ALK inhibitor 2 - CAS 761438-38-4
Not Intended for Therapeutic Use. For research use only.
Category:
Inhibitor
Product Name:
ALK inhibitor 2
Catalog Number:
761438-38-4
Synonyms:
Benzenesulfonamide, 2-[[5-chloro-2-[[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]amino]-4-pyrimidinyl]amino]-N-methyl-
CAS Number:
761438-38-4
Description:
ALK inhibitor 2 is a novel and selective inhibitor for the ALK kinase.
Molecular Weight:
518.03
Molecular Formula:
C23H28ClN7O3S
COA:
Inquire
MSDS:
Inquire
Targets:
ALK
Chemical Structure
CAS 761438-38-4 ALK inhibitor 2

Related ALK Products


IN-1130
(CAS: 868612-83-3)

IN-1130 is a selective ALK5 inhibitor with >100 fold selectivity over p38α and a panel of 26 other serine/threonine and tyrosine kinases. It also inhibit phosph...

CAS 1116235-97-2 GSK1838705A

GSK1838705A
(CAS: 1116235-97-2)

GSK1838705A is a small-molecule kinase inhibitor that inhibits IGF-IR and IR (insulin receptor) with IC50s of 2.0 and 1.6 nM, respectively. GSK1838705A blocks ...

CAS 1032900-25-6 Ceritinib

Ceritinib
(CAS: 1032900-25-6)

This active molecular is a selective inhibitor of ALK(anaplastic lymphoma kinase)which is a target found in NSCLC (metastatic non-small cell lung cancer). The I...

CAS 1062368-62-0 LDN-193189 HCl

LDN-193189 HCl
(CAS: 1062368-62-0)

LDN193189 HCl is the hydrochloride salt of LDN193189, which is a selective BMP signaling inhibitor, and inhibits the transcriptional activity of the BMP type I ...

CAS 1356962-20-3 AZD-3463

AZD-3463
(CAS: 1356962-20-3)

AZD-3463 is a potent ALK/IGF1R inhibitor with potential anticancer activity.

CAS 1256580-46-7 Alectinib

Alectinib
(CAS: 1256580-46-7)

Alectinib, also known as AF802, or CH5424802 or RO5424802, is a potent, selective, and orally available ALK inhibitor with a unique chemical scaffold, showing ...

CAS 1356962-34-9 HG-14-10-04

HG-14-10-04
(CAS: 1356962-34-9)

HG-14-10-04 is a potent and specific ALK inhibitor with IC50 of 20 nM.

CAS 1206711-16-1 DMH-1

DMH-1
(CAS: 1206711-16-1)

DMH-1 is a second-generation small molecule BMP inhibitor based on dorsomorphin. DMH-1 effectively inhibits the bone morphogenic protein (BMP) ALK2 receptor (IC...

Brigatinib (AP-26113)
(CAS: 1197953-54-0)

Brigatinib, is an orally active, also known as AP-26113, potent and selective Dual ALK/EGFR inhibitor. AP26113 binds to and inhibits ALK kinase(ALK belongs to t...

CAS 761439-42-3 TAE684

TAE684
(CAS: 761439-42-3)

NVP-TAE684 is a highly potent and selective small-molecule ALK inhibitor, which blocked the growth of ALCL-derived and ALK-dependent cell lines with IC(50) valu...

CAS 1197958-12-5 AP-26113

AP-26113
(CAS: 1197958-12-5)

AP26113 is an orally available inhibitor of receptor tyrosine kinases anaplastic lymphoma kinase (ALK) and the epidermal growth factor receptor (EGFR) with pote...

CAS 1454846-35-5 PF-06463922

PF-06463922
(CAS: 1454846-35-5)

PF-06463922 is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), wi...

CEP-14513
(CAS: 856693-04-4)

CEP-14513 is a ALK inhibitor. It shows ALK inhibitory activity in both in vitro enzymatic assay (IC50 = 5 nM) and cell-based assays of ALK tyrosine phosphorylat...

CAS 1431985-92-0 K02288

K02288
(CAS: 1431985-92-0)

K02288 is a highly selective 2-aminopyridinebased inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current le...

BAY-754

BAY-754 is an ALK-1 inhibitor used as an anti-angiogenesis agent. It inhibited the eye vascular leakage in dose manner in mouse model.

CAS 1062368-49-3 ML347

ML347
(CAS: 1062368-49-3)

ML347 is a selective BMP receptor inhibitor with IC50 of 32 nM for ALK2, >300-fold selectivity over ALK3. Also inhibits ALK1 activity with IC50 of 46 nM.

CAS 1432597-26-6 LDN-212854

LDN-212854
(CAS: 1432597-26-6)

LDN-212854 is a potent and selective BMP receptor inhibitor with IC50 of 1.3 nM for ALK2. LDN-212854 exhibits some selectivity for ALK2 in preference to other...

CAS 356559-13-2 SB-505124 hydrochloride

SB-505124 hydrochloride
(CAS: 356559-13-2)

SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptor ALK5 and as well as being a selective inhibitor of ALK4 but with less pote...

CAS 1391712-60-9 CEP-37440

CEP-37440
(CAS: 1391712-60-9)

CEP-37440 is an orally available dual kinase inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) and focal adhesion kinase (FAK), with po...

