NPASS Compound

Natural Product: NPC488937

Natural Product ID	NPC488937
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ITTDSSGXJVRXHK-JSHNNVSESA-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 116122 0 0 0 0 0 0 0 0999 V2000 -5.4169 -2.2018 1.1429 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4804 -1.1681 0.5526 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2866 0.1086 0.3746 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3856 1.2300 -0.0331 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1927 1.2701 0.8735 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5028 -0.0728 1.0343 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4411 -1.0125 1.4521 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9277 -0.3766 -0.1664 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5906 -0.5648 -0.1798 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1376 -1.9476 -0.5665 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3399 -2.0164 -0.2505 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1568 -0.9838 -0.9714 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3360 -1.4299 -2.4219 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5817 0.3895 -0.9796 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0119 1.1222 0.2589 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5019 1.3853 0.1837 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2423 0.2747 -0.5641 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5298 -0.9982 -0.2837 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3091 -2.1219 -0.8969 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6432 -2.1761 -0.1938 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4696 -0.9263 -0.3581 C 0 0 2 0 0 0 0 0 0 0 0 0 7.1615 -0.8836 -1.6991 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4615 -0.8955 0.7891 C 0 0 1 0 0 0 0 0 0 0 0 0 8.7666 -1.4740 0.5067 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9769 -0.9557 0.6199 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0018 -1.9055 0.2250 C 0 0 0 0 0 0 0 0 0 0 0 0 12.2607 -1.7116 0.2200 O 0 0 0 0 0 0 0 0 0 0 0 0 10.3587 -3.0611 -0.1453 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9848 -2.8678 -0.0080 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4479 0.5134 1.2764 C 0 0 2 0 0 0 0 0 0 0 0 0 5.9140 0.7543 1.2408 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6646 0.3305 -0.2002 C 0 0 2 0 0 0 0 0 0 0 0 0 6.2700 1.3270 -1.0014 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9415 1.4661 0.3573 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7666 2.5064 0.6785 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1238 2.6411 1.8760 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2013 3.4282 -0.4072 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0858 0.4076 -1.0826 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4384 1.8944 2.0949 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8038 3.0706 2.4349 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0001 3.5592 1.6057 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0033 3.8013 3.7133 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0749 2.4339 0.1611 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1303 3.2122 -0.9700 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2581 -0.1909 -0.5637 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5607 -0.1700 -0.1084 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.2793 0.9163 -0.9060 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.7178 0.6088 -1.1604 C 0 0 2 0 0 0 0 0 0 0 0 0 -10.2644 -0.1255 0.0473 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.4234 -1.3387 0.3797 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.2778 -2.5559 0.0814 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.4306 -2.4435 0.8564 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2375 -1.3585 -0.3535 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.3280 0.7908 1.1075 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.9459 -0.0581 -2.3387 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1252 2.1085 -0.1637 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9541 -2.7315 0.3046 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1499 -1.7746 1.8572 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7838 -2.9700 1.6801 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1408 -1.5830 -0.4232 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7785 0.3106 1.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0057 1.1305 -1.0698 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4307 1.9052 0.3250 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7764 -0.0073 1.8858 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2002 -0.4085 0.8653 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2761 -2.2106 -1.6125 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6198 -2.7376 0.0449 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4126 -1.7567 0.8468 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7670 -3.0125 -0.4636 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3798 -1.2725 -2.9496 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5547 -2.5115 -2.4977 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0873 -0.8027 -2.9388 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9614 0.9121 -1.9063 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7627 0.5033 1.1351 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5188 2.1027 0.3993 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7626 2.3814 -0.1934 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8608 1.3108 1.2514 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1632 0.4611 -1.6757 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4168 -1.1603 0.7979 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4725 -2.0200 -1.9676 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7916 -3.0791 -0.6239 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5223 -2.4268 0.8841 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1982 -3.0144 -0.6573 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2417 -0.7374 -1.6465 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7661 -0.0379 -2.3218 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9119 -1.7987 -2.2759 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0236 -1.4966 1.6568 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1788 0.0389 0.9632 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5194 -3.6232 0.6733 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5291 -3.0256 -1.0088 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8113 0.6620 2.3084 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4437 0.1069 1.9760 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8043 1.8422 1.3997 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6862 1.6097 -1.7224 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4250 3.5498 -1.1835 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1266 3.0776 -0.9136 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4324 4.4538 -0.0198 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1685 0.1908 -2.1555 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2618 1.4644 -0.9241 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0402 4.2478 4.0831 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6727 4.6846 3.5570 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4060 3.1551 4.5175 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6605 2.6182 -1.7568 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7937 4.0773 -0.7408 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1213 3.5192 -1.3106 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6776 0.0791 0.9461 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7494 1.0897 -1.8664 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2753 1.5816 -1.1941 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3120 -0.4009 -0.1860 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1780 -1.3383 1.4444 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7869 -3.5068 0.3625 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6145 -2.5662 -0.9804 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0709 -3.1746 0.7017 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7455 0.3113 1.8709 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8547 -0.4522 -2.3576 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8753 2.7022 -0.4147 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 39 40 1 0 40 41 2 0 40 42 1 0 4 43 1 0 43 44 1 0 3 45 1 0 45 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 49 50 1 0 50 51 1 0 51 52 1 0 50 53 1 0 49 54 1 0 48 55 1 0 47 56 1 0 7 2 1 0 38 9 1 0 53 46 1 0 18 12 1 0 32 21 1 0 32 17 1 0 29 24 1 0 1 57 1 0 1 58 1 0 1 59 1 0 2 60 1 6 3 61 1 1 4 62 1 6 5 63 1 6 6 64 1 1 9 65 1 1 10 66 1 0 10 67 1 0 11 68 1 0 11 69 1 0 13 70 1 0 13 71 1 0 13 72 1 0 14 73 1 6 15 74 1 0 15 75 1 0 16 76 1 0 16 77 1 0 17 78 1 6 18 79 1 1 19 80 1 0 19 81 1 0 20 82 1 0 20 83 1 0 22 84 1 0 22 85 1 0 22 86 1 0 23 87 1 1 25 88 1 0 29 89 1 0 29 90 1 0 30 91 1 1 31 92 1 0 31 93 1 0 33 94 1 0 37 95 1 0 37 96 1 0 37 97 1 0 38 98 1 0 38 99 1 0 42100 1 0 42101 1 0 42102 1 0 44103 1 0 44104 1 0 44105 1 0 46106 1 1 47107 1 6 48108 1 6 49109 1 6 50110 1 1 51111 1 0 51112 1 0 52113 1 0 54114 1 0 55115 1 0 56116 1 0 M END

