Preclinical Pharmacology

Preclinical Pharmacology

  • Adejuwon Adeneye added an answer:
    Which triton (x 100 or wr1339) might be used to induce hyperlipidemia?

    In order to screen the hypolipidemic drugs, Triton induced hyperlipidemic animal model is being used. In most of the papers, Triton WR 1339 (tyloxapal) was used to induce hyperlipidemia. However, in some paper Triton X 100 was used. Which Triton is best or ideal to induce hyperlipidemia in rat model.

    Thanks in advance for replies.

    Adejuwon Adeneye · Lagos State University

    Triton WR-1339 reliably induces hyperlipidemia in rodents treated with it without fatalities unlike triton X-100 which kills animals as a result of its attendant hemolysis for which it is notoriously reputable. 

  • Joe Graymer added an answer:
    Who is carrying out preclinical research with Doxorubicin derivatives?

    In our research, we synthesized in a straightforward way a very potent fluorine derivative of Doxorubicin exhibiting nM IC50s in the two cell lines that we preliminarily tested. It could be especially interesting as a second-line treatment option (active in Dox-resistant strains) with possibly reduced cardiotoxicity.

    Unfortunately we lack the knowledge and/or research focus to carry out further studies.

    Does anybody know of a research group which is carrying out preclinical research on anthracycline derivatives?

    Answers are greatly appreciated

    Joe Graymer · NYAS

    Just before I started my residency in Clinical Oncology, the department I entered had been involved in the research of a Doxorubicin derivative, with some Iron added in a part of the molecule that I ignore, called 'Chelamycin', ('Quelamicina' in Spanish), in the aim of avoiding cardiac toxicity.

    The product in vials had a deep black color, and once clinical trials in Advanced Breast cancer started, they realized that the drug was much more toxic for cardiac muscle cells than the parent compound Doxorubicin, research was discontinued.

    I always had the feeling that this could have been expected, as Iron may act as a catalyst releasing Nascent Oxygen Species, that damage the cardiac muscular cells, but this is as speculative as the concept in the molecule was.

  • Robert Dettman added an answer:
    What is the most appropriate volume to be injected via IP in a mouse?
    I want to inject mice via IP route using 26-G needle for 2 weeks. Drug concentration to be used is e.g. 5mg/kg of body weight (0.025mg/1ml drug concentration). I intend to use 0.5 ml (for a mouse wieighing 25g). For example: A 24g mouse requires 0.48 ml ([24/25g] x [0.5ml]) and that IP injection requires at least 3.5 to 4 seconds. But, I'm worried the volume to be injected that is probably can cause stress or physical discomfort. Can I reduce the volume from 0.5ml to 0.4ml? Meaning (24/25g) x (0.4ml) = 0.38 ml. Is that ok?
    Robert Dettman · Stanley Manne Childrens Research Institute

    For larger volumes you can use Alzet pumps and these will carry out a continuous drug delivery, so that mice do not need to be injected multiple times. The pumps are placed subcutaneously and are well tolerated by adult mice.

  • Kulvinder Singh Saini added an answer:
    Where can we source New Chemical Entities (NCEs) against breast cancer, which failed in phase-1 or 2 clinical trials?

    Does anyone know, if global pharmaceutical/biotech companies/NIH, USA/USFDA, NGOs, etc. will be willing to give/sell us small amounts (mg quantity) of their small molecule compounds (NCEs), where possible toxicity issues hampered their clinical development as cancer therapeutics? We are interested in further exploring Toxicogenomics and mechanism-of-actions of these NCEs in a mouse model of breast cancer? Even NCEs which failed in clinical development against other cancers will be of great research interest to us.

    Kulvinder Singh Saini · King Abdulaziz University

    Please check this URL from AstraZeneca

  • Selva Chemist (Bio) added an answer:
    Does anyone know where I can obtain lyophilized herceptin for preclinical R&D?

