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SLC transporters input #343

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harishkaushikbugworks opened this issue Jun 17, 2019 · 5 comments

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@harishkaushikbugworks
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commented Jun 17, 2019

Hello,
I have 2 SLC transporters (OAT3 & MATE2-K) for which my drug is substrate from the Human HEK vesicles assay. Determined Vmax & Km from the assay, which process should i use under transporters module while building compounds. is there any need to IVIVE to calculate for whole liver

Thanks

@HenrikCordes

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commented Jun 25, 2019

Dear @harishkaushikbugworks,

could you specify what information you have in hand? Do you have information on the amount of transporter protein in the assay?
PK-Sim offers different pre-implemented transport processes you could implement in the compound building block:
image

If you can normalize you Vmax to the amount of transporter protein in the assay you could try the "in vitro acitve transport (vesicular assay). Otherwise the "specific active transport-Michaelis-Menten might be interesting for you.

Hope this helps and kind regards,

@harishkaushikbugworks

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commented Jun 25, 2019

Hello Henrik

My drug is an substrate to renal transporters in our studies OAT3 & MATE2-K with Km & Vmax as follows for MATE2-K (Vmax=111.2775 pmol/mg/min & Km =468.7402 uM) and for OAT-3 (Vmax=76.1050 pmol/mg/min & Km =120.6556 uM).
If i use the transporter protein Vmax and Km values in Transporter module then at the time simulation, how would i use both transporters values. Can you help me
I dont have information on transporter protein used in the assay.

I have used these values under Tubular Secretion – Michaelis-Menten in Renal clearance process.
So in this case which one is right and whats the approach i should take

Regards
Harish

@HenrikCordes

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commented Jun 25, 2019

Dear @harishkaushikbugworks,

I guess the pmol/mg/min are related to mg of portein/tissue in your assay? You might have to translate the mg into molecular amount before using it in PK-Sim.

You have to add the transporter expression in the individual building block and the active process in the compound building block.

It might be a good starting point for you to get familiar with the PK-Sim documentation of how to implement active process in general and how to use the expression data base to place an enzyme into a specific compartment.

Kind regards,
Henrik

@prvmalik

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commented Jun 27, 2019

It boils down to knowing:

  • The concentration of lysate protein per HEK293 cell volume (mg/uL)

  • The molar concentration of the OCT transporter in HEK293 cell volume (nmol/uL)

I'm working on the same problem but so far these numbers have evaded me. Let me know if you come up with an answer.

@harishkaushikbugworks

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commented Jul 11, 2019

Hello Henrik,
How do we convert, can you give some details
"pmol/mg/min are related to mg of portein/tissue in your assay? You might have to translate the mg into molecular amount"

@prvmalik
Did you get the values which we can use to do the above conversion and use these values

it would really help

Regards
Harish

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