44 replies to this topic

[telight]

My isozazole-9 (ISX-9) from TeamTLR came yesterday to my apartment. Unfortunately, I am current away and will be back next week. I can only assume this means that some of you will also begin receiving your ISX-9 shipments.

 

The main thread is here. Basically, this drug has potential for increasing synaptogensis which would help with the integration of freshly created neurons into existing neural networks. An idea would be to increase neurogenesis via a drug like NSI-189, and then quickly integrate the new neurons using ISX-9.

 

Using this study and the HED equivalent for mice we find that 20/12.3*75=122mg would be an a human equivalent oral dose. As usual I will start with 1/10 of this dose (~10mg) sublingually and see how I fare. Expect an update from me in about a week in half.

 

I am sure someone already has access to the compound and has begun experimenting. Please tell us about your progress!

[telight]

I took 15mg sublingually about 4 hours ago. I experienced no positive or negative effects. This is still an order of magnitude less than the equivalent human.

 

The drug is supposed to have a 25 min half life in the brain. But this says nothing about the actual half life of the drug since a good portion of it is probably bound to plasma proteins and as the drug is "used up" in the brain more drug unbind from plasma proteins to preserve equilibrium of bound/unbound drug  in the blood; thus extending the effect of the drug.

 

I would love to see some pharmacokinetics for this compound.

 

 

Just took another 35mg sublingually. Good thing about this compound is that it is completely tasteless!

Edited by telight, 25 July 2014 - 11:11 PM.

[Amorphous]

Please keep us updated. Are you taking any other nootropic?

[telight]

I noticed vivid dreams from my last 35mg dose. There was maybe some positive effects on mental clarity but they were not large enough for me to say that the effect was not placebo with certainty.

 

My last dose of fasoracetam was about 3 days ago now. I am still feeling its effects on caffeine tolerance and orgasm. I also injected 800ug of semax the morning of my trial. I will start with 60mg sublingually this morning and see what happens.

[telight]

I am still trying to understand the drugs effects. But I can say that I definitely felt something at the 60mg dose and that I experienced no side effects even at larger 100mg dose sublingually and a 130mg dose orally.

Edited by telight, 27 July 2014 - 09:31 PM.

[Amorphous]

Telight, hopefully you are still around. I'll have my rat to try it in a few day. Hopefully, it will not have the same effect as CPH4, and my rat will not vanish into thin air

[Milkyway]

I would like to be kept informed of peoples experiences with this.

[Amorphous]

Just got confirmation about my order of ISX9. I think I will be receiving tomorrow or next monday. I will start experimenting it as soon as receiving it. 

[megatron]

Just got confirmation about my order of ISX9. I think I will be receiving tomorrow or next monday. I will start experimenting it as soon as receiving it. 

 

From teamtlr.com? It doesn't seen like they have it stocked.

[golden1]

 

Just got confirmation about my order of ISX9. I think I will be receiving tomorrow or next monday. I will start experimenting it as soon as receiving it. 

 

From teamtlr.com? It doesn't seen like they have it stocked.

 

I recently got 500mg from them.. their website must be incorrect I guess since it said the same when I ordered. ofc, they are sketch, so I'm not 100% sure on anything.

Edited by golden1, 02 August 2014 - 11:34 PM.

[medicineman]

they are no more sketch than any other rc business. they supply COAs as needed, and are helpful in regards to any inquiry. I am in no way affiliated with them, but have dealt with them and I experienced no trouble. if you have any issues, just contact them.

[Amorphous]

Just got confirmation about my order of ISX9. I think I will be receiving tomorrow or next monday. I will start experimenting it as soon as receiving it.

From teamtlr.com? It doesn't seen like they have it stocked.

Yes, it is from teamtlr. I ordered it as a pre-order. Thursday I got a postal confirmation. I don't think I'll get it today. It is still in NY. Hopefully, I'll get it on Monday.

