NPASS Compound

Natural Product: NPC488942

Natural Product ID	NPC488942
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DZDCBMUKBVGLRI-DYRDHFODSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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 111117 0 0 0 0 0 0 0 0999 V2000 -4.7561 0.4012 1.9816 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8688 -0.5994 0.8780 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6843 -0.0999 -0.2996 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8494 -0.2739 -1.5343 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4974 0.4159 -1.4019 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8956 0.1170 -0.0676 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5851 -0.9710 0.4836 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5870 -0.3080 -0.2457 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6975 0.3735 0.5824 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0647 -0.5215 1.5983 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3996 -0.1671 1.7019 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 -0.5019 0.3192 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6303 -1.9759 0.0920 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4763 0.3855 -0.7291 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4246 1.4043 -1.2782 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8068 0.9122 -1.5410 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1139 -0.4005 -0.9006 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4631 -0.4160 0.4383 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0697 -1.5557 1.2399 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4402 -1.0373 1.6091 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2784 -0.7620 0.4143 C 0 0 2 0 0 0 0 0 0 0 0 0 7.3941 -1.7849 0.4011 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8971 0.6159 0.4415 C 0 0 1 0 0 0 0 0 0 0 0 0 7.8834 0.8487 1.5011 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2810 0.0835 2.4680 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3064 0.7800 3.2817 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8943 0.3180 4.2911 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4888 2.0149 2.7267 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6257 2.1413 1.6273 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4564 0.7321 -0.9543 C 0 0 2 0 0 0 0 0 0 0 0 0 6.4441 -0.0000 -1.7904 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5442 -0.7909 -0.9054 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6255 -2.1301 -1.3355 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7158 0.1593 -1.0890 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8458 0.7712 -1.5477 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7862 1.9730 -1.8955 O 0 0 0 0 0 0 0 0 0 0 0 0 11.1168 0.0183 -1.6288 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2822 1.1431 -0.1954 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6689 1.8125 -1.4828 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4231 0.2533 -2.6833 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6005 -0.7771 -3.5998 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8100 -0.9090 -0.3952 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9769 -0.2282 -0.1532 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.0048 -0.3249 -1.2495 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.1280 0.6516 -0.8819 C 0 0 2 0 0 0 0 0 0 0 0 0 -10.5902 0.4892 0.5277 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.4987 0.1439 1.5003 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.1391 -0.4650 2.7307 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.0316 0.4514 3.2693 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6132 -0.8013 0.9870 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.1392 1.7162 0.9523 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.2115 0.4910 -1.7457 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4950 0.1313 -2.4622 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0242 1.4290 1.6540 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7594 0.3922 2.4760 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4812 0.1531 2.8089 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3511 -1.5082 1.2751 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9366 0.9498 -0.0688 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7043 -1.3623 -1.6947 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8203 0.1162 -2.2154 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9741 0.9396 0.6733 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3295 