Case Studies for CPCA Scoring

Let’s try CPCA Scoring!! If you want to post cases, the following PDF may be available to convert and custom. And images of compounds may be available in the visualization thread. And you can request the scoring, and then someone may help you.

Example of CPCA Scoring.pdf (71.4 KB)

I’m not sure I can respond to all requests correctly. I’m looking forward to your participation!! :grinning:


The compound is with 6-membered ring. Is it right? Read-acorss looks better.


Thank you very much Yosukemino

Yes, it is for acyclic N-nitroso groups and wanted re-confirm the same.


Please tell us how this structure’s alpha hydrogen is +1.

Hi, @Dinkar

Thank you for asking me. The compound has two alfa-hydrogens on both sides. The alfa-hydrogen score of (2,2) is +1.

Dear Sir,

I appreciate your prompt reply.

I still have the same query: how is Q & A quote +1 if there is 2+2 alfa hydrogen in the structure?

Thank you once more for your assistance and advice.


Thank you for asking, @Dinkar. As we discussed in the Q&A thread, the score is determined from knowledge of SAR. The structure (2,2) is easiliy affected by CYP activation compared to (1, 2) and (1,3) due to the steric hindrance. And I guess this scoring system is validated with data in LCDB.

So I am not sure why the structure (2,2) is score+1 but I guess it’s reasonable.

Dear Sir,

Many thanks for your prompt response, which is valuable and helpful to us.

Dr. Dinkar Gagare

1 Like

I calculated the score of N-nitroso-vonoprazan. Strict AI should be set for the compound. What do you think about it, guys?

1 Like

I add the example of NTTP(7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo-[4,3- a]pyrazine) @David posted.

The AI of NTTP and NNV(nitroso-varenicline) are both calculated from the AI of NTHP by the read-across method. Though NTTP has the activating feature, NNV has no activating feature. But the score of NNV is 2, the same as that of NTTP. It’s interesting.


The score of NNV: ((2,2) for H-count = 1, In a 7-membered ring = 1, Total2, limit 100 ng/day).




NNV is actually complex to assign, because of its fused bicyclic system - the nitrosamine is both in a 6- and 7-membered ring, and in this case, per the guidance, the smaller ring takes precedence - so I would say it gets 3 points: 6-membered ring and (2,2) for hydrogen count, i.e. a limit of 400!

However with a compound-specific AI in the guidance, I assume that takes precedence, otherwise there’s a full order of magnitude to play with.


Dear @David,

Thank you for pointing it out. Yes, you are right. The feature score for only the smallest matching
ring should be applied.

The score of NNV: ((2,2) for H-count = 1, In a 6-membered ring = 2, Total3, limit 400 ng/day).

And the current AI of 37 ng/day represents less than 10% of the AI of 400 ng/day. When CPCA becomes available on NNV, it means that varenicline is free from control for NNV. And the surrogate compound of NTHP for NNV looks controversial due to the size of the ring and the position of sp2 carbon. I anticipate the update of the AI list in the future.

1 Like