NPASS Compound

Natural Product: NPC298107

Natural Product ID	NPC298107
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BLVUULSAXPAVHB-JWKXWJMNSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44255062
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001013] Steroidal glycosides [CHEMONTID:0002364] Steroidal saponins

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 115122 0 0 0 0 0 0 0 0999 V2000 11.8458 0.0602 2.9197 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7577 -0.1737 1.9199 C 0 0 2 0 0 0 0 0 0 0 0 0 10.5261 0.9853 0.9918 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1653 1.6132 1.1828 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0737 0.6130 1.3161 C 0 0 2 0 0 0 0 0 0 0 0 0 7.3761 0.3447 -0.0276 C 0 0 1 0 0 0 0 0 0 0 0 0 8.2139 -0.4933 -0.9309 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1521 -0.4153 0.4989 C 0 0 1 0 0 0 0 0 0 0 0 0 5.9058 0.3472 1.8055 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6056 1.1181 1.5224 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8880 0.1375 0.6780 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7015 0.6349 -0.0890 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6301 1.1642 0.8727 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4293 1.6292 0.1228 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1025 0.6618 -0.8775 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1087 -0.2451 -0.2371 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8491 -1.0996 -1.2214 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1313 -1.0903 -2.5517 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3406 -1.3097 -2.2760 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9584 -0.0785 -1.6473 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4452 0.8647 -2.7252 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1025 -0.5462 -0.8001 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0507 -1.3879 -1.5628 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4427 -1.4249 -1.0291 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1697 -2.3930 -1.1248 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9443 -0.2215 -0.3566 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1196 0.8613 -1.3944 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1629 -0.6945 -1.4413 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0890 -1.7128 -1.1681 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9863 -1.3475 -0.0543 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.3435 -0.8536 -0.3950 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.6440 -0.9858 -1.8645 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0318 -2.3345 -2.2748 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5751 -2.6581 -3.6356 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9575 -2.8593 -3.5487 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6837 -2.1349 -2.3373 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9550 -0.0236 -2.5945 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6117 0.4240 0.0867 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6519 0.4606 0.9961 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.3240 1.1349 2.2862 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.5101 0.9798 3.2164 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.7079 1.5969 2.5294 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.8583 1.1008 1.1096 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.8991 1.9692 0.4349 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4764 3.2830 0.4271 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6757 1.2239 0.3860 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.8434 1.2176 3.2441 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2586 1.6305 4.4016 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2244 0.5951 2.9325 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0376 -2.3947 0.8973 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9770 1.1671 2.0180 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4330 -0.6121 1.8153 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5017 -0.5604 2.6730 C 0 0 0 0 0 0 0 0 0 0 0 0 12.1451 -0.9335 3.3337 H 0 0 0 0 0 0 0 0 0 0 0 0 11.4284 0.6361 3.7869 H 0 0 0 0 0 0 0 0 0 0 0 0 12.7272 0.5391 2.4670 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0258 -1.0560 1.2950 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6341 0.6958 -0.0651 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2807 1.7732 1.2446 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2283 2.2826 2.0780 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9668 2.2314 0.2632 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1132 1.3367 -0.4156 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9745 -1.0193 -0.3158 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7927 0.2064 -1.5964 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6119 -1.1962 -1.5430 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4348 -1.4494 0.6885 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6996 -0.3562 2.6441 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8491 2.0615 1.0375 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0885 1.3523 2.4834 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6839 -0.7751 1.2664 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0221 1.4580 -0.7214 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4122 0.3218 1.5595 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0570 2.0408 1.4121 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3872 1.7962 0.8844 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6392 2.6281 -0.3151 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6757 1.2663 -1.6416 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8474 0.3968 0.2864 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6515 -0.8791 0.5629 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8307 -2.1677 -0.8700 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4733 -1.9865 -3.1401 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3160 -0.1549 -3.1095 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4060 -2.1747 -1.5767 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9143 -1.5696 -3.1809 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5338 1.1281 -3.3208 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7965 1.8275 -2.2898 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2550 0.4797 -3.3430 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6503 -1.1821 0.0262 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6953 -2.4607 -1.4947 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1305 -1.1981 -2.6401 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1807 1.8666 -0.9658 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3032 0.7535 -2.1383 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0481 0.5732 -1.9706 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4600 -2.5911 -0.8328 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4778 -0.5115 0.5160 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0895 -1.5277 0.1224 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7074 -1.0482 -2.0938 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3690 -3.0619 -1.5186 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0969 -3.5372 -4.1023 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4418 -1.7884 -4.3213 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1856 -3.7380 -3.1428 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5270 0.7404 -2.8698 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1025 -0.5223 1.1971 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1814 2.2345 2.1557 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7488 -0.0931 3.3717 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6133 2.6942 2.5781 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2106 0.0610 1.1147 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8000 1.9347 1.1122 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1913 1.5817 -0.5583 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5031 3.3292 0.2513 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1414 0.3454 2.8805 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8460 2.4368 4.4693 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3822 -0.3289 3.1897 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4201 -2.0929 1.7490 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6076 -1.5539 3.1421 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2841 0.1769 3.4731 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 1 0 5 6 1 0 6 7 1 0 6 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 1 0 18 19 1 0 19 20 1 0 20 21 1 6 20 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 6 17 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 33 36 1 0 32 37 1 0 31 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 43 46 1 0 42 47 1 0 41 48 1 0 40 49 1 0 30 50 1 0 9 51 1 0 5 52 1 1 52 53 1 0 53 2 1 0 51 5 1 0 26 8 1 0 36 29 1 0 46 39 1 0 26 11 1 0 22 12 1 0 20 15 1 0 1 54 1 0 1 55 1 0 1 56 1 0 2 57 1 6 3 58 1 0 3 59 1 0 4 60 1 0 4 61 1 0 6 62 1 6 7 63 1 0 7 64 1 0 7 65 1 0 8 66 1 1 9 67 1 1 10 68 1 0 10 69 1 0 11 70 1 1 12 71 1 6 13 72 1 0 13 73 1 0 14 74 1 0 14 75 1 0 15 76 1 6 16 77 1 0 16 78 1 0 17 79 1 1 18 80 1 0 18 81 1 0 19 82 1 0 19 83 1 0 21 84 1 0 21 85 1 0 21 86 1 0 22 87 1 1 23 88 1 0 23 89 1 0 27 90 1 0 27 91 1 0 27 92 1 0 29 93 1 1 30 94 1 1 31 95 1 1 32 96 1 1 33 97 1 1 34 98 1 0 34 99 1 0 35100 1 0 37101 1 0 39102 1 1 40103 1 6 41104 1 1 42105 1 6 43106 1 1 44107 1 0 44108 1 0 45109 1 0 47110 1 0 48111 1 0 49112 1 0 50113 1 0 53114 1 0 53115 1 0 M END