[golden1]

they are no more sketch than any other rc business. they supply COAs as needed, and are helpful in regards to any inquiry. I am in no way affiliated with them, but have dealt with them and I experienced no trouble. if you have any issues, just contact them.

 

read their about page and the posts they made here... sketch.. hard to deny.

[Amorphous]

Any feedback from anyone?

[sk_scientific]

ISX 9 induces expression of NeuroD1?

 

NeuroD1 and TrkB possibly involved in diabetes and cancer.

 

THOUGHTS?

 

http://www.nature.co...sis201324a.html

[Amorphous]

Interesting, it seems like shorter term exposure may minimize its potential adverse effects. Anyone knows how long it takes the mouse to be on it to begin to improve its memory performance?.
I already took a 60mg dose last night. It didn't seem to have any effect at all. I took another dose this morning and it didn't seem like to do anything. However, I was under a lot of stress due to a sudden change of deadline of a project last night, and I only had a few hours of sleep today. Also I just ended my NSI cycle just last week. About 2 months continued use of NSI just made me feel so tired. I think 1 month cycling makes more sense.

Edited by Amorphous, 06 August 2014 - 01:32 AM.

[sk_scientific]

"Seems like" according to what data?

[Metagene]

Yeah let's not lose our heads here.

http://www.ncbi.nlm....les/PMC3251102/

[sk_scientific]

From the other thread directing to the current thread:

 

 

I have received ISX-9 and will not begin dosing until the middle of next week.  In the interim, I am researching what little information there is on the compound and its peripheral actions, such as the induction of NeuroD1 expression.  I'm not disposed to the notion that enhanced NeuroD1 expression in the pacreas is necessarily desireable.  Be informed that ISX-9 purportedly manipulates an allele in your DNA.

 

We haven't established what a safe amount, and perhaps more especially, what a safe duration of doseage is for this substance.  Until I know more, I am inclined to tread very lightly.  I will appreciate any user experiences in the feedback thread.  It would be very beneficial for us to have an individual who is not needle adverse to monitor their blood sugar.  I'm extremely needle adverse so in this go-round I'm going to have to hand that torch to another (unless of course we do find that this substance does dramatically effect insulin levels and in such case it would become a necessity that anyone ingesting it monitor their blood sugar levels).

 

Please update in the  ISX-9 feedback thread.

 

[Metagene]

Overexpression of BETA2/NeuroD induces neurite outgrowth in F11 neuroblastoma cells.

 

BETA2/NeuroD, a basic helix-loop-helix (bHLH) transcription factor, has been shown to play important roles in the development of the nervous system and the maintenance and formation of pancreatic and enteroendocrine cells. The gain of function of BETA2/NeuroD in neurogenesis has been shown in Xenopus embryos. In this study, we investigated the neurogenic potential of BETA2/NeuroD using neuroblastoma cell line, F11, which could be induced to differentiate into neurons in the presence of cAMP. To induce or block the expression of BETA2/NeuroD, expression vectors for the full-length and a C-terminal deletion mutant of BETA2 were constructed and their transactivation potential was verified using reporter genes containing the insulin promoter sequences. Overexpression of BETA2 with full-length construct induced neurite outgrowth in F11 cells in the absence of cAMP. In contrast, the C-terminal deletion mutant, BETA2(1--233), which has dominant negative activity, inhibited neurite outgrowth induced by cAMP in F11 cells. These results indicate that BETA2/NeuroD plays an important role in terminal differentiation of neuroblastoma cells. They also imply that BETA2/NeuroD or related bHLH factors plays an essential role for differentiation of F11 neuroblastoma cells.

