LDK378Potent ALK inhibitor CAS# 1032900-25-6 |
- AP26113
Catalog No.:BCC1069
CAS No.:1197958-12-5
- LDK378 dihydrochloride
Catalog No.:BCC1694
CAS No.:1380575-43-8
- ALK inhibitor 2
Catalog No.:BCC1340
CAS No.:761438-38-4
- TAE684 (NVP-TAE684)
Catalog No.:BCC3660
CAS No.:761439-42-3
- (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. | 1032900-25-6 | SDF | Download SDF |
PubChem ID | 57379345 | Appearance | Powder |
Formula | C28H36ClN5O3S | M.Wt | 558.14 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | Ceritinib | ||
Solubility | DMSO : 5.6 mg/mL (10.03 mM; Need ultrasonic) Ethanol : ≥ 3.33 mg/mL (5.97 mM) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | 5-chloro-2-N-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyphenyl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine | ||
SMILES | CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl | ||
Standard InChIKey | VERWOWGGCGHDQE-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C28H36ClN5O3S/c1-17(2)37-25-15-21(20-10-12-30-13-11-20)19(5)14-24(25)33-28-31-16-22(29)27(34-28)32-23-8-6-7-9-26(23)38(35,36)18(3)4/h6-9,14-18,20,30H,10-13H2,1-5H3,(H2,31,32,33,34) | ||
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 | LDK378 is potent inhibitor of ALK with IC50 of 0.2 nM, shows 40- and 35-fold selectivity against IGF-1R and InsR, respectively. | |||||
Targets | ALK | |||||
IC50 | 0.2 nM |
LDK378 Dilution Calculator
LDK378 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 1.7917 mL | 8.9583 mL | 17.9167 mL | 35.8333 mL | 44.7916 mL |
5 mM | 0.3583 mL | 1.7917 mL | 3.5833 mL | 7.1667 mL | 8.9583 mL |
10 mM | 0.1792 mL | 0.8958 mL | 1.7917 mL | 3.5833 mL | 4.4792 mL |
50 mM | 0.0358 mL | 0.1792 mL | 0.3583 mL | 0.7167 mL | 0.8958 mL |
100 mM | 0.0179 mL | 0.0896 mL | 0.1792 mL | 0.3583 mL | 0.4479 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
LDK378 is a highly potent inhibitor of anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase belonging to the superfamily of insulin receptor, with half maximal inhibitory concentration IC50 of 200 pM. LDK378 also exhibits modest to high inhibition against a panel of other kinases, in which only three kinases with IC50 below 100 nM includes IGF-1R (8 nM), InsR (7 nM) and STK22D (23 nM). In previous studies, LDK378 has been found to inhibit the proliferation of Ba/F3 cells transfected with the NPM-ALK fusion gene and Karpas 299 human non-Hodgkin’s Ki-positivr large cell lymphoma harboring the NPM-ALK fusion gene with IC50 of 22.8 nM and 26 nM.
References:
[1]Chen J, Jiang C, Wang S. LDK378: a promising anaplastic lymphoma kinase (ALK) inhibitor. J Med Chem. 2013 Jul 25;56(14):5673-4. doi: 10.1021/jm401005u. Epub 2013 Jul 9.
[2]Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26.
- GSK1292263
Catalog No.:BCC3786
CAS No.:1032823-75-8
- PTIQ
Catalog No.:BCC7953
CAS No.:1032822-42-6
- GDC-0980 (RG7422)
Catalog No.:BCC4992
CAS No.:1032754-93-0
- GNE-477
Catalog No.:BCC8049
CAS No.:1032754-81-6
- BAY 80-6946 (Copanlisib)
Catalog No.:BCC4986
CAS No.:1032568-63-0
- L-655,240
Catalog No.:BCC7156
CAS No.:103253-15-2
- MK-2206 dihydrochloride
Catalog No.:BCC1274
CAS No.:1032350-13-2
- D-Arabinose
Catalog No.:BCN3791
CAS No.:10323-20-3
- A939572
Catalog No.:BCC5305
CAS No.:1032229-33-6
- Fmoc-Cys(Trt)-OH
Catalog No.:BCC3479
CAS No.:103213-32-7
- Fmoc-Tyr(3,5-I2)-OH
Catalog No.:BCC3264
CAS No.:103213-31-6
- Pranlukast
Catalog No.:BCC4827
CAS No.:103177-37-3
- Taltirelin
Catalog No.:BCC5271
CAS No.:103300-74-9
- Pre-schisanartanin B
Catalog No.:BCN5846
CAS No.:1033288-92-4
- 3-Oxo-4-aza-5-alpha-androstane-17β-carboxylic acid
Catalog No.:BCC8641
CAS No.:103335-55-3
- L-364,373
Catalog No.:BCC7445
CAS No.:103342-82-1
- 1-Methyl-L-4,5-dihydroorotic acid
Catalog No.:BCC8472
CAS No.:103365-69-1
- GNE-493
Catalog No.:BCC8048
CAS No.:1033735-94-2
- Itol A
Catalog No.:BCN5847
CAS No.:1033747-78-2
- GNF-5837
Catalog No.:BCC3668
CAS No.:1033769-28-6
- Salidroside
Catalog No.:BCN5966
CAS No.:10338-51-9
- Telotristat
Catalog No.:BCC5128
CAS No.:1033805-28-5
- HPGDS inhibitor 1
Catalog No.:BCC4065
CAS No.:1033836-12-2
- 1-O-Methylnataloe-emodin
Catalog No.:BCN7036
CAS No.:103392-51-4
Effect of ceritinib (LDK378) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo.[Pubmed:26556876]
Oncotarget. 2015 Dec 29;6(42):44643-59.
