NPASS Compound

Natural Product: NPC477788

Natural Product ID	NPC477788
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Oppositine B
IUPAC Name	[(1S,3S,18R,19S,20R,21R,22S,23R,24R,25R,26R)-19,22,23,25-tetraacetyloxy-21-(acetyloxymethyl)-13-ethyl-3,26-dimethyl-6,16-dioxo-2,5,17-trioxa-11-azapentacyclo[16.7.1.01,21.03,24.07,12]hexacosa-7(12),8,10-trien-20-yl] benzoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44566464
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 113118 0 0 0 0 0 0 0 0999 V2000 7.7496 0.8839 -2.1789 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7174 -0.2424 -2.3645 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8934 -0.3928 -1.1653 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0859 0.7828 -0.7087 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7936 0.8958 -1.4693 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7565 1.7138 -0.7822 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6911 2.9449 -0.8557 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7671 1.0734 0.0094 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7284 1.7807 0.6715 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0950 0.9753 1.8107 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4239 -0.2657 1.1629 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7994 -1.4348 2.0124 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2951 -2.5463 1.0370 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8892 -2.4774 -0.2984 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6217 -1.2610 -0.7409 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5209 -0.0521 0.1814 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4839 1.2717 -0.5324 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2662 2.1183 -0.3934 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6872 3.4728 -0.3539 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3904 4.3238 -1.3975 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2616 3.9285 -2.4271 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7813 5.7697 -1.4514 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6774 2.0208 -0.5058 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5090 2.3848 -1.4998 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2271 2.0260 -2.6422 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6912 3.1680 -1.2613 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0161 3.5392 0.0232 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1416 4.2934 0.2759 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9909 4.7062 -0.7592 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6525 4.3260 -2.0539 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5088 3.5650 -2.2734 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8871 0.0066 0.8767 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9256 0.1535 -0.1106 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2402 0.1727 0.3559 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4202 0.0659 1.5935 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3558 0.3117 -0.5875 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9262 -1.5176 -1.1814 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4255 -1.3957 -2.4397 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5888 -0.9995 -3.2882 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8104 -1.6785 -2.8788 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7126 -3.6578 -0.4184 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4517 -4.7157 -1.2358 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4072 -4.6614 -1.9452 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3366 -5.9195 -1.3276 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1264 -1.9664 0.9631 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7634 -0.7026 0.5895 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9699 -2.4294 -0.1843 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3505 -2.5032 0.0562 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1624 -1.6713 0.7275 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7346 -0.6899 1.3254 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6004 -1.7760 0.8459 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4808 -1.1797 -0.0784 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7729 -1.3465 0.1511 N 0 0 0 0 0 0 0 0 0 0 0 0 8.2808 -2.0337 1.1909 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4034 -2.6239 2.1106 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0557 -2.4715 1.9036 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7729 -2.3507 2.2007 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1612 -1.4221 3.2283 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7421 -1.6802 4.4493 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9723 -1.9529 4.4592 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0089 -1.6492 5.7337 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8063 1.7588 2.6673 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3398 1.8455 -2.5443 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0365 1.0096 -1.1275 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6678 0.6943 -2.7602 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1570 0.0040 -3.2866 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3281 -1.1676 -2.5452 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0460 -1.1614 -1.5433 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7110 1.6809 -1.1719 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1082 1.0649 0.3214 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9303 1.3782 -2.4879 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4269 -0.1233 -1.7261 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2362 2.6273 1.1518 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9544 0.6688 2.4454 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8254 -1.6900 2.1613 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3122 -3.5264 1.5072 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0604 -2.7143 -1.0302 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1257 -0.9110 -1.6731 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4983 0.9885 -1.6416 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3038 2.0574 -1.3751 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0999 6.3481 -1.8325 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6098 5.9380 -2.1755 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0648 6.1183 -0.4461 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4102 3.2596 0.8800 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4242 4.5997 1.2691 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8813 5.2995 -0.5823 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2944 4.6389 -2.8494 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3206 3.3140 -3.3273 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1246 -0.6766 1.6320 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9453 1.0381 1.3635 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7787 -0.7251 -0.7581 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1880 0.9360 -0.1632 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0584 0.6555 -1.5889 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3962 -2.1877 -2.0653 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7225 -2.4271 -3.7194 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3331 -0.8210 -3.3126 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1215 -5.7784 -2.0766 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7237 -6.1378 -0.3001 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6701 -6.7785 -1.5744 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7021 -3.5040 -0.4702 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8709 -1.7909 -1.1095 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3400 -2.1253 1.3067 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7638 -3.1860 2.9618 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2867 -2.8888 2.6229 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0262 -1.6552 2.9777 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1521 -3.1555 2.7649 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7008 -3.0065 2.0451 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0906 -1.5390 5.5661 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3796 -0.7579 6.3053 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2755 -2.5405 6.3302 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2256 2.2973 3.4825 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2601 2.5858 2.0868 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5282 1.1612 3.2608 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 2 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 2 0 20 22 1 0 17 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 16 32 1 1 32 33 1 0 33 34 1 0 34 35 2 0 34 36 1 0 15 37 1 0 37 38 1 0 38 39 2 0 38 40 1 0 14 41 1 0 41 42 1 0 42 43 2 0 42 44 1 0 13 45 1 0 45 46 1 0 45 47 1 0 47 48 1 0 48 49 1 0 49 50 2 0 49 51 1 0 51 52 2 0 52 53 1 0 53 54 2 0 54 55 1 0 55 56 2 0 45 57 1 1 12 58 1 0 58 59 1 0 59 60 2 0 59 61 1 0 10 62 1 0 52 3 1 0 18 9 1 0 16 11 1 0 11 46 1 6 31 26 1 0 56 51 1 0 1 63 1 0 1 64 1 0 1 65 1 0 2 66 1 0 2 67 1 0 3 68 1 0 4 69 1 0 4 70 1 0 5 71 1 0 5 72 1 0 9 73 1 1 10 74 1 1 12 75 1 1 13 76 1 1 14 77 1 6 15 78 1 6 17 79 1 6 18 80 1 6 22 81 1 0 22 82 1 0 22 83 1 0 27 84 1 0 28 85 1 0 29 86 1 0 30 87 1 0 31 88 1 0 32 89 1 0 32 90 1 0 36 91 1 0 36 92 1 0 36 93 1 0 40 94 1 0 40 95 1 0 40 96 1 0 44 97 1 0 44 98 1 0 44 99 1 0 47100 1 0 47101 1 0 54102 1 0 55103 1 0 56104 1 0 57105 1 0 57106 1 0 57107 1 0 61108 1 0 61109 1 0 61110 1 0 62111 1 0 62112 1 0 62113 1 0 M END