1.1092 1.1637 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5324 -0.4423 2.6038 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2390 -1.5640 1.2791 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5138 0.8991 1.9156 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8290 -0.7980 2.4789 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5357 -2.5304 1.0476 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4803 -2.4908 -0.4472 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6833 -2.0898 -0.4510 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0699 -0.2612 -1.5642 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9889 1.7756 -2.2264 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4922 2.2924 -0.6159 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9333 0.7564 -2.6562 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5812 1.6410 -1.2529 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5378 -1.1438 -1.5413 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7153 0.5220 0.9851 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4821 -1.8479 2.1019 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2607 -2.4145 0.5324 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8886 -1.7910 2.3146 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2648 -0.0824 2.1858 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3111 -2.4164 -0.5420 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3969 -1.3909 0.5250 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2562 -2.5718 1.2043 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0752 1.3992 0.5181 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9903 -0.9162 2.7535 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2274 2.3817 0.7551 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9086 2.9665 1.8983 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4948 1.8079 -1.2636 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0307 -0.6518 -2.5048 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9499 0.7295 -2.4414 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5814 -2.1890 -2.3245 H 0 0 0 0 0 0 0 0 0 0 0 0 11.9934 0.6784 -1.3607 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1559 -0.8202 -0.8876 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2584 -0.4591 -2.6277 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6954 1.9833 0.4188 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2677 1.5948 -1.0756 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4156 2.1514 -2.3871 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0541 -0.4370 -4.5451 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6361 -1.3000 -3.8063 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2315 -1.5461 -3.0712 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8227 0.8723 0.0478 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4191 -1.3527 -1.3310 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6861 1.6717 -0.9960 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.4147 -0.2550 0.6100 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8861 1.0237 1.8111 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6730 -1.3962 2.3786 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3905 -0.6957 3.5072 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9258 0.0750 3.4443 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3652 2.2982 0.1746 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0196 0.1931 -1.2536 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0965 -0.0255 -3.2127 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 6 12 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 0 21 22 1 6 21 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 23 30 1 0 30 31 1 0 31 32 1 0 32 33 1 6 30 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 14 38 1 0 5 39 1 0 4 40 1 0 40 41 1 0 3 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 47 50 1 0 46 51 1 0 45 52 1 0 44 53 1 0 7 2 1 0 38 9 1 0 50 43 1 0 18 12 1 0 32 21 1 0 32 17 1 0 29 24 1 0 1 54 1 0 1 55 1 0 1 56 1 0 2 57 1 1 3 58 1 1 4 59 1 6 5 60 1 6 6 61 1 1 9 62 1 1 10 63 1 0 10 64 1 0 11 65 1 0 11 66 1 0 13 67 1 0 13 68 1 0 13 69 1 0 14 70 1 6 15 71 1 0 15 72 1 0 16 73 1 0 16 74 1 0 17 75 1 6 18 76 1 1 19 77 1 0 19 78 1 0 20 79 1 0 20 80 1 0 22 81 1 0 22 82 1 0 22 83 1 0 23 84 1 6 25 85 1 0 29 86 1 0 29 87 1 0 30 88 1 6 31 89 1 0 31 90 1 0 33 91 1 0 37 92 1 0 37 93 1 0 37 94 1 0 38 95 1 0 38 96 1 0 39 97 1 0 41 98 1 0 41 99 1 0 41100 1 0 43101 1 1 44102 1 6 45103 1 1 46104 1 6 47105 1 1 48106 1 0 48107 1 0 49108 1 0 51109 1 0 52110 1 0 53111 1 0 M END