Standard InCHIKey	ITTDSSGXJVRXHK-JSHNNVSESA-N
Standard InCHI	InChI=1S/C40H60O16/c1-18-33(56-36-32(47)31(46)30(45)27(16-41)55-36)34(49-6)35(53-20(3)43)37(51-18)54-23-9-11-38(4)22(14-23)7-8-25-24(38)10-12-39(5)29(21-13-28(44)50-17-21)26(52-19(2)42)15-40(25,39)48/h13,18,22-27,29-37,41,45-48H,7-12,14-17H2,1-6H3/t18-,22+,23-,24-,25+,26-,27+,29-,30+,31-,32+,33-,34+,35+,36-,37-,38-,39+,40-/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)OC(=O)C)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:	796.39	Volume:	770.598 ? Van der Waals volume.
Dense:	1.033	LogP:	0.965 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.695 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.26 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	40.0
TPSA:	226.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	16.0
H-Bond Donor:	5.0	Rings:	7.0
Heavy Atoms:	16.0

MedChem Properties

QED Drug-Likeness Score:	0.125	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.851	Fsp³:	0.875
MCE-18:	137.333 ? 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:	0.794	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? 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:	0.143	Promiscuous compounds:	0.499

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.573	MDCK Permeability:	-5.157
Pgp-inhibitor:	0.705	Pgp-substrate:	0.985
PAMPA:	0.982 ? 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):	0.827
20% Bioavailability (F20%):	0.929	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.738
Plasma Protein Binding (PPB):	56.803%	Volume Distribution (VD):	-0.591
Fu:	42.611% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.013
BSEP inhibitor:	0.444

ADMET: Metabolism

CYP1A2-inhibitor:	0.073	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.048	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.436	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.095
HLM stability:	0.0 ? 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):

1.383

Half-life (T1/2):