    I am looking for lyophilized herceptin.  Would anyone (not affiliated with Genentech) be willing to provide this material?  Or do they know of another company that will sell it (or the generic version) to me?

    Selva Chemist (Bio) · GreyMatterResearch Foundation, India

    Dear Thad Wadas,

    Send your quires to us, www.gmrfoundation.com  , we can able to provide  lyophilized herceptin, if you need any other specification also inform us, For only R&D use, not for any human use.,

    Good Luck & Regards

    R.Selva.....

  • Bruce Koch added an answer:
    What are the best kinase inhibition profiling assays and microsome stability test systems for anti-tumor property screening?

    We test small molecule compounds for anti-tumor properties. We would like to test the kinase inhibition activity of our lead candidate. We don't know its biological target yet. No prior experience in these types of assays.

    Which is your favorite company/screening technology (in the United States) to test the kinase inhibition activity of your compound? Is a functional assay necessary or is a binding assay sufficient in this case?

    Also, which assay kit/company do you use for testing the microsome stability of your compound?

    Bruce Koch · Stanford University

    Our experience is that assaying a subset of the kinome is not very informative.  Inhibitors are often selective between closely related kinases, but then hit somewhere else in the kinome.  You might check out DiscoverX KinomeScan (formerly Ambit).

  • Neelima Jitendra Deuskar added an answer:
    Have you observed any differences in cell viability after treatment with chemotherapeutic agents with cells seeded on a flask vs. on a plate?

    I observed this phenomena with different cell lines and anticancer agents. To be specific for example, when A549 cells were treated with same concentration of taxol, less cells die if the cells were seeded in a 25cm2 or 75 cm2 flask compared to the cells seeded into 96 well plates (microscopic observation). Ratio of the seeded cell number to the surface area was the same, but the result did not change. Does anyone have an idea what might cause this?

    Neelima Jitendra Deuskar · University of Pune

     It is the quality of plasticware used that makes difference at times. Occasionally a particular lot even from a reputed brand does not give consistent results. It is necessary to rule out the margin/periphery/border effect seen in 96-well plates.

  • Does anyone know of a cell line that expresses R-D1 y R-D2L?
    Or maybe a well established protocol to induced SH-SY5Y to express them?
  • Majid Avijgan added an answer:
    Where can I test and confirm Anti-tuberculosis and Anti-HIV activity for Plant extract samples?

    Hi friends, I wish to do Antituberculosis and Anti HIV activity for Plant samples. Do you people know about any one doing out sourcing these experiments. I am ready to pay for this work. Or I will give authorship This  work is my own interest on natural drug discovery. 

    Majid Avijgan · Isfahan University of Medical Sciences

    I have several studies on the echinophora platyloba as an anti fungal herb. I have experience of what you are looking for. It is easy and simple, just invite from one of the pharmaceutic for co-operation. I have one co-worker in my paper as Dr Mohadese Mahboubi. Her email is as mahboubi1357@yahoo.com

  • Anju Wakade added an answer:
    How to extrapolate result from in vitro (ug/mL) to in vivo?
    I have obtained result from in vitro which 10 ug/mL. How to predict what value of doses we need to use in the mouse (mg/kg). Is there any specific calculation to extrapolate the data to mg/kg? or we need to test the doses beforehand?