Standard InCHIKey	DZDCBMUKBVGLRI-DYRDHFODSA-N
Standard InCHI	InChI=1S/C38H58O15/c1-17-32(53-34-30(44)29(43)28(42)25(15-39)52-34)33(47-5)31(45)35(49-17)51-21-8-10-36(3)20(13-21)6-7-23-22(36)9-11-37(4)27(19-12-26(41)48-16-19)24(50-18(2)40)14-38(23,37)46/h12,17,20-25,27-35,39,42-46H,6-11,13-16H2,1-5H3/t17-,20+,21-,22-,23+,24-,25+,27-,28+,29-,30+,31+,32-,33-,34-,35-,36-,37+,38-/m0/s1
SMILES	C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)O[C@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](C4=CC(=O)OC4)[C@H](C[C@]32O)OC(=O)C)C1)O)OC)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	754.38	Volume:	729.853 ? Van der Waals volume.
Dense:	1.034	LogP:	0.75 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.391 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.854 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	39.0
TPSA:	220.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	6.0	Rings:	7.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.147	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.783	Fsp³:	0.895
MCE-18:	136.111 ? 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:	0.716	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.015 ? 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:	0.134	Promiscuous compounds:	0.383

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.862	MDCK Permeability:	-5.251
Pgp-inhibitor:	0.209	Pgp-substrate:	0.966
PAMPA:	0.999 ? 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):	0.076
20% Bioavailability (F20%):	0.258	30% Bioavailability (F30%):	0.854
50% Bioavailability (F50%):	0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.513
Plasma Protein Binding (PPB):	59.563%	Volume Distribution (VD):	-0.62
Fu:	40.495% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.007
BSEP inhibitor:	0.834

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.232	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.6	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.025 ? 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):

1.092

Half-life (T1/2):

3.245

ADMET: Toxicity

hERG Blockers:	0.011	hERG Blockers (10um):	0.064
Human Hepatotoxicity (H-HT):	0.444	Drug-induced Liver Injury (DILI):	0.938
AMES Toxicity:	0.977	Rat Oral Acute Toxicity:	0.317
Maximum Recommended Daily Dose:	0.706	Skin Sensitization:	1.0
Carcinogencity:	0.37	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.191
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.976
Hematotoxicity:	0.949	Drug-induced Nephrotoxicity:	0.981
Genotoxicity:	0.98	RPMI-8226 Immunitoxicity:	0.597
A549 Cytotoxicity:	0.461	Hek293 Cytotoxicity:	0.707
BCF:	0.488 ? 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:	3.269 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.879 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.943 ? 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
NPO40948	Vallaris glabra	Species	n.a.	n.a.	Leaves	n.a.	n.a.	PMID[29072457]
NPO40948	Vallaris glabra	Species	n.a.	n.a.	Stems	n.a.	n.a.	PMID[31820973]

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	4

Activity Type	# Activity
Cell line	4

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
NPT81	Cell line	A549	Homo sapiens	IC50	=	100.0	nM	PMID[29072457]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	200.0	nM	PMID[29072457]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	700.0	nM	PMID[29072457]
NPT20987	Cell line	HeLa S3	Homo sapiens	IC50	=	200.0	nM	PMID[29072457]

