NPASS Compound

Natural Product: NPC320324

Natural Product ID	NPC320324
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ZOOHSIOMIRBBDY-YYEQAJDZSA-N
IUPAC Name	n.a.
Synonyms	7-Epimekongensine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1813069
PubChem CID	56662792
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 117122 0 0 0 0 0 0 0 0999 V2000 -5.2506 -3.2498 0.2631 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5872 -2.1381 -0.4513 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0852 -1.5333 -1.4212 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3312 -1.7317 -0.0247 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6640 -0.6380 -0.7088 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3456 -0.4612 0.0304 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7835 -0.1282 1.4535 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3122 1.2832 1.5861 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4622 2.3458 0.9983 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3412 2.0009 -0.5351 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5858 0.7655 -0.4048 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4125 0.3886 -1.4834 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3316 -0.5817 -0.6917 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6176 -1.8759 -0.8520 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6141 -1.7336 0.0474 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3612 -2.8989 -0.2154 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3677 -3.9583 0.6373 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6889 -3.9052 1.6925 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1857 -5.1762 0.3039 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3347 -2.2925 -2.1397 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8124 -3.4967 -2.6645 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5304 -4.2599 -1.9723 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4490 -3.8525 -4.0647 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6298 -0.4200 -0.7509 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6877 -0.4541 -1.5269 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5093 -0.7555 -2.7358 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1015 -0.1427 -1.0083 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1742 1.2329 -0.4483 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4224 1.6097 0.7558 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9170 1.1209 2.0634 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1751 1.0632 3.2160 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8069 0.5927 4.3581 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1258 0.1937 4.3686 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8400 0.2655 3.2013 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2205 0.7181 2.1122 N 0 0 0 0 0 0 0 0 0 0 0 0 2.7923 1.4880 3.3806 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3209 1.6744 4.5626 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8856 1.7284 2.3938 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5224 2.1564 2.6580 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0219 2.2643 1.2454 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3143 1.0778 0.6575 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6520 3.5013 0.6884 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3410 -1.1723 0.0629 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0138 -0.2324 -2.0761 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2517 -1.3337 -2.8584 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5863 -2.3664 -2.6012 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2624 -1.3140 -3.9759 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2577 1.4530 -2.0286 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1761 -0.2857 -2.5279 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5202 2.0815 -1.2008 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7606 2.9680 -2.2090 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8321 3.7657 -2.5467 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0199 3.0671 -2.9359 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2107 3.9780 -3.9402 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3943 4.0851 -4.6405 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4377 3.2437 -4.3242 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2736 2.3081 -3.3087 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0682 2.2288 -2.6254 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5667 1.4719 2.9686 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8367 1.6493 3.4947 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7898 1.6336 2.6557 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0961 1.8472 4.9401 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8155 -0.9750 1.9177 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6982 -1.7850 3.0389 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5849 -1.7307 3.6593 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7808 -2.6839 3.5310 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5809 -3.7558 0.9814 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0806 -2.8348 0.9104 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6539 -4.0235 -0.4223 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5564 -0.9519 -1.7407 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3923 0.1749 -0.5323 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9149 -0.3063 2.1086 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3088 1.3154 1.1047 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9349 3.3136 1.1100 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6574 2.7784 -0.9811 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0852 -0.3804 0.4660 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2581 -2.6598 -0.3716 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1689 -1.8742 1.0807 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8673 -5.4191 1.1479 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4849 -6.0474 0.1609 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7780 -5.0104 -0.6099 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6175 -3.0024 -4.7540 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0328 -4.7402 -4.3926 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6221 -4.1181 -4.0489 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2978 1.4500 -0.3260 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9315 1.9327 -1.3235 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3622 1.2636 0.6267 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3092 2.7379 0.8105 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2098 0.5397 5.2936 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5691 -0.1652 5.2868 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9019 -0.0457 3.1730 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0067 1.5214 3.3369 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5631 3.1766 3.0786 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5380 3.3108 0.0820 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0628 4.1586 1.5315 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0816 4.2233 0.2203 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6393 -1.0551 0.9213 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3793 -1.3182 0.3569 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0532 -2.1823 -0.4061 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1769 -0.7679 -3.6659 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8609 -0.7964 -4.8680 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5673 -2.3497 -4.1732 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5965 1.1285 -3.0635 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8170 2.4387 -2.2095 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2309 1.5229 -1.4679 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5182 0.3375 -3.1949 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3914 4.6516 -4.2005 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5213 4.8116 -5.4294 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3993 3.2571 -4.8197 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0588 1.6178 -3.0134 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9400 1.5031 -1.8381 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4163 1.2288 5.5575 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1718 1.5797 5.1496 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9314 2.9075 5.2491 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6284 -3.7386 3.1964 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7519 -2.2858 3.2121 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6903 -2.7416 4.6559 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 17 19 1 0 14 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 13 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 31 36 1 0 36 37 2 0 36 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 40 42 1 0 27 43 1 0 27 44 1 0 44 45 1 0 45 46 2 0 45 47 1 0 12 48 1 0 12 49 1 0 10 50 1 0 50 51 1 0 51 52 2 0 51 53 1 0 53 54 2 0 54 55 1 0 55 56 2 0 56 57 1 0 57 58 2 0 8 59 1 0 59 60 1 0 60 61 2 0 60 62 1 0 7 63 1 0 63 64 1 0 64 65 2 0 64 66 1 0 11 6 1 0 15 6 1 0 40 9 1 0 41 11 1 0 35 30 1 0 58 53 1 0 1 67 1 0 1 68 1 0 1 69 1 0 5 70 1 0 5 71 1 0 7 72 1 0 8 73 1 0 9 74 1 0 10 75 1 0 13 76 1 0 14 77 1 0 15 78 1 0 19 79 1 0 19 80 1 0 19 81 1 0 23 82 1 0 23 83 1 0 23 84 1 0 28 85 1 0 28 86 1 0 29 87 1 0 29 88 1 0 32 89 1 0 33 90 1 0 34 91 1 0 39 92 1 0 39 93 1 0 42 94 1 0 42 95 1 0 42 96 1 0 43 97 1 0 43 98 1 0 43 99 1 0 47100 1 0 47101 1 0 47102 1 0 48103 1 0 48104 1 0 48105 1 0 49106 1 0 54107 1 0 55108 1 0 56109 1 0 57110 1 0 58111 1 0 62112 1 0 62113 1 0 62114 1 0 66115 1 0 66116 1 0 66117 1 0 M END

