NPASS Compound

Natural Product: NPC475303

Natural Product ID	NPC475303
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ebenifoline E Iii
IUPAC Name	n.a.
Synonyms	Ebenifoline E III
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL503222
PubChem CID	10102324
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives

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 118124 0 0 0 0 0 0 0 0999 V2000 4.2225 -0.3121 -2.9422 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9093 -1.2064 -1.7583 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3650 -0.5992 -0.4678 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6857 0.6830 -0.1444 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2769 1.7719 -0.0553 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3435 0.6581 0.0689 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5022 1.7641 0.4021 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4133 1.7388 -0.6136 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9806 1.5840 -0.1900 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2635 0.8226 1.1132 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0285 -0.4614 0.7591 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7636 -1.6196 1.6449 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4801 -1.6786 2.3892 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2828 -0.2616 3.0249 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0104 0.4647 1.8127 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9938 1.6105 1.8342 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5788 2.8889 2.4204 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1014 1.1655 2.5562 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7613 -0.4602 1.0342 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7521 -1.6882 1.5602 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7461 -2.7798 0.4511 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0609 -2.7451 -0.0766 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4013 -3.5751 -1.0882 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5285 -4.3404 -1.5162 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7177 -3.6469 -1.7218 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4594 -2.5428 -2.0451 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6535 -2.7483 -2.6158 N 0 0 0 0 0 0 0 0 0 0 0 0 6.1770 -3.9509 -2.8944 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4402 -5.0644 -2.5740 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2088 -4.8929 -1.9863 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8976 -2.1679 2.3871 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7223 -0.2904 3.9992 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4604 -0.1991 5.3271 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7491 -0.0820 5.7104 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5705 -0.2357 6.3143 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9254 -2.8033 0.8463 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8700 -3.7633 1.0793 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6471 -3.5779 2.0734 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9846 -4.9622 0.2172 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9372 -0.7610 -0.6197 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0265 -0.7739 -1.4790 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1584 -0.4909 -0.9463 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9404 -1.0782 -2.8780 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7391 -1.3825 -3.4640 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6407 -1.6807 -4.8150 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7672 -1.6728 -5.5882 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9853 -1.3710 -5.0263 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0695 -1.0712 -3.6574 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2259 1.6953 1.8338 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6960 1.2734 3.0792 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5922 2.1011 3.7342 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9848 3.1952 3.2505 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1079 1.6716 5.0651 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5820 2.8875 -0.1423 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5796 3.3219 -0.9567 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0261 2.5358 -1.8285 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0887 4.6775 -0.7858 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0988 5.1661 -1.5874 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5878 6.4648 -1.4243 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0728 7.2930 -0.4565 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0599 6.8118 0.3518 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5840 5.5201 0.1787 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7129 0.8993 -1.7491 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9310 1.3664 -3.0141 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8692 2.6334 -3.1810 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2307 0.4893 -4.1951 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8493 -0.2498 -0.6622 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7990 0.6849 -2.8701 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3445 -0.2979 -3.0617 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8389 -0.8278 -3.8453 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7974 -1.2761 -1.7267 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3203 -1.2785 0.3862 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1292 2.6707 0.3573 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4648 2.7810 -1.0974 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5306 1.0744 -1.0228 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1336 -0.2393 0.8940 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5662 -1.7133 2.4371 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5460 -2.4285 3.1700 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2166 -0.1577 3.5627 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2272 3.6796 1.7200 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0457 2.7746 3.3296 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5143 3.3880 2.8499 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6389 0.5948 2.0012 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6236 -3.7232 0.9832 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0677 -2.5790 -0.3530 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1601 -4.0712 -3.3630 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7876 -6.0768 -2.7645 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5775 -5.7409 -1.7090 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7166 -2.6713 1.7868 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4952 -3.0245 3.0098 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4019 -1.5135 3.0558 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1848 -0.6881 7.2597 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9403 0.7931 6.5585 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4258 -0.8309 5.9562 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9737 -5.3014 -0.0491 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5917 -5.7543 0.7044 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5032 -4.6473 -0.7111 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8521 -1.3937 -2.8787 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6826 -1.9180 -5.2562 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6762 -1.9110 -6.6576 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8622 -1.3721 -5.6615 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0600 -0.8408 -3.2721 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1989 1.7865 1.2251 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9433 2.7558 1.9329 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3988 2.5620 5.6654 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3085 1.1055 5.5603 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9822 1.0029 4.8562 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5018 4.5116 -2.3482 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3738 6.8270 -2.0574 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4601 8.3086 -0.3339 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6437 7.4498 1.1178 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7828 5.1063 0.8008 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9992 0.9628 -4.8474 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2972 0.4735 -4.7927 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4611 -0.5312 -3.8986 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4156 -1.1138 -1.0263 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9330 0.6324 -1.2981 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2446 0.0284 0.3495 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 4 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 16 18 1 0 15 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 20 31 1 0 14 32 1 0 32 33 1 0 33 34 2 0 33 35 1 0 12 36 1 0 36 37 1 0 37 38 2 0 37 39 1 0 11 40 1 0 40 41 1 0 41 42 2 0 41 43 1 0 43 44 2 0 44 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 10 49 1 0 49 50 1 0 50 51 1 0 51 52 2 0 51 53 1 0 9 54 1 0 54 55 1 0 55 56 2 0 55 57 1 0 57 58 2 0 58 59 1 0 59 60 2 0 60 61 1 0 61 62 2 0 8 63 1 0 63 64 1 0 64 65 2 0 64 66 1 0 3 67 1 0 26 2 1 0 16 7 1 0 15 10 1 0 20 13 1 0 30 25 1 0 48 43 1 0 62 57 1 0 1 68 1 0 1 69 1 0 1 70 1 0 2 71 1 0 3 72 1 0 7 73 1 0 8 74 1 0 9 75 1 0 11 76 1 0 12 77 1 0 13 78 1 0 14 79 1 0 17 80 1 0 17 81 1 0 17 82 1 0 18 83 1 0 21 84 1 0 21 85 1 0 28 86 1 0 29 87 1 0 30 88 1 0 31 89 1 0 31 90 1 0 31 91 1 0 35 92 1 0 35 93 1 0 35 94 1 0 39 95 1 0 39 96 1 0 39 97 1 0 44 98 1 0 45 99 1 0 46100 1 0 47101 1 0 48102 1 0 49103 1 0 49104 1 0 53105 1 0 53106 1 0 53107 1 0 58108 1 0 59109 1 0 60110 1 0 61111 1 0 62112 1 0 66113 1 0 66114 1 0 66115 1 0 67116 1 0 67117 1 0 67118 1 0 M END