3.264

ADMET: Toxicity

hERG Blockers:	0.011	hERG Blockers (10um):	0.11
Human Hepatotoxicity (H-HT):	0.526	Drug-induced Liver Injury (DILI):	0.983
AMES Toxicity:	0.971	Rat Oral Acute Toxicity:	0.281
Maximum Recommended Daily Dose:	0.735	Skin Sensitization:	1.0
Carcinogencity:	0.462	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.181
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.958
Hematotoxicity:	0.923	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	0.986	RPMI-8226 Immunitoxicity:	0.494
A549 Cytotoxicity:	0.203	Hek293 Cytotoxicity:	0.556
BCF:	0.441 ? 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:	3.323 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.025 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.057 ? 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	=	1500.0	nM	PMID[29072457]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	1900.0	nM	PMID[29072457]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	5800.0	nM	PMID[29072457]
NPT20987	Cell line	HeLa S3	Homo sapiens	IC50	=	1400.0	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 NPC488937 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	16665
0.1-0.2	27817
0.2-0.3	4387
0.3-0.4	786
0.4-0.5	103
0.5-0.6	54
0.6-0.7	29
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC488938
0.9239	High Similarity	NPC488947
0.8478	Intermediate Similarity	NPC488943
0.8478	Intermediate Similarity	NPC488942
0.8152	Intermediate Similarity	NPC486146
0.7959	Intermediate Similarity	NPC488945
0.7959	Intermediate Similarity	NPC488946
0.7789	Intermediate Similarity	NPC475219
0.7576	Intermediate Similarity	NPC486134
0.7576	Intermediate Similarity	NPC486141
0.7396	Intermediate Similarity	NPC488939
0.7204	Intermediate Similarity	NPC488935
0.7204	Intermediate Similarity	NPC488936
0.7143	Intermediate Similarity	NPC486138
0.7143	Intermediate Similarity	NPC276838
0.6842	Remote Similarity	NPC103534
0.6842	Remote Similarity	NPC44899
0.6842	Remote Similarity	NPC304260
0.6842	Remote Similarity	NPC29639
0.6735	Remote Similarity	NPC231518
0.6735	Remote Similarity	NPC488944
0.6667	Remote Similarity	NPC486143
0.6667	Remote Similarity	NPC5883
0.6667	Remote Similarity	NPC486142
0.6667	Remote Similarity	NPC486149
0.6667	Remote Similarity	NPC486150
0.6602	Remote Similarity	NPC479358
0.6559	Remote Similarity	NPC5311
0.6364	Remote Similarity	NPC292467
0.6346	Remote Similarity	NPC479360
0.6346	Remote Similarity	NPC479359
0.6286	Remote Similarity	NPC486144
0.6286	Remote Similarity	NPC486145
0.6286	Remote Similarity	NPC486147
0.6286	Remote Similarity	NPC486148
0.62	Remote Similarity	NPC236973
0.6168	Remote Similarity	NPC120390
0.6168	Remote Similarity	NPC74259
0.6168	Remote Similarity	NPC475419
0.6111	Remote Similarity	NPC474908
0.61	Remote Similarity	NPC30483
0.61	Remote Similarity	NPC470897
0.6078	Remote Similarity	NPC488941
0.6078	Remote Similarity	NPC488940
0.5946	Remote Similarity	NPC474423
0.5865	Remote Similarity	NPC486135
0.5865	Remote Similarity	NPC486137
0.5833	Remote Similarity	NPC99620
0.5825	Remote Similarity	NPC479353
0.5825	Remote Similarity	NPC479354
0.581	Remote Similarity	NPC232785
0.581	Remote Similarity	NPC486139
0.5755	Remote Similarity	NPC329986
0.5755	Remote Similarity	NPC140092
0.5714	Remote Similarity	NPC77299
0.5714	Remote Similarity	NPC480906
0.57	Remote Similarity	NPC93883
0.5688	Remote Similarity	NPC475590
0.5676	Remote Similarity	NPC117445
0.5676	Remote Similarity	NPC308262
0.5657	Remote Similarity	NPC480914
0.5652	Remote Similarity	NPC119855
0.5577	Remote Similarity	NPC40749
0.5566	Remote Similarity	NPC208193
0.5545	Remote Similarity	NPC486136
0.5524	Remote Similarity	NPC240070
0.5505	Remote Similarity	NPC479357
0.5437	Remote Similarity	NPC480907
0.5429	Remote Similarity	NPC32177
0.5429	Remote Similarity	NPC469756
0.5429	Remote Similarity	NPC275901
0.5377	Remote Similarity	NPC188234
0.5347	Remote Similarity	NPC76572
0.5347	Remote Similarity	NPC193382
0.5327	Remote Similarity	NPC475629
0.5321	Remote Similarity	NPC146857
0.5321	Remote Similarity	NPC247190
0.5278	Remote Similarity	NPC125077
0.5248	Remote Similarity	NPC99080
0.5234	Remote Similarity	NPC480910
0.5234	Remote Similarity	NPC480909
0.52	Remote Similarity	NPC471633
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
0.5192	Remote Similarity	NPC193893
0.5185	Remote Similarity	NPC486127
0.5149	Remote Similarity	NPC84987
0.5143	Remote Similarity	NPC72260
0.5098	Remote Similarity	NPC479356
0.5098	Remote Similarity	NPC469750
0.5098	Remote Similarity	NPC479355
0.5093	Remote Similarity	NPC486130
0.5049	Remote Similarity	NPC199428
0.5049	Remote Similarity	NPC109448
0.5049	Remote Similarity	NPC310341

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488937 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6470
0.1-0.2	2581
0.2-0.3	79
0.3-0.4	8
0.4-0.5	9
0.5-0.6	1
0.6-0.7	1
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
0.6735	Remote Similarity	NPD8033	Approved
0.5143	Remote Similarity	NPD8294	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