Belizatinib
(CAS: 1357920-84-3)

Belizatinib is inhibitor of both anaplastic lymphoma kinase (ALK) and tropomyosin-related kinases (TRK). Belizatinib can bind to and inhibit both ALK and TRK ki...

Reference Reading


1.Pyrazolylamine Derivatives Reveal the Conformational Switching between Type I and Type II Binding Modes of Anaplastic Lymphoma Kinase (ALK).
Tu CH1,2, Lin WH1, Peng YH1, Hsu T1, Wu JS1, Chang CY1, Lu CT1, Lyu PC2, Shih C1, Jiaang WT1, Wu SY1. J Med Chem. 2016 Apr 28;59(8):3906-19. doi: 10.1021/acs.jmedchem.6b00106. Epub 2016 Apr 12.
Most anaplastic lymphoma kinase (ALK) inhibitors adopt a type I binding mode, but only limited type II ALK structural studies are available. Herein, we present the structure of ALK in complex with N1-(3-4-[([5-(tert-butyl)-3-isoxazolyl]aminocarbonyl)amino]-3-methylphenyl-1H-5-pyrazolyl)-4-[(4-methylpiperazino)methyl]benzamide (5a), a novel ALK inhibitor adopting a type II binding mode. It revealed binding of 5a resulted in the conformational change and reposition of the activation loop, αC-helix, and juxtamembrane domain, which are all important domains for the autoinhibition mechanism and downstream signal pathway regulation of ALK. A structure-activity relationship study revealed that modifications to the structure of 5a led to significant differences in the ALK potency and altered the protein structure of ALK. To the best of our knowledge, this is the first structural biology study to directly observe how changes in the structure of a small molecule can regulate the switch between the type I and type II binding modes and induce dramatic conformational changes.
2.Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial.
Kim DW1, Mehra R2, Tan DS3, Felip E4, Chow LQ5, Camidge DR6, Vansteenkiste J7, Sharma S8, De Pas T9, Riely GJ10, Solomon BJ11, Wolf J12, Thomas M13, Schuler M14, Liu G15, Santoro A16, Sutradhar S17, Li S17, Szczudlo T17, Yovine A18, Shaw AT19. Lancet Oncol. 2016 Mar 10. pii: S1470-2045(15)00614-2. doi: 10.1016/S1470-2045(15)00614-2. [Epub ahead of print]
BACKGROUND: ALK-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often with progression in the brain. Ceritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood-brain barrier in vivo, and shows clinical responses in patients with crizotinib-resistant disease. We aimed to assess whole-body activity of ceritinib in both ALK inhibitor-pretreated and ALK inhibitor-naive patients with ALK-rearranged NSCLC.
3.Mouse models for ROS1-fusion-positive lung cancers and their application to the analysis of multikinase inhibitor efficiency.
Inoue M1, Toki H2, Matsui J2, Togashi Y3, Dobashi A4, Fukumura R5, Gondo Y5, Minowa O2, Tanaka N6, Mori S6, Takeuchi K3, Noda T7. Carcinogenesis. 2016 Mar 10. pii: bgw028. [Epub ahead of print]
ROS1-fusion genes, resulting from chromosomal rearrangement, have been reported in 1-2% of human non-small cell lung cancer cases. More than 10 distinctROS1-fusion genes, including break-point variants, have been identified to date. In this study, to investigate thein vivooncogenic activities of one of the most frequently detected fusions,CD74-ROS1, as well as anotherSDC4-ROS1fusion that has also been reported in several studies, we generated transgenic (TG) mouse strains that express either of the twoROS1-fusion genes specifically in lung alveolar type II cells. Mice in all TG lines developed tumorigenic nodules in the lung, and a few strains of both TG mouse lines demonstrated early-onset nodule development (multiple tumor lesions present in the lung at 2-4 weeks after birth); therefore, these two strains were selected for further investigation. Tumors developed progressively in the untreated TG mice of both lines, whereas those receiving oral administration of an ALK/MET/ROS1 inhibitor, crizotinib, and an ALK/ROS1 inhibitor, ASP3026, showed marked reduction in the tumor burden.
4.Metachronous primary uterine cancer surgically resected during Crizotinib treatment in a ALK-rearranged advanced lung adenocarcinoma.
Catino A1, Misino A1, Scattone A1, Caldarola L1, Petroni S1, Logroscino A1, Montagna ES1, Serio G1, Simone G1, Galetta D1. Transl Lung Cancer Res. 2016 Feb;5(1):145-9. doi: 10.3978/j.issn.2218-6751.2016.01.04.
Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3% to 7% of non-small-cell lung cancers (NSCLCs). Patients harboring ALK rearrangements show very favourable outcomes if treated with targeted agents, among which crizotinib is the first and best studied. Crizotinib, an oral small-molecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug. Nevertheless, the optimal therapy management with this new drug is still partially unknown, especially with regard to the safety of combined treatments. Recently, the integration of locoregional treatments has been proposed as a feasible multimodality strategy in selected patients with good clinical conditions and slow-growing or oligoprogressive disease. In this report, a case of advanced lung adenocarcinoma, progressed after first line chemotherapy and re-biopsied detecting ALK rearrangement, is described. During crizotinib treatment the primary lung tumor showed an excellent regression; meanwhile a major surgery for a metachronous uterine cancer was safely and successfully carried out.