Standard InCHIKey	CLGCPUMGHCEASW-ORWJBWFWSA-N
Standard InCHI	InChI=1S/C48H51NO18/c1-24-25(2)41(54)64-38-36(62-28(5)52)40(66-43(56)31-18-13-10-14-19-31)47(23-59-26(3)50)39(65-42(55)30-16-11-9-12-17-30)35(61-27(4)51)33-37(63-29(6)53)48(47,46(38,8)58)67-45(33,7)22-60-44(57)32-20-15-21-49-34(24)32/h9-21,24-25,33,35-40,58H,22-23H2,1-8H3/t24?,25?,33-,35-,36+,37-,38+,39-,40+,45+,46+,47-,48+/m1/s1
SMILES	CC1C(C(=O)OC2C(C(C3(C(C(C4C(C3(C2(C)O)OC4(COC(=O)C5=C1N=CC=C5)C)OC(=O)C)OC(=O)C)OC(=O)C6=CC=CC=C6)COC(=O)C)OC(=O)C7=CC=CC=C7)OC(=O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	929.31	Volume:	903.27 ? Van der Waals volume.
Dense:	1.029	LogP:	2.051 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.302 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.798 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	49.0
TPSA:	252.75 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	1.0	Rings:	7.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.238	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.615	Fsp³:	0.479
MCE-18:	237.296 ? 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:	0.447	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.303 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.024	Promiscuous compounds:	0.015

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.413	MDCK Permeability:	-4.814
Pgp-inhibitor:	0.997	Pgp-substrate:	0.307
PAMPA:	0.973 ? 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):	0.0
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.398
50% Bioavailability (F50%):	0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	1.0
Plasma Protein Binding (PPB):	76.536%	Volume Distribution (VD):	-0.24
Fu:	23.527% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.604
OATP1B3 inhibitor:	0.95	BCRP inhibitor:	0.0
BSEP inhibitor:	0.999

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:	0.007
CYP3A4-inhibitor:	0.14	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? 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):

-0.16

Half-life (T1/2):

