1. Membrane Transporter/Ion Channel
  2. Monocarboxylate Transporter
  3. AZD3965

AZD3965 

Cat. No.: HY-12750 Purity: 99.95%
Handling Instructions

AZD3965 is a selective MCT1 inhibitor with a Ki of 1.6 nM, showing 6-fold selectivity over MCT2.

For research use only. We do not sell to patients.

AZD3965 Chemical Structure

AZD3965 Chemical Structure

CAS No. : 1448671-31-5

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply Now  
10 mM * 1 mL in DMSO USD 163 In-stock
Estimated Time of Arrival: December 31
5 mg USD 144 In-stock
Estimated Time of Arrival: December 31
10 mg USD 180 In-stock
Estimated Time of Arrival: December 31
50 mg USD 540 In-stock
Estimated Time of Arrival: December 31
100 mg USD 900 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Based on 9 publication(s) in Google Scholar

Top Publications Citing Use of Products

    AZD3965 purchased from MCE. Usage Cited in: ACS Chem Biol. 2018 Jun 15;13(6):1480-1486.

    For analysis of dose responses, levels of thermostable SLC16A1 and SLCO1A2 are analyzed in lysates heated to 65 or 75°C, at 0, 5, 10, 20, 50, 100, and 1000 nM AZD3965.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    AZD3965 is a selective MCT1 inhibitor with a Ki of 1.6 nM, showing 6-fold selectivity over MCT2.

    IC50 & Target

    Ki: 1.6 nM (MCT1)[1]

    In Vitro

    AZD3965 is designed to selectively inhibit Monocarboxylate transporter-1 (MCT1) and will therefore be expected to influence the movement of lactate into and out of cells[1]. AZD3965 treatment causes a 3.7 fold increase in intracellular lactate in hypoxic COR-L103 and 3.7 fold and 3.9 fold increases in normoxic and hypoxic NCI-H1048 cells respectively. In all other cases a <1.9 fold increase is observed. These data are consistent with AZD3965 blocking lactate transport in cells where AZD3965 also reduces cell number and is consistent with AZD3965 acting via inhibition of MCT1. When MCT1 is overexpressed the EC50 of NCI-H1048 is increased from 0.14 nM to 10.5 nM in NCI-H1048 cells. This is consistent with AZD3965 acting via MCT1 inhibition[2].

    In Vivo

    COR-L103 tumor bearing mice are treated with 100 mg/kg AZD3965 or vehicle BIDfor 21 days and the tumor volume monitored. Pharmacokinetic analysis demonstrates that 100 mg/kg AZD3965 BID results in concentrations of free AZD3965 predicted to inhibit lactate transport. AZD3965 treatment significantly reduces the growth of COR-L103 tumors, although tumor regression is not seen, consistent with AZD3965 only targeting the hypoxic fraction of the tumor[2].

    Clinical Trial
    Molecular Weight

    515.51

    Formula

    C₂₁H₂₄F₃N₅O₅S

    CAS No.

    1448671-31-5

    SMILES

    O=C1N(C(C)C)C2=C(C(C(N3OC[[email protected]@](C)(O)C3)=O)=C(CC4=C(C)NN=C4C(F)(F)F)S2)C(N1C)=O

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 36 mg/mL (69.83 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.9398 mL 9.6991 mL 19.3983 mL
    5 mM 0.3880 mL 1.9398 mL 3.8797 mL
    10 mM 0.1940 mL 0.9699 mL 1.9398 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.08 mg/mL (4.03 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.08 mg/mL (4.03 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.08 mg/mL (4.03 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Kinase Assay
    [1]

    Cells are plated overnight and treated with 100 nM AZD3965 or vehicle for 24 hours. The cells are then washed, once in PBS and twice with lysis buffer (50 mM Mops, 100 mM KCl, 5 mM MgCl2, 1 mM EDTA, 0.1 mM DTT, 1 mM PMSF supplemented with 1× mini complete protease inhibitor cocktail tablets. The cells are harvested by scraping and centrifugation, and the pellet snap frozen without buffer in liquid nitrogen. Frozen aliquots of cells are thawed on ice and re-suspended in lysis buffer. Cells are lysed by 3 rounds of freezing in liquid nitrogen and thawing at 37°C for 2 minutes each. Lysates are subsequently centrifuged (13000 g, 10min, 4°C) until clear and then stored on ice. Enzyme activity in the cell lysates is determined using a micro-plate reader to measure either production or depletion of NADH/NADPH, through its absorbance at 340/10 nm, occurring as a result of direct or coupled enzyme reactions. The 96 well plates used for the assays are pre-heated to 37°C for 10 minutes prior to starting reactions, initiated by the addition of 5 μL cell lysate to 95 μL of reaction buffer (50 mM Mops pH 7.4, 100 mM KCl, 5 mM free magnesium). The standard reaction buffer is supplemented to assay the kinetics of the different enzymes. Absorbance values for controls are subtracted from absorbance of corresponding reactions. Graphpad prism 6 is used to plot V0 values against substrate concentration and determine Vmax and Km values. The Vmax is then normalised to the protein concentration in the cell lysate[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice[2]
    COR-L103 xenografts are grown by subcutaneous injection of 5×106 cells in 0.2 mL of 1:1 serum-free RPMI:Matrigel into the mid-dorsal flank of 8 to 14-week-old male NOD scid gamma mice. Mice are housed in individually vented caging systems in a 12-hour light/12-hour dark environment and maintained at uniform temperature and humidity. Tumor size is measured twice a week using calipers and the volume calculated as tumor length×tumor width2/2. 30 days after implantation, mice bearing tumors between 150 and 250mm3 are randomized into two groups of six and treated with 100 mg/kg BID AZD3965 in 0.5% hydroxypropyl methyl cellulose, 0.1% tween 80 or vehicle only by oral gavage for 21 days. Measurements are continued 3 times a week for the duration of drug treatment to assess tumor growth kinetics. At sacrifice tumors are collected to determine intra-tumor lactate concentration.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Purity: 99.95%

    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.
    • Molarity Calculator

    • Dilution Calculator

    The molarity calculator equation

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass   Concentration   Volume   Molecular Weight *
    = × ×

    The dilution calculator equation

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
    × = ×
    C1   V1   C2   V2

    Keywords:

    AZD3965AZD 3965AZD-3965Monocarboxylate TransporterInhibitorinhibitorinhibit

    Your Recently Viewed Products:

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product Name

     

    Salutation

    Applicant Name *

     

    Email address *

    Phone number *

     

    Organization name *

    Department *

     

    Requested quantity *

    Country or Region *

         

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    AZD3965
    Cat. No.:
    HY-12750
    Quantity:
    MCE Japan Authorized Agent: