NPASS Compound

Natural Product: NPC470486

Natural Product ID	NPC470486
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ilicifoliunine A
IUPAC Name	n.a.
Synonyms	Ilicifoliunine A
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2047340
PubChem CID	70684078
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 106111 0 0 0 0 0 0 0 0999 V2000 -5.2815 -3.6704 -0.2683 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2805 -3.0825 -1.1956 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4551 -3.1945 -2.4284 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1896 -2.4309 -0.6487 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2246 -1.8643 -1.5717 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1706 -1.2320 -0.7058 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5561 -2.2756 0.1907 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0328 -3.5684 -0.0079 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7858 -4.3264 0.8278 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0667 -3.7701 1.8941 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2581 -5.7025 0.5418 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9138 -2.1681 0.4246 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2394 -3.2211 1.2683 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6481 -3.1775 2.5587 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7503 -2.0522 3.0713 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9566 -4.4428 3.3123 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7975 -1.9802 -0.7653 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0258 -1.3641 -1.9058 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0861 -0.4750 -1.4461 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5202 0.4673 -0.5679 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1260 1.7211 -0.8183 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1384 1.5305 -1.6239 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2275 1.0425 -0.7465 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9495 -0.1827 0.0689 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2288 -0.6552 0.4639 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5375 -0.8158 1.7998 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6948 -0.5443 2.6938 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8542 -1.3088 2.2773 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7536 2.0217 0.1293 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0471 2.4880 0.0950 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8098 2.0017 -0.7827 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5491 3.4991 1.0167 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7483 4.0540 1.9857 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2331 5.0211 2.8658 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5530 5.4273 2.7550 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3597 4.8753 1.7867 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8563 3.9188 0.9267 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7019 0.3454 -2.5065 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1708 0.7420 -3.5144 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2239 2.5700 0.4139 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0945 2.6633 -1.5048 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3038 2.6429 -0.7783 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4265 3.3590 -1.0698 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4323 4.1384 -2.0693 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6538 3.3005 -0.3087 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2603 2.0885 -0.0479 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6627 0.8234 -0.5320 C 0 0 2 0 0 0 0 0 0 0 0 0 5.0953 -0.4129 0.2300 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2197 -1.5051 -0.3608 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6103 -2.5574 -0.8347 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8777 -1.2005 -0.3190 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5409 -0.7421 0.0788 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9579 0.6453 -2.0291 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4011 2.0864 0.6539 N 0 0 0 0 0 0 0 0 0 0 0 0 6.9550 3.2460 1.1023 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3513 4.4499 0.8424 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1885 4.4850 0.1299 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6343 -2.4409 -2.8910 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9019 -0.5655 -2.6378 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7385 -4.5756 -0.7023 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8023 -3.9468 0.6917 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1077 -2.9648 -0.0567 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8898 -1.1279 -2.0956 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9090 -2.5887 -2.2987 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9906 -2.0576 1.2231 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3847 -6.3845 0.6485 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6437 -5.8094 -0.4904 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9884 -5.9831 1.3105 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0601 -1.2419 1.0396 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4061 -5.1283 2.5448 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6306 -4.2637 4.1607 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0168 -4.8587 3.6908 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2487 -2.9162 -1.1448 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4511 2.3883 -2.1969 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0948 0.7765 -1.4242 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3845 -0.0507 0.9870 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1522 -0.6647 3.1419 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7377 -2.3611 2.5890 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5892 -1.1696 1.4694 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7209 3.7598 2.0961 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6153 5.4512 3.6157 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9659 6.1835 3.4285 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3931 5.2227 1.7330 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5358 3.5098 0.1739 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5741 -0.0305 -3.0244 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2934 1.4687 -4.0178 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8776 3.3931 0.0060 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5856 2.0591 1.2692 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6845 3.1471 0.7757 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7185 3.7043 -1.4644 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3351 2.4580 -2.5328 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5680 0.9493 -0.4451 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8705 -0.2504 1.2977 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0982 -0.1908 0.8846 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9538 -0.5439 -0.9155 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6706 -1.8235 0.3426 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6225 -0.3824 -2.2782 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0446 0.7736 -2.2235 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3418 1.4039 -2.5553 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8760 3.2527 1.6696 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7833 5.3676 1.1940 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6553 5.4228 -0.1187 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0613 -2.1565 -3.6621 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5717 -2.7647 -3.4532 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3228 -3.3434 -2.3601 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1454 0.1628 -2.0413 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 6 5 1 6 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 7 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 12 17 1 0 17 18 1 0 18 19 1 0 19 20 1 1 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 23 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 22 38 1 0 38 39 1 0 21 40 1 1 21 41 1 0 41 42 1 0 42 43 1 0 43 44 2 0 43 45 1 0 45 46 2 0 46 47 1 0 47 48 1 0 48 49 1 0 49 50 2 0 49 51 1 0 48 52 1 0 47 53 1 0 46 54 1 0 54 55 2 0 55 56 1 0 56 57 2 0 18 58 1 0 18 59 1 6 24 6 1 0 37 32 1 0 57 45 1 0 19 6 1 0 51 17 1 0 38 19 1 0 1 60 1 0 1 61 1 0 1 62 1 0 5 63 1 0 5 64 1 0 7 65 1 1 11 66 1 0 11 67 1 0 11 68 1 0 12 69 1 1 16 70 1 0 16 71 1 0 16 72 1 0 17 73 1 6 22 74 1 6 23 75 1 6 24 76 1 1 28 77 1 0 28 78 1 0 28 79 1 0 33 80 1 0 34 81 1 0 35 82 1 0 36 83 1 0 37 84 1 0 38 85 1 6 39 86 1 0 40 87 1 0 40 88 1 0 40 89 1 0 41 90 1 0 41 91 1 0 47 92 1 6 48 93 1 1 52 94 1 0 52 95 1 0 52 96 1 0 53 97 1 0 53 98 1 0 53 99 1 0 55100 1 0 56101 1 0 57102 1 0 58103 1 0 58104 1 0 58105 1 0 59106 1 0 M END

Standard InCHIKey	CFVLRNWLPYMNOZ-ZFMWWAAGSA-N
Standard InCHI	InChI=1S/C41H47NO17/c1-19-20(2)35(48)58-32-30(54-22(4)44)34(56-24(6)46)40(18-52-21(3)43)33(55-23(5)45)29(57-36(49)25-13-10-9-11-14-25)27-31(47)41(40,39(32,8)51)59-38(27,7)17-53-37(50)26-15-12-16-42-28(19)26/h9-16,19-20,27,29-34,47,51H,17-18H2,1-8H3/t19-,20-,27+,29-,30-,31+,32-,33+,34-,38-,39-,40+,41-/m0/s1
SMILES	CC(=O)OC[C@]12[C@@H](OC(=O)C)[C@@H](OC(=O)C)[C@H]3[C@]([C@@]42O[C@@]([C@H]([C@@H]([C@H]1OC(=O)C)OC(=O)c1ccccc1)[C@H]4O)(C)COC(=O)c1c([C@H]([C@@H](C(=O)O3)C)C)nccc1)(C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	825.28	Volume:	792.51 ? Van der Waals volume.
Dense:	1.041	LogP:	1.272 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.697 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.267 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	42.0
TPSA:	246.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	18.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.298	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.522	Fsp³:	0.561
MCE-18:	217.438 ? 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:	0.672	Fluc inhibitor:	0.01 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.014 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.318 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.009	Promiscuous compounds:	0.143

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.69	MDCK Permeability:	-5.058
Pgp-inhibitor:	0.883	Pgp-substrate:	0.491
PAMPA:	0.94 ? 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%):	0.013	30% Bioavailability (F30%):	0.467
50% Bioavailability (F50%):	0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	1.0
Plasma Protein Binding (PPB):	55.557%	Volume Distribution (VD):	-0.248
Fu:	43.388% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.0
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.004
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:	0.011	CYP3A4-substrate:	0.015
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.964 ? 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):

0.464

Half-life (T1/2):

