CH5424802ALK inhibitor,potent and ATP-competitive CAS# 1256580-46-7 |
- ASP3026
Catalog No.:BCC1372
CAS No.:1097917-15-1
- AP26113
Catalog No.:BCC1069
CAS No.:1197958-12-5
- ALK inhibitor 1
Catalog No.:BCC1339
CAS No.:761436-81-1
- ALK inhibitor 2
Catalog No.:BCC1340
CAS No.:761438-38-4
- (R)-Crizotinib
Catalog No.:BCC1284
CAS No.:877399-52-5
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 1256580-46-7 | SDF | Download SDF |
PubChem ID | 49806720 | Appearance | Powder |
Formula | C30H34N4O2 | M.Wt | 482.62 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | Alectinib; AF802 | ||
Solubility | DMSO : 6.2 mg/mL (12.85 mM; Need warming) H2O : < 0.1 mg/mL (insoluble) | ||
Chemical Name | 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-ylpiperidin-1-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile | ||
SMILES | CCC1=C(C=C2C(=C1)C(=O)C3=C(C2(C)C)NC4=C3C=CC(=C4)C#N)N5CCC(CC5)N6CCOCC6 | ||
Standard InChIKey | KDGFLJKFZUIJMX-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C30H34N4O2/c1-4-20-16-23-24(17-26(20)34-9-7-21(8-10-34)33-11-13-36-14-12-33)30(2,3)29-27(28(23)35)22-6-5-19(18-31)15-25(22)32-29/h5-6,15-17,21,32H,4,7-14H2,1-3H3 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Alectinib (CH5424802) is a potent inhibitor of ALK with an IC50 value of 1.9 nM. | ||||||
Targets | ALK (F1174L) | ALK | ALK (R1275Q) | INSR | KDR | ||
IC50 | 1 nM | 1.9 nM | 3.5 nM | 550 nM | 1.4 μM |
CH5424802 Dilution Calculator
CH5424802 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.072 mL | 10.3601 mL | 20.7202 mL | 41.4405 mL | 51.8006 mL |
5 mM | 0.4144 mL | 2.072 mL | 4.144 mL | 8.2881 mL | 10.3601 mL |
10 mM | 0.2072 mL | 1.036 mL | 2.072 mL | 4.144 mL | 5.1801 mL |
50 mM | 0.0414 mL | 0.2072 mL | 0.4144 mL | 0.8288 mL | 1.036 mL |
100 mM | 0.0207 mL | 0.1036 mL | 0.2072 mL | 0.4144 mL | 0.518 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
CH5424802 is a potent and selective ALK inhibitor.
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that is constitutively activated in certain cancers. .
In vitro: In cell free assays the IC50 of CH5424802 for enzyme activity of ALK was 1.9 nM; the dissociation constant (KD) value for ALK in an ATP-competitive manner was 2.4 nM. The inhibitory activity for two hot spot-activating mutations (F1174L and R1275Q) in neuroblastoma was comparable to that for wildtype ALK [1].
In vivo: In the NCI-H2228 model, oral administration of CH5424802 resulted in dose-dependent tumor growth inhibition (ED50 = 0.46 mg/kg) and tumor regression. Moreover, treatment of 20 mg/kg CH5424802 showed rapid tumor regression and tumor regrowth did not occur throughout the 4-week drug-free period [2].
Clinical trial: No clinical data are available currently.
Reference:
[1] Sakamoto H, Tsukaguchi T, Hiroshima S, Kodama T, Kobayashi T, Fukami TA, Oikawa N, Tsukuda T, Ishii N, Aoki Y. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.
- Ledipasvir
Catalog No.:BCC1696
CAS No.:1256388-51-8
- RuBi-Nicotine
Catalog No.:BCC7793
CAS No.:1256362-30-7
- AI-10-49
Catalog No.:BCC3973
CAS No.:1256094-72-0
- TRX818
Catalog No.:BCC6458
CAS No.:1256037-58-7
- [Leu31,Pro34]-Neuropeptide Y (porcine)
Catalog No.:BCC5716
CAS No.:125580-28-1
- Rotigotine hydrochloride
Catalog No.:BCC1908
CAS No.:125572-93-2
- MnTMPyP Pentachloride
Catalog No.:BCC6532
CAS No.:125565-45-9
- UNC0638
Catalog No.:BCC1135
CAS No.:1255580-76-7
- PF-4708671
Catalog No.:BCC5031
CAS No.:1255517-76-0
- LY 233053
Catalog No.:BCC5771
CAS No.:125546-04-5
- 3',5,5',7-Tetrahydroxy-4',6-dimethoxyflavone
Catalog No.:BCN6136
CAS No.:125537-92-0
- Dracorhodin perchlorate
Catalog No.:BCN2628
CAS No.:125536-25-6
- Blinin
Catalog No.:BCN8455
CAS No.:125675-09-4
- 3''-O-acetyl-platyconic acid A
Catalog No.:BCN3319
CAS No.:1256935-28-0
- 2''-O-acetyl-platyconic acid A
Catalog No.:BCN3318
CAS No.:1256935-30-4
- CDK4 inhibitor
Catalog No.:BCC4242
CAS No.:1256963-02-6
- Lavendustin B
Catalog No.:BCN1809
CAS No.:125697-91-8
- Lavendustin A
Catalog No.:BCN1808
CAS No.:125697-92-9
- (-)-Epicatechin gallate
Catalog No.:BCN6327
CAS No.:1257-08-5
- TBTU
Catalog No.:BCC2823
CAS No.:125700-67-6
- TDBTU
Catalog No.:BCC2825
CAS No.:125700-69-8
- TPTU
Catalog No.:BCC2827
CAS No.:125700-71-2
- ABT-199
Catalog No.:BCC3614
CAS No.:1257044-40-8
- TC-SP 14
Catalog No.:BCC7926
CAS No.:1257093-40-5
Alectinib (CH5424802) antagonizes ABCB1- and ABCG2-mediated multidrug resistance in vitro, in vivo and ex vivo.[Pubmed:28303028]
Exp Mol Med. 2017 Mar 17;49(3):e303.
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo. Mechanistically, alectinib increased the intracellular accumulation of ABCB1/ABCG2 substrates such as doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, alectinib stimulated ATPase activity and competed with substrates of ABCB1 or ABCG2 and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling bound to ABCB1 or ABCG2 but neither altered the expression and localization of ABCB1 or ABCG2 nor the phosphorylation levels of AKT and ERK. Alectinib also enhanced the cytotoxicity of DOX and the intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. These findings suggest that alectinib combined with traditional chemotherapy may be beneficial to patients with ABCB1- or ABCG2-mediated MDR.
Interstitial lung disease induced by alectinib (CH5424802/RO5424802).[Pubmed:25398579]
Jpn J Clin Oncol. 2015 Feb;45(2):221-4.
A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile.
Next-generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib.[Pubmed:24736079]
J Thorac Oncol. 2014 Apr;9(4):549-53.
Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment. Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib. In a second case, we identified a secondary acquired ALK G1202R, which also confers resistance to alectinib (CH5424802/RO5424802), a second-generation ALK inhibitor that can inhibit ALK gatekeeper L1196M mutation in vitro. ALK G1202R is located at the solvent front of the ALK kinase domain and exhibits a high level of resistance to all other ALK inhibitors currently in clinical development in vitro. Comprehensive genomic profiling of resistant tumor is increasingly important in tailoring treatment decisions after disease progression on crizotinib in ALK+ NSCLC given the promise of second-generation ALK inhibitors and other therapeutic strategies.