Standard InCHIKey	ZOOHSIOMIRBBDY-YYEQAJDZSA-N
Standard InCHI	InChI=1S/C45H51NO20/c1-22(47)57-21-44-36(61-25(4)50)32(59-23(2)48)31-34(63-38(53)28-14-11-10-12-15-28)45(44)43(9,56)35(33(60-24(3)49)37(44)62-26(5)51)64-40(55)41(7,65-27(6)52)18-17-30-29(16-13-19-46-30)39(54)58-20-42(31,8)66-45/h10-16,19,31-37,56H,17-18,20-21H2,1-9H3/t31-,32+,33+,34-,35+,36-,37+,41+,42+,43+,44+,45+/m1/s1
SMILES	CC(=O)OCC12C(C(C3C(C14C(C(C(C2OC(=O)C)OC(=O)C)OC(=O)C(CCC5=C(C=CC=N5)C(=O)OCC3(O4)C)(C)OC(=O)C)(C)O)OC(=O)C6=CC=CC=C6)OC(=O)C)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	925.3	Volume:	882.791 ? Van der Waals volume.
Dense:	1.048	LogP:	1.287 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.62 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.162 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	45.0
TPSA:	279.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	21.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	21.0

MedChem Properties

QED Drug-Likeness Score:	0.277	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.733	Fsp³:	0.556
MCE-18:	230.286 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.06	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.178 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.01	Promiscuous compounds:	0.006

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.089	MDCK Permeability:	-4.564
Pgp-inhibitor:	0.864	Pgp-substrate:	0.855
PAMPA:	0.996 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.565
50% Bioavailability (F50%):	0.918

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	1.0
Plasma Protein Binding (PPB):	61.514%	Volume Distribution (VD):	-0.438
Fu:	33.73% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.407
OATP1B3 inhibitor:	0.918	BCRP inhibitor:	0.0
BSEP inhibitor:	0.975

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.393	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.737 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

0.041

Half-life (T1/2):