1.62

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.38
Human Hepatotoxicity (H-HT):	0.146	Drug-induced Liver Injury (DILI):	0.995
AMES Toxicity:	0.535	Rat Oral Acute Toxicity:	0.021
Maximum Recommended Daily Dose:	0.282	Skin Sensitization:	0.992
Carcinogencity:	0.738	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.0
Drug-induced Neurotoxicity:	0.763	Ototoxicity:	0.922
Hematotoxicity:	0.03	Drug-induced Nephrotoxicity:	0.93
Genotoxicity:	0.785	RPMI-8226 Immunitoxicity:	0.122
A549 Cytotoxicity:	0.018	Hek293 Cytotoxicity:	0.558
BCF:	0.836 ? 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:	3.909 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.912 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.443 ? 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
NPO14242	Maytenus laevis	Species	Celastraceae	Eukaryota	bark	Leticia, Colombia	n.a.	PMID[15568791]
NPO14242	Maytenus laevis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14242	Maytenus laevis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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
Activity	6

Activity Type	# Activity
Cell line	6

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
NPT927	Cell line	PBMC	Homo sapiens	Activity	<	7.8	pg/ml	PMID[24904961]

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 NPC475303 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	22451
0.1-0.2	26051
0.2-0.3	1056
0.3-0.4	200
0.4-0.5	29
0.5-0.6	19
0.6-0.7	22
0.7-0.8	0
0.8-0.85	4
0.85-0.9	2
0.9-0.95	4
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9778	High Similarity	NPC476110
0.9348	High Similarity	NPC475596
0.9032	High Similarity	NPC87152
0.9032	High Similarity	NPC475600
0.9032	High Similarity	NPC475631
0.8571	High Similarity	NPC76565
0.8571	High Similarity	NPC601313
0.8113	Intermediate Similarity	NPC482915
0.8081	Intermediate Similarity	NPC475644
0.8039	Intermediate Similarity	NPC327769
0.8019	Intermediate Similarity	NPC483854
0.7857	Intermediate Similarity	NPC326930
0.7843	Intermediate Similarity	NPC477787
0.7778	Intermediate Similarity	NPC475301
0.7723	Intermediate Similarity	NPC30456
0.7723	Intermediate Similarity	NPC488904
0.7525	Intermediate Similarity	NPC316841
0.7264	Intermediate Similarity	NPC327904
0.7255	Intermediate Similarity	NPC122968
0.7255	Intermediate Similarity	NPC328186
0.7255	Intermediate Similarity	NPC228377
0.7196	Intermediate Similarity	NPC483853
0.7196	Intermediate Similarity	NPC608314
0.7184	Intermediate Similarity	NPC470486
0.7143	Intermediate Similarity	NPC35208
0.71	Intermediate Similarity	NPC475498
0.7075	Intermediate Similarity	NPC475406
0.7019	Intermediate Similarity	NPC471977
0.7009	Intermediate Similarity	NPC319880
0.7009	Intermediate Similarity	NPC320324
0.6944	Remote Similarity	NPC328928
0.6916	Remote Similarity	NPC244839
0.6909	Remote Similarity	NPC475426
0.6822	Remote Similarity	NPC473689
0.6822	Remote Similarity	NPC292416
0.68	Remote Similarity	NPC250807
0.68	Remote Similarity	NPC57797
0.6789	Remote Similarity	NPC38959
0.6783	Remote Similarity	NPC483855
0.6754	Remote Similarity	NPC483856
0.6636	Remote Similarity	NPC471190
0.6569	Remote Similarity	NPC475137
0.6381	Remote Similarity	NPC146824
0.6381	Remote Similarity	NPC473833
0.6262	Remote Similarity	NPC53255
0.6262	Remote Similarity	NPC85879
0.6239	Remote Similarity	NPC477788
0.6168	Remote Similarity	NPC473506
0.6161	Remote Similarity	NPC475648
0.6058	Remote Similarity	NPC470306
0.6018	Remote Similarity	NPC600583
0.6018	Remote Similarity	NPC601643
0.5946	Remote Similarity	NPC328154
0.5893	Remote Similarity	NPC13603
0.5877	Remote Similarity	NPC253482
0.5726	Remote Similarity	NPC471979
0.5714	Remote Similarity	NPC475533
0.5641	Remote Similarity	NPC170751
0.5517	Remote Similarity	NPC483893
0.5505	Remote Similarity	NPC471016
0.5398	Remote Similarity	NPC475362
0.5385	Remote Similarity	NPC483894
0.5345	Remote Similarity	NPC324619
0.5339	Remote Similarity	NPC237702
0.52	Remote Similarity	NPC51602
0.5135	Remote Similarity	NPC473850
0.5128	Remote Similarity	NPC475315
0.5126	Remote Similarity	NPC600607
0.5126	Remote Similarity	NPC611166
0.5085	Remote Similarity	NPC600224
0.5043	Remote Similarity	NPC607403

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475303 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4386
0.1-0.2	4719
0.2-0.3	44
0.3-0.4	1
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