Standard InCHIKey	BLVUULSAXPAVHB-JWKXWJMNSA-N
Standard InCHI	InChI=1S/C39H62O14/c1-17-7-10-39(48-16-17)18(2)28-24(53-39)12-23-21-6-5-19-11-20(8-9-37(19,3)22(21)13-27(42)38(23,28)4)49-36-33(47)34(30(44)26(15-41)51-36)52-35-32(46)31(45)29(43)25(14-40)50-35/h17-26,28-36,40-41,43-47H,5-16H2,1-4H3/t17-,18+,19-,20+,21-,22+,23+,24+,25-,26-,28+,29-,30+,31+,32-,33-,34+,35+,36-,37+,38-,39-/m1/s1
SMILES	C[C@@H]1CC[C@@]2([C@@H](C)[C@H]3[C@H](C[C@H]4[C@@H]5CC[C@@H]6C[C@H](CC[C@]6(C)[C@H]5CC(=O)[C@]34C)O[C@H]3[C@@H]([C@H]([C@H]([C@@H](CO)O3)O)O[C@H]3[C@@H]([C@H]([C@@H]([C@@H](CO)O3)O)O)O)O)O2)OC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	754.41	Volume:	735.075 ? Van der Waals volume.
Dense:	1.026	LogP:	1.54 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.239 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.955 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	43.0
TPSA:	214.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	7.0	Rings:	8.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.185	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.326	Fsp³:	0.974
MCE-18:	203.052 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.73	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.182	Promiscuous compounds:	0.176

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.989	MDCK Permeability:	-5.101
Pgp-inhibitor:	0.043	Pgp-substrate:	0.172
PAMPA:	0.906 ? 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):	0.001
20% Bioavailability (F20%):	0.025	30% Bioavailability (F30%):	0.931
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.079
Plasma Protein Binding (PPB):	52.341%	Volume Distribution (VD):	-0.46
Fu:	45.069% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.37
BSEP inhibitor:	0.751

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.991	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.993	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.812
HLM stability:	0.728 ? 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):

1.001

Half-life (T1/2):

2.316

ADMET: Toxicity

hERG Blockers:	0.021	hERG Blockers (10um):	0.054
Human Hepatotoxicity (H-HT):	0.706	Drug-induced Liver Injury (DILI):	0.993
AMES Toxicity:	0.969	Rat Oral Acute Toxicity:	0.038
Maximum Recommended Daily Dose:	0.054	Skin Sensitization:	1.0
Carcinogencity:	0.307	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.01
Drug-induced Neurotoxicity:	0.013	Ototoxicity:	0.996
Hematotoxicity:	0.498	Drug-induced Nephrotoxicity:	0.777
Genotoxicity:	0.024	RPMI-8226 Immunitoxicity:	0.311
A549 Cytotoxicity:	0.983	Hek293 Cytotoxicity:	0.954
BCF:	1.069 ? 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:	3.261 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.451 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.769 ? 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
NPO16699	Agave utahensis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19645463]
NPO16699	Agave utahensis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16699	Agave utahensis	Species	Asparagaceae	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