Standard InCHIKey	PWFIPRRXNKFZDH-KILMRAKKSA-N
Standard InCHI	InChI=1S/C44H51NO17/c1-9-28-17-18-31(51)60-34-22(2)44-37(58-26(6)49)32(42(8,62-44)20-55-41(53)30-16-13-19-45-33(28)30)35(56-24(4)47)38(59-27(7)50)43(44,21-54-23(3)46)39(36(34)57-25(5)48)61-40(52)29-14-11-10-12-15-29/h10-16,19,22,28,32,34-39H,9,17-18,20-21H2,1-8H3/t22-,28?,32-,34-,35-,36+,37-,38-,39+,42-,43-,44-/m1/s1
SMILES	CCC1CCC(=O)O[C@@H]2[C@H]([C@@]34[C@@H]([C@@H]([C@H]([C@H]([C@@]3([C@H]([C@H]2OC(=O)C)OC(=O)C5=CC=CC=C5)COC(=O)C)OC(=O)C)OC(=O)C)[C@](O4)(COC(=O)C6=C1N=CC=C6)C)OC(=O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	865.32	Volume:	841.761 ? Van der Waals volume.
Dense:	1.028	LogP:	1.711 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.13 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.645 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	44.0
TPSA:	232.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	18.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.258	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.603	Fsp³:	0.568
MCE-18:	208.435 ? 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:	0.678	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.157 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.024	Promiscuous compounds:	0.066

