclin Activated CDC42 kinase 1 (1 Activities)

Discover Target: TNK2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ALK Tclin ALK tyrosine kinase receptor (13 Activities)

Discover Target: ALK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

NTRK2 Tclin BDNF/NT-3 growth factors receptor (2 Activities)

Discover Target: NTRK2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

NTRK1 Tclin High affinity nerve growth factor receptor (1 Activities)

Discover Target: NTRK1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Referencias

1. Ye Zhongjiang, Wang Chenxiang, Li Rongqi, Chen Chuang, Yang Jianhui, Chen Yizhang, Fu Jing, Zhou Tao, Jin Mi, Huang Aifang, Zhang Xiuhua, Zhou Ziye.  (2023)  Potential interactions between triazole antifungal agents and lorlatinib based on ultra-performance liquid chromatography-tandem mass spectrometry in rat plasma.  JOURNAL OF PHARMACY AND PHARMACOLOGY,  76  (2): (115-121).  [PMID:38150242] [10.1093/jpp/rgad105]

2. Cong Xie, Tongshu Guan, Jin Huang, Jiayu Chen, Yilei Li, Ping Zheng.  (2025)  Cyp3a4-Mediated in vitro Metabolism and in vivo Disposition of Lorlatinib in Rats.  Drug Design Development and Therapy,      [PMID:41169706] [10.2147/DDDT.S565228]