1.692

ADMET: Toxicity

hERG Blockers:	0.003	hERG Blockers (10um):	0.096
Human Hepatotoxicity (H-HT):	0.275	Drug-induced Liver Injury (DILI):	0.981
AMES Toxicity:	0.954	Rat Oral Acute Toxicity:	0.22
Maximum Recommended Daily Dose:	0.524	Skin Sensitization:	1.0
Carcinogencity:	0.69	Eye Corrosion:	0.0
Eye Irritation:	0.354	Respiratory Toxicity:	0.269
Drug-induced Neurotoxicity:	0.339	Ototoxicity:	0.673
Hematotoxicity:	0.791	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	0.963	RPMI-8226 Immunitoxicity:	0.445
A549 Cytotoxicity:	0.189	Hek293 Cytotoxicity:	0.143
BCF:	0.565 ? 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:	3.399 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.837 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.398 ? 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
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15043435]
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	root bark	n.a.	n.a.	PMID[17555350]
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22559947]
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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	3
Ratio IC50	1

Activity Type	# Activity
Organism	3
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
NPT634	Organism	Leishmania amazonensis	Leishmania amazonensis	IC50	>	100000.0	nM	PMID[23376010]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	27700.0	nM	PMID[23376010]
NPT1219	Organism	Leishmania chagasi	Leishmania chagasi	IC50	>	100000.0	nM	PMID[23376010]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	46.2	n.a.	PMID[19128055]

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 NPC470486 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	19564
0.1-0.2	28841
0.2-0.3	1177
0.3-0.4	193
0.4-0.5	28
0.5-0.6	27
0.6-0.7	18
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.914	High Similarity	NPC471977
0.8681	High Similarity	NPC475137
0.8081	Intermediate Similarity	NPC471190
0.78	Intermediate Similarity	NPC87152
0.7624	Intermediate Similarity	NPC475631
0.7379	Intermediate Similarity	NPC475596
0.7379	Intermediate Similarity	NPC476110
0.7282	Intermediate Similarity	NPC475600
0.7184	Intermediate Similarity	NPC475303
0.7009	Intermediate Similarity	NPC237702
0.69	Remote Similarity	NPC473850
0.6832	Remote Similarity	NPC76565
0.6832	Remote Similarity	NPC601313
0.6822	Remote Similarity	NPC30456
0.6822	Remote Similarity	NPC475644
0.6822	Remote Similarity	NPC488904
0.6818	Remote Similarity	NPC327769
0.6569	Remote Similarity	NPC35208
0.6542	Remote Similarity	NPC475301
0.6296	Remote Similarity	NPC326930
0.6283	Remote Similarity	NPC328928
0.6271	Remote Similarity	NPC483854
0.6218	Remote Similarity	NPC482915
0.6167	Remote Similarity	NPC483855
0.6095	Remote Similarity	NPC475408
0.6091	Remote Similarity	NPC328186
0.6053	Remote Similarity	NPC319880
0.6053	Remote Similarity	NPC320324
0.5926	Remote Similarity	NPC475498
0.5913	Remote Similarity	NPC477787
0.5893	Remote Similarity	NPC316841
0.5872	Remote Similarity	NPC473833
0.5862	Remote Similarity	NPC327904
0.5812	Remote Similarity	NPC483853
0.5812	Remote Similarity	NPC608314
0.5804	Remote Similarity	NPC122968
0.5804	Remote Similarity	NPC228377
0.5726	Remote Similarity	NPC38959
0.5714	Remote Similarity	NPC475426
0.569	Remote Similarity	NPC601643
0.5556	Remote Similarity	NPC244839
0.5484	Remote Similarity	NPC483856
0.547	Remote Similarity	NPC473689
0.547	Remote Similarity	NPC292416
0.5424	Remote Similarity	NPC253482
0.5424	Remote Similarity	NPC600546
0.5398	Remote Similarity	NPC473506
0.5364	Remote Similarity	NPC250807
0.5364	Remote Similarity	NPC57797
0.5345	Remote Similarity	NPC477788
0.5294	Remote Similarity	NPC475406
0.5167	Remote Similarity	NPC475648
0.5083	Remote Similarity	NPC483893
0.5043	Remote Similarity	NPC146824
0.5041	Remote Similarity	NPC600583

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470486 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4104
0.1-0.2	5000
0.2-0.3	44
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