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  1. #1
    oswaldosalcedo's Avatar
    oswaldosalcedo is offline Senior Member
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    igfbps inhibitors

    using igfbps inhibitors
    we would have more lr3 free,that way more lean mass.

  2. #2
    oswaldosalcedo's Avatar
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    J Med Chem. 2001 Nov 8;44(23):4001-10.

    Discovery of a series of nonpeptide small molecules that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins.

    Chen C, Zhu YF, Liu XJ, Lu ZX, Xie Q, Ling N.

    Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, California 92121, USA.


    going high boys,
    going high......................

  3. #3
    Pinnacle's Avatar
    Pinnacle is offline AR-Hall of Famer ~ Cocky motherF*cker!
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    Let's see the study and results Ossie.


    ~Pinnacle~

  4. #4
    supersteve Guest
    lr3 is already quite resistant to igfbp's isn't it?
    I thought this would be more relevant to igf-1.

  5. #5
    oswaldosalcedo's Avatar
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    Quote Originally Posted by Pinnacle
    Let's see the study and results Ossie.


    ~Pinnacle~
    take easy pinn, is just my hypothesis.
    science work by conjectures, hypothesis and tests and refutations.

    Differences in the association of insulin-like growth factor-I (IGF-I) and IGF-I variants with rat, sheep, pig, human and chicken plasma-binding proteins.

    Lord AP, Bastian SE, Read LC, Walton PE, Ballard FJ.

    Child Health Research Institute, North Adelaide, South Australia.

    "Associations between labelled insulin -like growth factors (IGFs) and IGF-binding proteins in plasma have been compared in the rat, sheep, human, pig and chicken. The IGFs tested were recombinant human IGF-I, the truncated variant, des(1-3)IGF-I, and LR3IGF-I, an extended form that had been engineered so as to minimize interactions with IGF-binding proteins. Marked species differences were demonstrated, notably that the IGF-I variants which exhibited extremely weak binding in rat plasma bound significantly in plasma from the other species. This result was shown both by size-exclusion chromatography of labelled IGFs added to plasma, in which the extent of variant IGF-I binding decreased in the order sheep > human > pig = chicken > rat, and by competition for labelled IGF-I binding in vitro, in which the order was pig = chicken > sheep > human > rat. Notwithstanding these differences, the two IGF-I variants showed only slight between-species binding differences when tested with purified rat, sheep and human IGF-binding protein-3. Ligand blotting experiments with plasma from the five species similarly showed a consistent pattern in that IGF-I binding was much greater than des(1-3)IGF-I binding, which in turn was greater than LR3IGF-I binding"

    less binding,more powerful.


    supersteve try to refute it.
    for example (but ignores knowledge........or worst, science at least !)
    and i answer to supersteve:

    but there is binding, any way and exist a form of LR3 that have less binding affinity than normal LR3 be media grade or receptor grade and is LR3 receptor grade biotinylated but,but..................it have binding affinity yet.............

    "quite" like stated supersteve is a big world yet........................

    QUITE:completely, entirely; truly, absolutely, extremely.

    opsss !!!
    like you see, strong world !

    it does not matter for me ............

    simply I look for the best thing !


    Endocrinology Vol. 142, No. 1 165-173
    Copyright © 2001 by The Endocrine Society


    Binding Protein-3-Selective Insulin-Like Growth Factor I Variants: Engineering, Biodistributions, and Clearance

    Yves Dubaquié, Deborah L. Mortensen, Anthony Intintoli, Deborah A. Hogue, Gerald Nakamura, Patricia Rancatore, Philip Lester, Michael D. Sadick, Ellen Filvaroff, Paul J. Fielder and Henry B. Lowman

    Departments of Protein Engineering (Y.D., G.N., H.B.L.), Pharmacokinetics and Metabolism (D.L.M., P.J.F.), Bioanalytical Technology (A.I., M.D.S.), Endocrinology (D.A.H., E.F.), and Recovery Sciences (P.R., P.L.), Genentech, Inc., South San Francisco, California 94080