    Your kind advice is greatly appreciated.
    hii
    I have a similar situation wherein the effective conc in vitro was 0.04% v/v and 0.08%v/v. i want to try it in mice (weighing 30-35mg) thru oral feeding. what conc should i use. My LD50 studies using oral route is 10ml/kg ie greater than 9257.50 mg/kg.
  • Pooja Shukla added an answer:
    How do you induce anemia in a guinea pig?
    I am evaluating hematological parameters in medicinal plants including anemia kindly tell me the methodology to induce anemia in guinea pigs, the reason to choose guinea pigs is the lower number of animals used and lower death rates.
  • Lawrence Broxmeyer, MD added an answer:
    Can anyone suggest a drug that can possibly be effective on an Alzheimer's rat model?
    I am having trouble finding a drug that crosses BBB and could possibly help to cure AD induced cognitive impairment in a rat model.
    Lawrence Broxmeyer, MD · NY Insitute of Med Research
    Run your study using standard antitubercular drugs to cure AD induced cognitive impairment in your rat model.
  • Can anybody help me to find an adapted center with which to perform preclinical studies of biosimilar drugs?
    It can be all around the world but an important matter is the cost. Please let me know about your experiences.
  • Martin Michael Dcona added an answer:
    How to work with carcinogenic and light sensitive drugs like Methotrexate?
    My colleague is working on Anti-Cancer Drug Delivery system mainly for Methotrexate. He needs guidelines on how to work with this light sensitive carcinogenic drug. Please suggest some documented guidelines.
    Martin Michael Dcona · Virginia Commonwealth University
    Could you be more specific? Are you talking about synthesis in which one of the reagents is methotrexate? or in vitro studies?
  • Vahid Fattahi added an answer:
    Has anybody worked on SKOV-3 cell lines induced xenograft mouse model using CD1 NUDE mice?
    Can anybody suggest about cell number/animal as well as time consumption to grow tumors up to palpable limit?
    Thanks a lot
  • Michael Linnebacher added an answer:
    Among CD1 Nude and Nu/Nu, which one is the best suitable immunocompromised Nude mouse model for MCF-7/ MDA MB-463?
    What all precautions i should take for the proper tumor growth using MCF-7 & MDA MB-463? How long does it take for the palpable tumor growth?
    Michael Linnebacher · University of Rostock
    Hi Milind,

    in principle, you have several issues to consider. First, the cell lines you are using (and also MF) are very old and frequently passaged. Consequently, the subclone of your lab may definitely behave different than the one used in other labs. And this independent from the mouse strain you are using. Thus, I agree with MF - you must check the growth characteristics of YOUR model.
    Second, of course the growth characteristics will additionally depend on the amount of cells you inject and on the injection side.
    Third, is the question you had in mind ;-): the best model for a very rapid tumor growth and best take rates is the NSG mouse followed by the NOD/SCID, the CD1 nude and than the nu/nu. However, in our hands the first two really make trouble sometimes because of their tendency towards spontaneous thymoma generation. Mostly at the side of the human tumor (maybe viruses???). And sorry, we did not work with CD1 nude on our own...
    But the nu/nu is a very nice model if the tumor or cell line you are working with engrafts in general. In more then 500 mice we had only once or twice something similar to thymoma ...
    Moreover, they are also cheaper (at least in Germany :-)) ...

    Michael Linnebacher
  • Ikhtifar Rafi added an answer:
    Preparation of experimental compound as well as dose calculation.
    I want to use a dose of 4mg/kg body weight of a compound (daily) through IP injection to 25 g mice. I intend to use max volume for IP injection which is 0.5 ml. vehicle in normal saline. How should the dose calculation be done? The compound is solid or powder.. Any suggestion?
    Ikhtifar Rafi · National University of Malaysia
    I would recommend to make it fresh if the stability is unknown. But shouldn't the research group know the stability of the compound?
  • Michael Niehaus added an answer:
    Informatics software for Pre-clinical Laboratory.
    Which software would you use for managing the informatics needs of your lab? In particular, a pre-clinical research lab.
    Michael Niehaus · Universität zu Lübeck
    I worked in a CRO and we used a customized version of Pristima
  • Milind Sagar added an answer:
    Does anybody have any experience with 786-O(RCC) induced xenograft nude mice models?
    Any suggestions about the optimum cell no. for inoculation as I had inoculated 786-O (5 *10 ^ 6 cells/animal, Subcutaneously in flank region) in CD1 nude mice. After one week I observed tumorous swellings up to 100 mm3 at the site of inoculation and then it disappeared after the 2nd week. What could be the reason?
    Milind Sagar · Dabur Research Foundation
    Thanks kunal & maqbool....yes now i am trying with multiple set of cells..

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