 

 

 

 

 

The basic helix–loop–helix protein BETA2 interacts with p300 to coordinate differentiation of secretin-expressing enteroendocrinecells

 

The major epithelial cell types lining the intestine comprise a perpetually self-renewing population of cells that differentiate continuously from a stem cell in the intestinal crypts. Secretin-producing enteroendocrine cells represent a nondividing subpopulation of intestinal epithelial cells, suggesting that expression of the hormone is coordinated with cell cycle arrest during the differentiation of this cell lineage. Here we report that the basic helix–loop–helix protein BETA2 associates functionally with the coactivator, p300 to activate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor p21. Overexpression of BETA2 in cell lines induces both cell cycle arrest and apoptosis suggesting that BETA2 may regulate proliferation of secretin cells. Consistent with this role, we observed both reentry of normally quiescent cells into the cell cycle and disrupted cell number regulation in the small intestine of BETA2 null mice. Thus, BETA2 may function to coordinate transcriptional activation of the secretin gene, cell cycle arrest, and cell number regulation, providing one of the first examples of a transcription factor that controls terminal differentiation of cells in the intestinal epithelium.

 

 

^

Overexpression of BETA2 induces apoptosis in transfected cells.  

 

http://www.ncbi.nlm....pubmed/11279266

 

http://www.ncbi.nlm....cles/PMC316627/

 

 

Edited by Metagene, 06 August 2014 - 03:37 PM.

[sk_scientific]

Mind elaborating your understanding of this?  This is a little outside of my expertise.

[Metagene]

Mind elaborating your understanding of this?  This is a little outside of my expertise.

 

I was going to ask you the same thing    From what I can understand  Isx activates NeuroD1 thru the ERK1/2 signing  pathway not TrkB 

 

 

 

 NeuroD1 was implicated in the tumorigenesis of neuroblastoma.³⁶ Our data reveal a novel function for NeuroD1 in the induction and coordination of signal transduction pathways that regulate survival and migration of non-neural/neuroendocrine cancers. We now demonstrate that NeuroD1 promotes survival and migration in neuroendocrine lung and other carcinomas at least in part through TrkB.

 

 

 

The neuronal differentiation factor NeuroD1 downregulates the neuronal repellent factor Slit2 expression and promotes cell motility and tumor formation of neuroblastoma.

 

The basic helix-loop-helix transcription factor NeuroD1 has been implicated in the neurogenesis and early differentiation of pancreatic endocrine cells. However, its function in relation to cancer has been poorly examined. In this study, we found that NeuroD1 is involved in the tumorigenesis of neuroblastoma. NeuroD1 was strongly expressed in a hyperplastic region comprising neuroblasts in the celiac sympathetic ganglion of 2-week-old MYCN transgenic (Tg) mice and was consistently expressed in the subsequently generated neuroblastoma tissue. NeuroD1 knockdown by short hairpin RNA (shRNA) resulted in motility inhibition of the human neuroblastoma cell lines, and this effect was reversed by shRNA-resistant NeuroD1. The motility inhibition by NeuroD1 knockdown was associated with induction of Slit2 expression, and knockdown of Slit2 could restore cell motility. Consistent with this finding, shRNA-resistant NeuroD1 suppressed Slit2 expression. NeuroD1 directly bound to the first and second E-box of the Slit2 promoter region. Moreover, we found that the growth of tumor spheres, established from neuroblastoma cell lines in MYCN Tg mice, was suppressed by NeuroD1 suppression. The functions identified for NeuroD1 in cell motility and tumor sphere growth may suggest a link between NeuroD1 and the tumorigenesis of neuroblastoma. Indeed, tumor formation of tumor sphere-derived cells was significantly suppressed by NeuroD1 knockdown. These data are relevant to the clinical features of human neuroblastoma: high NeuroD1 expression was closely associated with poor prognosis. Our findings establish the critical role of the neuronal differentiation factor NeuroD1 in neuroblastoma as well as its functional relationship with the neuronal repellent factor Slit2.

 

 

 

^

This is in TH-MYCN transgenic mice like the other study so I'm not worry yet.  http://www.ncbi.nlm....pubmed/22777578

 

Reading comprehension can only take me so far but I'll see what else I can find.

