1. Protein Tyrosine Kinase/RTK
  2. ALK
    Insulin Receptor
    IGF-1R

LDK378 (Synonyms: Ceritinib)

Cat. No.: HY-15656 Purity: 99.75%
Data Sheet SDS Handling Instructions

LDK378 is a potent and more specific ALK inhibitor with IC50 of 0.2 nM.

For research use only. We do not sell to patients.
LDK378 Chemical Structure

LDK378 Chemical Structure

CAS No. : 1032900-25-6

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10 mM * 1 mL in DMSO $61 In-stock
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10 mg $70 In-stock
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100 mg $160 In-stock
200 mg $300 In-stock
500 mg $550 In-stock
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Customer Review

Other Forms of LDK378:

    LDK378 purchased from MCE. Usage Cited in: Mol Oncol. 2017 Aug;11(8):996-1006.

    Dose-response and time course comparison of ALK inhibition by Crizotinib or Ceritinib.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    LDK378 is a potent and more specific ALK inhibitor with IC50 of 0.2 nM.

    IC50 & Target

    IC50: 0.2 nM (ALK), 7 nM (InsR), 8 nM (IGF-1R), 23 nM (STK22D), 60 nM (FLT3), 260 nM (FGFR2)[1]

    In Vitro

    LDK378 (Ceritinib) also inhibits RET (IC50=400 nM), FGFR3 (IC50=430 nM), LCK (IC50=560 nM), JAK2 (IC50=610 nM), Aurora (IC50=660 nM), LYN (50=840 nM), EGFR (IC50=900 nM), and FGFR4 (IC50=950 nM)[1]. LDK378 retains high potency against the ALK enzymatic activity with an IC50 value of 200 pM and shows only strong inhibition against IGF-1R, InsR, and STK22D out of a panel of 46 kinases with a minimum selectivity of 70-fold. In Ba/F3 cells transfected with various kinases, LDK378 inhibits ALK activity with an IC50 value of 40.7 nM and had IC50 values of >100 nM against all other kinases tested. LDK378 shows potent antiproliferative activity with an IC50 value of 22.8 nM in Karpas 299 human non-Hodgkin’s Ki-positive large cell lymphoma carrying the NPM-ALK fusion gene and 26 nM in Ba/F3 cells transfected with the NPM-ALK fusion gene. LDK378 also shows good selectivity over wild-type Ba/F3 cells (IC50>2 μM) and Ba/F3 cells transfected with Tel-InsR gene (IC50=320 nM)[2].

    In Vivo

    The t1/2 of LDK378 in LDK378 mouse rat, dog, and monkey is 6.2 h, 9.1 h, 21 h, and 26 h,respectively[1]. LDK378 has an excellent pharmacokinetics profile in rodents and non-rodents with an oral bioavailability of >50%. LDK378 demonstrates dose-dependent tumor growth inhibition and achieved partial tumor regression in the Karpas 299 rat xenograft model with daily administration but is capable of achieving complete tumor regression in the H2228 NSCLC rat xenograft model, which carries the EML4-ALK fusion gene. In both models, LDK378 is well tolerated in animals. LDK378 is further assessed for its ADME profile and is found to have a relatively good metabolic stability in liver microsomes, modest CYP3A4 inhibition, some hERG inhibition with an IC50 value of 46 μM in hERG patch clamp experiments, but no evidence of QTc prolongation in both dog and monkey telemetry studies[2].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.7917 mL 8.9583 mL 17.9167 mL
    5 mM 0.3583 mL 1.7917 mL 3.5833 mL
    10 mM 0.1792 mL 0.8958 mL 1.7917 mL
    Please refer to the solubility information to select the appropriate solvent.
    Animal Administration
    [1]

    LDK378 (HCl salt) is formulated as a solution in 75% PEG300/25% D5W[1].
    LDK378 (phosphate salt) as an intravenous solution in 30% propylene glycol/5% solutol buffer and an oral suspension in suspension in 0.5% (w/v) aqueous methylcellulose/0.5% Tween 80[1].
    LDK378 (free base) as an intravenous solution in 30% propylene glycol/5% solutol and an oral suspension in 0.5% (w/v) methylcellulose[1].

    In vivo PK studies are conducted in mice, rats, dogs, and cynomolgus monkeys. LDK378 (HCl salt) is administered to male Balb/c mice intravenously via tail vein at 5 mg/kg (n=3) and orally via gavage at 20 mg/kg (n=3). By use of the same formulation, LDK378 (HCl salt) is dosed to Sprague-Dawley rats intravenously via the tail vein at 3 mg/kg (n=3) and orally via gavage at 10 mg/kg (n=3). Blood samples are collected serially at scheduled times over 24 h after dosing. Male beagle dogs receive a single intravenous (n=2) or oral (n=3) dose of LDK378 (phosphate salt) as an intravenous solution at 5 mg/kg and an oral suspension at 20 mg/kg, respectively. Male cynomologus monkeys receive single intravenous (n=2) or oral (n=3) dose of LDK378 (free base) as an intravenous solution at 5 mg/kg and an oral suspension at 60 mg/kg, respectively. Blood samples for plasma are collected at prescheduled times over 144 h after dosing[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    558.14

    Formula

    C₂₈H₃₆ClN₅O₃S

    CAS No.

    1032900-25-6

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: 5.6 mg/mL (Need ultrasonic)

    LDK378 (Ceritinib) is dissolved in 0.5% methylcellulose, 0.5% Tween 80 with sterile water[3].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

    Purity: 99.75%

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    LDK378
    Cat. No.:
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