Multidrug resistance (MDR) is the leading cause of treatment failure in cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2, play a key role in mediating MDR by pumping anticancer drugs out from cancer cells. Ceritinib (LDK378) is a second-generation tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) currently in phase III clinical trial for the treatment of non-small cell lung cancer. Here, we found that ceritinib remarkably enhanced the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 over-expressing cancer cells in vitro and in vivo. Ceritinib significantly increased the intracellular accumulation of chemotherapeutic agents such as doxorubicin (DOX) by inhibiting ABCB1 or ABCG2-mediated drug efflux in the transporters-overexpressing cells. Mechanistically, ceritinib is likely a competitive inhibitor of ABCB1 and ABCG2 because it competed with [(125)I]-iodoarylazidoprazosin for photo affinity labeling of the transporters. On the other hand, at the transporters-inhibiting concentrations, ceritinib did not alter the expression level of ABCB1 and ABCG2, and phosphorylation status of AKT and ERK1/2. Thus the findings advocate further clinical investigation of combination chemotherapy of ceritinib and other conventional chemotherapeutic drugs in chemo-refractory cancer patients.
Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors.[Pubmed:26020125]
J Thorac Oncol. 2015 Jul;10(7):1058-66.
INTRODUCTION: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK inhibitors, but resistance develops. This study assessed the maximum-tolerated dose, safety, pharmacokinetics (PK), and antitumor activity of ceritinib, a novel ALK inhibitor (ALKi), in Japanese patients with ALK-rearranged malignancies. METHODS: This phase I, multicenter, open-label study (NCT01634763) enrolled adult patients with ALK-rearranged (by fluorescence in situ hybridization and/or immunohistochemistry) locally advanced/metastatic malignancy that had progressed despite standard therapy. The study comprised two parts: dose escalation and dose expansion. Ceritinib (single-dose) was administered orally in the 3-day PK run-in period, then once daily, in 21-day cycles. Adaptive dose escalations were guided by a Bayesian model. RESULTS: Twenty patients (80% with ALKi treatment history [ALKi-pretreated]; 19 NSCLC; one inflammatory myofibroblastic tumor) received ceritinib 300 to 750 mg (19 during dose escalation, one in dose expansion). Two dose-limiting toxicities occurred: grade 3 lipase increase (600 mg); grade 3 drug-induced liver injury (750 mg). The most common adverse events were gastrointestinal (nausea: 95%; diarrhea, vomiting: 75%). Ceritinib PK profile was dose proportional across 300 to 750 mg dosages; steady state was reached by day 15. Overall response rate was 55% (11 of 20 patients). Among patients with NSCLC, partial response was observed in two of four ALKi-naive patients, five of nine crizotinib-pretreated patients, two of four alectinib-pretreated patients, and one of two crizotinib and alectinib/ASP3026 pretreated patients. The ASP3026-pretreated inflammatory myofibroblastic tumor patient achieved partial response. CONCLUSIONS: Ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing.
Ceritinib (LDK378): a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer.[Pubmed:25458559]
Clin Lung Cancer. 2015 Mar;16(2):86-91.
The success in identifying the chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) as an oncogenic driver has thoroughly changed the treatment of non-small-cell lung cancer. In the past decade, targeted drugs have emerged as an efficient personalized strategy for ALK-rearranged non-small-cell lung cancer. The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design. In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.