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 NPC488942 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	16614
0.1-0.2	27809
0.2-0.3	4497
0.3-0.4	726
0.4-0.5	103
0.5-0.6	53
0.6-0.7	32
0.7-0.8	0
0.8-0.85	5
0.85-0.9	0
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC488943
0.9341	High Similarity	NPC488945
0.9341	High Similarity	NPC488946
0.8478	Intermediate Similarity	NPC488938
0.8478	Intermediate Similarity	NPC488937
0.8061	Intermediate Similarity	NPC488947
0.8022	Intermediate Similarity	NPC231518
0.8022	Intermediate Similarity	NPC488944
0.7979	Intermediate Similarity	NPC475219
0.7935	Intermediate Similarity	NPC486143
0.7935	Intermediate Similarity	NPC486142
0.7935	Intermediate Similarity	NPC486149
0.7526	Intermediate Similarity	NPC479360
0.7526	Intermediate Similarity	NPC479359
0.7449	Intermediate Similarity	NPC486144
0.7449	Intermediate Similarity	NPC486145
0.7449	Intermediate Similarity	NPC486147
0.7449	Intermediate Similarity	NPC486148
0.7263	Intermediate Similarity	NPC488941
0.7263	Intermediate Similarity	NPC488940
0.7204	Intermediate Similarity	NPC5883
0.7129	Intermediate Similarity	NPC120390
0.701	Intermediate Similarity	NPC486135
0.701	Intermediate Similarity	NPC486137
0.6979	Remote Similarity	NPC479353
0.6979	Remote Similarity	NPC479354
0.6939	Remote Similarity	NPC232785
0.6939	Remote Similarity	NPC486139
0.6869	Remote Similarity	NPC486146
0.6857	Remote Similarity	NPC474423
0.6842	Remote Similarity	NPC103534
0.6842	Remote Similarity	NPC44899
0.6842	Remote Similarity	NPC304260
0.6842	Remote Similarity	NPC29639
0.6739	Remote Similarity	NPC5311
0.6701	Remote Similarity	NPC236973
0.6667	Remote Similarity	NPC488935
0.6667	Remote Similarity	NPC488936
0.6602	Remote Similarity	NPC486136
0.6571	Remote Similarity	NPC486134
0.6571	Remote Similarity	NPC486141
0.6569	Remote Similarity	NPC479357
0.6476	Remote Similarity	NPC74259
0.6476	Remote Similarity	NPC475419
0.6429	Remote Similarity	NPC30483
0.6429	Remote Similarity	NPC470897
0.6415	Remote Similarity	NPC474908
0.64	Remote Similarity	NPC475629
0.6373	Remote Similarity	NPC488939
0.62	Remote Similarity	NPC292467
0.6139	Remote Similarity	NPC486130
0.6078	Remote Similarity	NPC486127
0.604	Remote Similarity	NPC40749
0.6	Remote Similarity	NPC99620
0.6	Remote Similarity	NPC486138
0.6	Remote Similarity	NPC276838
0.5981	Remote Similarity	NPC475590
0.5963	Remote Similarity	NPC117445
0.5963	Remote Similarity	NPC308262
0.5905	Remote Similarity	NPC329986
0.5905	Remote Similarity	NPC140092
0.5882	Remote Similarity	NPC32177
0.5882	Remote Similarity	NPC469756
0.5882	Remote Similarity	NPC275901
0.5876	Remote Similarity	NPC77299
0.5876	Remote Similarity	NPC480906
0.5825	Remote Similarity	NPC188234
0.5816	Remote Similarity	NPC480914
0.5794	Remote Similarity	NPC486132
0.5794	Remote Similarity	NPC486131
0.5766	Remote Similarity	NPC486150
0.5741	Remote Similarity	NPC486128
0.5714	Remote Similarity	NPC208193
0.5688	Remote Similarity	NPC479358
0.5676	Remote Similarity	NPC486140
0.5673	Remote Similarity	NPC480910
0.5673	Remote Similarity	NPC240070
0.5673	Remote Similarity	NPC480909
0.5652	Remote Similarity	NPC119855
0.5588	Remote Similarity	NPC480907
0.5556	Remote Similarity	NPC479356
0.5556	Remote Similarity	NPC479355
0.55	Remote Similarity	NPC199428
0.55	Remote Similarity	NPC109448
0.55	Remote Similarity	NPC76572
0.55	Remote Similarity	NPC310341
0.55	Remote Similarity	NPC193382
0.549	Remote Similarity	NPC193893
0.5487	Remote Similarity	NPC486133
0.5437	Remote Similarity	NPC72260
0.5421	Remote Similarity	NPC125077
0.5385	Remote Similarity	NPC486152
0.5354	Remote Similarity	NPC471633
0.5321	Remote Similarity	NPC146857
0.53	Remote Similarity	NPC84987
0.5248	Remote Similarity	NPC469750
0.5248	Remote Similarity	NPC99080
0.5243	Remote Similarity	NPC93883
0.5234	Remote Similarity	NPC32793
0.5234	Remote Similarity	NPC116075
0.5196	Remote Similarity	NPC84949
0.5196	Remote Similarity	NPC480562
0.5196	Remote Similarity	NPC74945
0.5196	Remote Similarity	NPC31354
0.5196	Remote Similarity	NPC69576
0.5138	Remote Similarity	NPC55532
0.513	Remote Similarity	NPC329675
0.513	Remote Similarity	NPC194716
0.5096	Remote Similarity	NPC471353

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488942 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6460
0.1-0.2	2584
0.2-0.3	87
0.3-0.4	5
0.4-0.5	11
0.5-0.6	2
0.6-0.7	0
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	Drug ID	Developmental Stage
0.8022	Intermediate Similarity	NPD8033	Approved
0.5437	Remote Similarity	NPD8294	Phase 4
0.5138	Remote Similarity	NPD8377	Phase 4

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