ADMET TOPKAT
S. No. Compounds BBB AlogP Sol. HIA HTL HT_Prob PPB CYP2D6 PSA Ames Mut. Prob. Enrichment WOE
Novel hit molecules
01 ZINC03363328 3 0.013 3 0 0 0.05 0 0 55.83 NM 0.38 0.69 NC
02 ZINC08828920 1 2.966 3 0 0 0.29 0 0 41.43 NM 0.66 1.18 NC
03 ZINC03622539 3 0.609 4 0 0 0.17 0 0 61.70 NM 0.54 0.97 NC
04 ZINC00494463 2 1.978 3 0 0 0.42 2 0 47.05 NM 0.60 1.07 C
05 ZINC12941947 2 2.358 3 0 0 0.14 0 0 50.39 NM 0.46 0.82 NC
06 ZINC00284720 3 1.247 3 0 1 0.92 2 1 96.52 NM 0.32 0.57 NC
07 ZINC32118378 3 0.298 4 0 1 0.52 0 0 93.74 M 0.76 1.37 C
08 ZINC14183954 2 3.69 2 0 0 0.43 2 0 65.70 M 0.77 1.39 NC
09 ZINC16601509 2 2.92 3 0 1 0.77 0 1 72.77 NM 0.60 1.08 C
10 ZINC16650541 4 1.55 4 1 0 0.13 2 0 83.67 NM 0.67 1.21 NC
CAIX Inhibitors
01 Acetazolamide 4 0.088 3 0 1 0.582 0 0 113.77 NM 0.43 0.78 NC
02 Methazolamide 3 0.411 3 0 1 0.602 0 0 84.95 NM 0.72 1.29 C
03 Ethoxzolamide 3 0.355 3 0 0 0.251 0 0 103.53 NM 0.21 0.38 NC
04 Sulthiame 3 1.083 3 0 1 0.609 1 0 96.30 NM 0.16 0.28 C
05 Dichlorophenamide 3 2.918 2 0 0 0.205 2 0 87.37 NM 4.37 7.83 C
06 Dorzolamide 2 4.428 1 0 1 0.854 1 0 77.75 NM 0.37 0.66 NC
07 Brinzolamide 3 2.6 2 0 1 0.748 1 1 84.95 NM 0.45 0.82 NC
08 Indisulam 3 0.359 4 0 1 0.503 1 0 64.71 NM 0.19 0.34 NC
09 Topiramate 1 1.899 3 0 1 0.735 2 0 26.23 NM 0.62 1.12 C
10 Zonisamide 2 4.22 2 0 1 0.609 1 0 83.40 NM 0.59 1.07 NC
11 Sulpiride 4 5.084 1 1 1 0.966 2 0 93.31 NM 0.61 1.09 NC
12 Coumate 3 0.03 4 0 1 0.695 0 0 104.44 NM 0.20 0.37 NC
13 Emate 2 2.904 2 0 0 0.437 0 0 72.73 NM 0.07 0.12 C
14 Celecoxib 2 3.234 2 0 1 0.708 0 0 81.66 NM 0.52 0.94 C
15 Valdecoxib 2 3.442 2 0 0 0.45 0 0 63.80 NM 0.64 1.16 C
16 Saccharin 2 2.946 3 0 1 0.801 2 0 72.73 NM 0.48 0.86 C
17 Coumarins 4 -0.748 3 3 1 0.682 0 0 157.30 NM 0.54 0.97 NC
18 Imatinib 4 1.386 3 0 0 0.443 0 0 114.34 NM 0.53 0.96 NC
19 Nilotinib 0 3.816 2 0 1 0.834 1 0 0 M 0.76 1.37 C
20 Omeprazole 3 1.823 3 0 1 0.556 0 0 81.33 NM 0.69 1.24 NC
21 Pantoprazole 3 0.113 3 0 0 0.271 0 0 99.09 NM 0.45 0.82 NC
22 Lansoprazole 4 0.569 3 0 1 0.582 0 0 122.28 NM 0.38 0.68 NC
23 Rabeprazole  3 1.134 3 0 0 0.264 0 0 108.55 NM 0.58 1.05 NC
24 Amiloride  4 -0.307 3 0 1 0.503 0 0 120.83 NM 0.36 0.64 NC
25 Cariporide 4 1.98 2 0 1 0.721 2 0 123.60 NM 0.28 0.51 NC
BBB: Blood Brain Barrier Level; Sol.: Solubility Level; HIA: Human Intestinal Absorption Level; HTL: Hepatotoxicity Level; HepTox Prob.: Hepatotoxicity Probability; Prob.: Probability; Mut: Ames mutagen prediction; Prob.: Ames probability; Enrichment (Ames enrichment); WOE-_Prediction (weight of evidence); M: (Mutagen); NM: (Non- Mutagen); C: (Carcinogen); NC: (Non-Carcinogen). The BBB (blood brain barrier) level 0-4, having high penetration to no penetration, absorption level ideal value range from 0-1 as good to moderate, Ideal value of solubility level is 3, Hepatotoxicity probability<0.5 is ideal, similarly probability value for CYP2D6<0.5 is good and denoted with level 0, plasma protein binding value 0 is good and a compounds to accessible with BBB, AlogP value should not be greater than 3.0 and polar surface area ≤ 100 is ideal.
Table 1: Pharmacokinetics profile of CAIX inhibitors and novel hits.