[sk_scientific]

 

 

NeuroD1 knockdown by short hairpin RNA (shRNA) resulted in motility inhibition of the human neuroblastoma cell lines, and this effect was reversed by shRNA-resistant NeuroD1. The motility inhibition by NeuroD1 knockdown was associated with induction of Slit2 expression, and knockdown of Slit2 could restore cell motility. 

 

This looks to me to imply that NeuroD1 expression from ISX-9 puts you at a greater risk of cancer should an emerging neuroblast have the propensity for malignancy.

 

This isn't like oh we have more BDNF available, growth means cancer.  More like, oh we have a potential cancer cell and this will increase its ability to move and proliferate.

 

Now, I could be wrong but this doesn't bode well.  Let's do some more digging around on this.

 

Also take note of the word "human" in the above caption.

Edited by sk_scientific, 06 August 2014 - 05:48 PM.

[sk_scientific]

Here is another study, but that shows isx-9 can cross the BBB.  I need to look at it more closely this weekend when I'm not at work.

 

http://www.fasebj.or...201426.full.pdf

 

 

MS analysis revealed that

intraperitoneal Isx-9 passes the BBB into the brain (Fig.

1B) and even into the hippocampus (e.g., 1332 ng

Isx-9/g hippocampal tissue). Isx-9 had a brain tissue

half-life of 25 min (Fig. 1B). Isx-9 was well tolerated,

as there was no difference in weight or weight gain vs.

Veh after either 7 d (Fig. 1C) or 12 d (Supplemental

Fig. S1A) 

Edited by sk_scientific, 06 August 2014 - 08:07 PM.

[drg]

Still waiting on a more detailed account of isx-9 from anyone who has tried it. 

[megatron]

Updates?

[megatron]

Ah, I finally received my ISX-9 from TLR and will take a 50mg test dose orally. If this is OK, I will then move on to 100mg / day dosing till I run out of product (2400mg). This last month I finished up the NSI-189 I got from the first group buy arranged by ScienceGuy, dosing 40-50mg / day. Therefore, I should have plenty of neuronal stem cells ready to mature into full neurons in the hippocampi. A couple of days ago I also received my 1.1g Dihexa from DHEXA, so I will be following the sequence introduced by sk_scientific by first using ISX-9, then moving on to the dihexa. I will try to make frequent updates. This will be such an exciting couple of weeks / months 

Edited by Megatrone, 05 September 2014 - 09:18 AM.

[drg]

Ah, I finally received my ISX-9 from TLR and will take a 50mg test dose orally. If this is OK, I will then move on to 100mg / day dosing till I run out of product (2400mg). This last month I finished up the NSI-189 I got from the first group buy arranged by ScienceGuy, dosing 40-50mg / day. Therefore, I should have plenty of neuronal stem cells ready to mature into full neurons in the hippocampi. A couple of days ago I also received my 1.1g Dihexa from DHEXA, so I will be following the sequence introduced by sk_scientific by first using ISX-9, then moving on to the dihexa. I will try to make frequent updates. This will be such an exciting couple of weeks / months 

Hows it going? 

[megatron]

 

Ah, I finally received my ISX-9 from TLR and will take a 50mg test dose orally. If this is OK, I will then move on to 100mg / day dosing till I run out of product (2400mg). This last month I finished up the NSI-189 I got from the first group buy arranged by ScienceGuy, dosing 40-50mg / day. Therefore, I should have plenty of neuronal stem cells ready to mature into full neurons in the hippocampi. A couple of days ago I also received my 1.1g Dihexa from DHEXA, so I will be following the sequence introduced by sk_scientific by first using ISX-9, then moving on to the dihexa. I will try to make frequent updates. This will be such an exciting couple of weeks / months 

Hows it going? 

 

I haven't noticed much after using it for 8 days, no positive or negative effects. Starting at day 4 I have upped the dosage to 240mg/day as I ordered 2400mg more. I'm thinking about doing 1 more week before starting dihexa. 

[drg]

Sorta disappointing to hear... I was expecting... Something :(