    Insulin-like growth factor I (IGF-I) is a potent anabolic peptide that mediates most of its pleiotropic effects through association with the IGF type I receptor. Biological availability and plasma half-life of IGF-I are modulated by soluble binding proteins (IGFBPs), which sequester free IGF-I into high affinity complexes. Elevated levels of specific IGFBPs have been observed in several pathological conditions, resulting in inhibition of IGF-I activity. Administration of IGF-I variants that are unable to bind to the up-regulated IGFBP species could potentially counteract this effect. We engineered two IGFBP-selective variants that demonstrated 700- and 80,000-fold apparent reductions in affinity for IGFBP-1 while preserving low nanomolar affinity for IGFBP-3, the major carrier of IGF-I in plasma. Both variants displayed wild-type-like potency in cellular receptor kinase assays, stimulated human cartilage matrix synthesis, and retained their ability to associate with the acid-labile subunit in complex with IGFBP-3. Furthermore, pharmacokinetic parameters and tissue distribution of the IGF-I variants in rats differed from those of wild-type IGF-I as a function of their IGFBP affinities. These IGF-I variants may potentially be useful for treating disease conditions associated with up-regulated IGFBP-1 levels, such as chronic or acute renal and hepatic failure or uncontrolled diabetes. More generally, these results suggest that the complex biology of IGF-I may be clarified through in vivo studies of IGFBP-selective variants.

    and if we use igfbp inhibitors even better !
    oswaldo salcedo et all 2005.

    who knows ? 4-6 lbs more ?

    have to be a igfbp 3 inhibitor.



    Endocrinology. 2000 Nov;141(11):4171-9.
    Differential effects of insulin-like growth factor (IGF)-binding protein-3 and its proteolytic fragments on ligand binding, cell surface association, and IGF-I receptor signa ling.
    Devi GR, Yang DH, Rosenfeld RG, Oh Y.
    ---------------------------------------------------
    Endocrinology. 1993 Mar;132(3):1337-44.
    Characterization of the affinities of insulin-like growth factor (IGF)-binding proteins 1-4 for IGF-I, IGF-II, IGF-I/insulin hybrid, and IGF-I analogs.

    Oh Y, Muller HL, Lee DY, Fielder PJ, Rosenfeld RG.





    it takes brain man ! think deeper !

    refute with arguments,discuss with rational elements.

    ARGUMENT: a set of reasons given in support of something.


    .......................OBJECTIVE KNOWLEDGE.

    .................................Substantiate
    Last edited by oswaldosalcedo; 11-25-2005 at 10:53 AM.

  6. #6
    oswaldosalcedo's Avatar
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    a cycle with ILK 15,FS and LR3 receptor grade biotinylated can cost easy $ 10000-12000 monthly. aas apart.
    Last edited by oswaldosalcedo; 11-28-2005 at 06:21 PM.

  7. #7
    fishorcutbait is offline Junior Member
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    impractical and inconceivable for all but the richest, but for the richest... Stacked along with slin AAS and lr3 igf (would that be necessary?) thatd hit you up with some serious mass

  8. #8
    JohnnyB's Avatar
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    Quote Originally Posted by supersteve
    lr3 is already quite resistant to igfbp's isn't it?
    I thought this would be more relevant to igf-1.
    You're right

    JohnnyB

  9. #9
    Slic4788 is offline Associate Member
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    It would work, kinda like lowering SHBG for freeing up more test(proviron ), but hell its too expensive.

  10. #10
    JohnnyB's Avatar
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    Quote Originally Posted by Slic4788
    It would work, kinda like lowering SHBG for freeing up more test(proviron), but hell its too expensive.
    It's cheaper to buy LR3 IGf-1, since it binds poorly to IGF-1 BP

    JohnnyB

  11. #11
    oswaldosalcedo's Avatar
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    Quote Originally Posted by Slic4788
    It would work, kinda like lowering SHBG for freeing up more test(proviron), but hell its too expensive.
    that one !
    is the idea.

    but now it seems to me much better
    the myostatin propeptide and follistatin route.
    GDF8P and FS.

    Over-expression of myostatin propeptide in mice resulted in large increases (up to 200%) in skeletal muscle mass..................
    ...................................
    ...............................
    ....plus follistatin ????

    !!!!!
    Last edited by oswaldosalcedo; 11-29-2005 at 12:21 PM.

  12. #12
    oswaldosalcedo's Avatar
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    GDF8P and FS are products from big chem labs,not for retail or indiscriminate sale.
    all this is for informational purpose.

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