1.64

ADMET: Toxicity

hERG Blockers:	0.008	hERG Blockers (10um):	0.11
Human Hepatotoxicity (H-HT):	0.344	Drug-induced Liver Injury (DILI):	0.982
AMES Toxicity:	0.83	Rat Oral Acute Toxicity:	0.091
Maximum Recommended Daily Dose:	0.381	Skin Sensitization:	0.998
Carcinogencity:	0.704	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.0
Drug-induced Neurotoxicity:	0.448	Ototoxicity:	0.825
Hematotoxicity:	0.125	Drug-induced Nephrotoxicity:	0.939
Genotoxicity:	0.992	RPMI-8226 Immunitoxicity:	0.123
A549 Cytotoxicity:	0.004	Hek293 Cytotoxicity:	0.112
BCF:	0.55 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.48 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.679 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.01 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO30152	Maytenus mekongensis	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[21634414]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Organism	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	3900.0	nM	PMID[21634414]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC320324 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	18271
0.1-0.2	30185
0.2-0.3	1081
0.3-0.4	224
0.4-0.5	26
0.5-0.6	25
0.6-0.7	21
0.7-0.8	0
0.8-0.85	1
0.85-0.9	2
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC319880
0.9688	High Similarity	NPC327904
0.9286	High Similarity	NPC38959
0.87	High Similarity	NPC244839
0.8571	High Similarity	NPC328186
0.83	Intermediate Similarity	NPC316841
0.7981	Intermediate Similarity	NPC600583
0.7843	Intermediate Similarity	NPC122968
0.7843	Intermediate Similarity	NPC228377
0.781	Intermediate Similarity	NPC601643
0.7767	Intermediate Similarity	NPC475631
0.7547	Intermediate Similarity	NPC473689
0.7547	Intermediate Similarity	NPC292416
0.7524	Intermediate Similarity	NPC475596
0.74	Intermediate Similarity	NPC250807
0.74	Intermediate Similarity	NPC57797
0.7315	Intermediate Similarity	NPC475406
0.7273	Intermediate Similarity	NPC471979
0.7264	Intermediate Similarity	NPC87152
0.7196	Intermediate Similarity	NPC476110
0.7156	Intermediate Similarity	NPC237702
0.7117	Intermediate Similarity	NPC327769
0.7115	Intermediate Similarity	NPC146824
0.7103	Intermediate Similarity	NPC475600
0.7009	Intermediate Similarity	NPC475303
0.6937	Remote Similarity	NPC477787
0.6822	Remote Similarity	NPC53255
0.6822	Remote Similarity	NPC85879
0.6757	Remote Similarity	NPC600607
0.6757	Remote Similarity	NPC611166
0.6667	Remote Similarity	NPC76565
0.6667	Remote Similarity	NPC601313
0.6577	Remote Similarity	NPC13603
0.6549	Remote Similarity	NPC253482
0.6545	Remote Similarity	NPC475301
0.6518	Remote Similarity	NPC30456
0.6518	Remote Similarity	NPC488904
0.6261	Remote Similarity	NPC475648
0.6228	Remote Similarity	NPC475644
0.6161	Remote Similarity	NPC326930
0.6154	Remote Similarity	NPC328928
0.6148	Remote Similarity	NPC483854
0.6121	Remote Similarity	NPC600546
0.6098	Remote Similarity	NPC482915
0.6053	Remote Similarity	NPC470486
0.6	Remote Similarity	NPC600224
0.5963	Remote Similarity	NPC473850
0.5929	Remote Similarity	NPC475362
0.5913	Remote Similarity	NPC328154
0.5862	Remote Similarity	NPC604935
0.5776	Remote Similarity	NPC471977
0.5702	Remote Similarity	NPC483853
0.5702	Remote Similarity	NPC608314
0.5676	Remote Similarity	NPC35208
0.5641	Remote Similarity	NPC477788
0.563	Remote Similarity	NPC483893
0.5625	Remote Similarity	NPC471016
0.561	Remote Similarity	NPC475426
0.5586	Remote Similarity	NPC470306
0.55	Remote Similarity	NPC483894
0.5424	Remote Similarity	NPC475533
0.5391	Remote Similarity	NPC483856
0.5391	Remote Similarity	NPC475498
0.5351	Remote Similarity	NPC475137
0.5333	Remote Similarity	NPC471190
0.5333	Remote Similarity	NPC324619
0.5294	Remote Similarity	NPC607403
0.525	Remote Similarity	NPC475315
0.5214	Remote Similarity	NPC483892
0.5085	Remote Similarity	NPC473833
0.5082	Remote Similarity	NPC483895

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC320324 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3646
0.1-0.2	5452
0.2-0.3	50
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data