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.152	MDCK Permeability:	-4.788
Pgp-inhibitor:	0.999	Pgp-substrate:	0.016
PAMPA:	0.068 ? 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%):	0.002	30% Bioavailability (F30%):	0.117
50% Bioavailability (F50%):	0.903

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.305	MRP1:	1.0
Plasma Protein Binding (PPB):	80.226%	Volume Distribution (VD):	-0.529
Fu:	18.705% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.986	BCRP inhibitor:	0.0
BSEP inhibitor:	0.97

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:	0.0
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.991
HLM stability:	0.956 ? 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):

1.296

Half-life (T1/2):

1.145

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.092
Human Hepatotoxicity (H-HT):	0.325	Drug-induced Liver Injury (DILI):	0.994
AMES Toxicity:	0.966	Rat Oral Acute Toxicity:	0.237
Maximum Recommended Daily Dose:	0.508	Skin Sensitization:	1.0
Carcinogencity:	0.933	Eye Corrosion:	0.0
Eye Irritation:	0.034	Respiratory Toxicity:	0.008
Drug-induced Neurotoxicity:	0.623	Ototoxicity:	0.349
Hematotoxicity:	0.73	Drug-induced Nephrotoxicity:	0.991
Genotoxicity:	0.968	RPMI-8226 Immunitoxicity:	0.388
A549 Cytotoxicity:	0.591	Hek293 Cytotoxicity:	0.507
BCF:	0.519 ? 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:	3.406 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.655 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.329 ? 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
NPO6692	Pleurostylia opposita	Species	Celastraceae	Eukaryota	Stem bark	University of Colombo Campus, Sri Lanka	2005-JUL	PMID[17190474]
NPO6692	Pleurostylia opposita	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6692	Pleurostylia opposita	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
EC50	1

Activity Type	# Activity
Others	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
NPT2	Others	Unspecified	n.a.	EC50	=	26000	nM	PMID[17190474]

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 NPC477788 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	22823
0.1-0.2	25660
0.2-0.3	1071
0.3-0.4	203
0.4-0.5	63
0.5-0.6	32
0.6-0.7	5
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	Natural Product ID
0.7941	Intermediate Similarity	NPC477787
0.6422	Remote Similarity	NPC476110
0.6273	Remote Similarity	NPC475596
0.6239	Remote Similarity	NPC475303
0.6036	Remote Similarity	NPC475600
0.6036	Remote Similarity	NPC475631
0.5893	Remote Similarity	NPC87152
0.5893	Remote Similarity	NPC316841
0.5862	Remote Similarity	NPC327904
0.5789	Remote Similarity	NPC475644
0.5739	Remote Similarity	NPC483893
0.569	Remote Similarity	NPC475406
0.5678	Remote Similarity	NPC327769
0.5664	Remote Similarity	NPC122968
0.5664	Remote Similarity	NPC328186
0.5664	Remote Similarity	NPC228377
0.5652	Remote Similarity	NPC30456
0.5652	Remote Similarity	NPC488904
0.5641	Remote Similarity	NPC319880
0.5641	Remote Similarity	NPC320324
0.5565	Remote Similarity	NPC483895
0.5565	Remote Similarity	NPC482915
0.547	Remote Similarity	NPC473689
0.547	Remote Similarity	NPC483894
0.547	Remote Similarity	NPC292416
0.5462	Remote Similarity	NPC38959
0.5455	Remote Similarity	NPC76565
0.5455	Remote Similarity	NPC601313
0.5424	Remote Similarity	NPC244839
0.536	Remote Similarity	NPC483854
0.5345	Remote Similarity	NPC470486
0.5345	Remote Similarity	NPC471977
0.5172	Remote Similarity	NPC326930
0.5169	Remote Similarity	NPC471190
0.5128	Remote Similarity	NPC475301
0.5089	Remote Similarity	NPC250807
0.5089	Remote Similarity	NPC57797
0.5088	Remote Similarity	NPC475498

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477788 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4168
0.1-0.2	4936
0.2-0.3	45
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