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

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 NPC298107 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	25353
0.1-0.2	21448
0.2-0.3	2585
0.3-0.4	288
0.4-0.5	101
0.5-0.6	48
0.6-0.7	25
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8256	Intermediate Similarity	NPC234352
0.781	Intermediate Similarity	NPC220836
0.7708	Intermediate Similarity	NPC92890
0.7524	Intermediate Similarity	NPC94086
0.7524	Intermediate Similarity	NPC473817
0.74	Intermediate Similarity	NPC475319
0.734	Intermediate Similarity	NPC215408
0.7143	Intermediate Similarity	NPC233433
0.6961	Remote Similarity	NPC184617
0.6634	Remote Similarity	NPC202898
0.6596	Remote Similarity	NPC297348
0.6596	Remote Similarity	NPC325828
0.6596	Remote Similarity	NPC249204
0.6596	Remote Similarity	NPC48339
0.6596	Remote Similarity	NPC141769
0.6596	Remote Similarity	NPC477547
0.6514	Remote Similarity	NPC132080
0.6495	Remote Similarity	NPC206003
0.6495	Remote Similarity	NPC473610
0.6481	Remote Similarity	NPC108072
0.6449	Remote Similarity	NPC475625
0.63	Remote Similarity	NPC107962
0.6289	Remote Similarity	NPC477451
0.6275	Remote Similarity	NPC14704
0.6263	Remote Similarity	NPC211354
0.6263	Remote Similarity	NPC107188
0.6239	Remote Similarity	NPC232037
0.6186	Remote Similarity	NPC305771
0.6186	Remote Similarity	NPC94072
0.6186	Remote Similarity	NPC169816
0.6182	Remote Similarity	NPC470864
0.6078	Remote Similarity	NPC6295
0.6058	Remote Similarity	NPC475351
0.5962	Remote Similarity	NPC160426
0.5932	Remote Similarity	NPC15918
0.5918	Remote Similarity	NPC177834
0.5913	Remote Similarity	NPC470866
0.5876	Remote Similarity	NPC485594
0.5872	Remote Similarity	NPC97700
0.5872	Remote Similarity	NPC30856
0.5847	Remote Similarity	NPC273002
0.5843	Remote Similarity	NPC161035
0.5843	Remote Similarity	NPC170438
0.5784	Remote Similarity	NPC19400
0.5743	Remote Similarity	NPC250393
0.5657	Remote Similarity	NPC181845
0.5652	Remote Similarity	NPC480553
0.5636	Remote Similarity	NPC128572
0.5619	Remote Similarity	NPC125324
0.5545	Remote Similarity	NPC249553
0.5545	Remote Similarity	NPC294686
0.5545	Remote Similarity	NPC182900
0.55	Remote Similarity	NPC473505
0.5478	Remote Similarity	NPC480554
0.5431	Remote Similarity	NPC476112
0.5431	Remote Similarity	NPC307534
0.5364	Remote Similarity	NPC475643
0.5354	Remote Similarity	NPC24960
0.5304	Remote Similarity	NPC116756
0.5288	Remote Similarity	NPC222731
0.5268	Remote Similarity	NPC51172
0.5268	Remote Similarity	NPC49032
0.5254	Remote Similarity	NPC92297
0.5188	Remote Similarity	NPC481189
0.5169	Remote Similarity	NPC470862
0.5164	Remote Similarity	NPC480556
0.5143	Remote Similarity	NPC474399
0.5138	Remote Similarity	NPC195297
0.5135	Remote Similarity	NPC473601
0.5133	Remote Similarity	NPC471464
0.5133	Remote Similarity	NPC300557
0.5116	Remote Similarity	NPC481190
0.5096	Remote Similarity	NPC131693
0.5096	Remote Similarity	NPC475436
0.5091	Remote Similarity	NPC113044
0.5091	Remote Similarity	NPC283829
0.5091	Remote Similarity	NPC161676
0.5086	Remote Similarity	NPC470863
0.5051	Remote Similarity	NPC277715
0.5046	Remote Similarity	NPC485595
0.5044	Remote Similarity	NPC477809

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC298107 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7472
0.1-0.2	1607
0.2-0.3	62
0.3-0.4	4
0.4-0.5	3
0.5-0.6	0
0.6-0.7	2
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
0.6596	Remote Similarity	NPD8171	Phase 2
0.6238	Remote Similarity	NPD8170	Phase 2

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