NPASS Compound

Natural Product: NPC234335

Natural Product ID	NPC234335
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	24-Methylcholesta-5,24(28)-Diene-3Beta,19-Diol-7Beta-Mono Aetate
IUPAC Name	[(3S,7R,8S,9S,10S,13R,14S,17R)-3-hydroxy-10-(hydroxymethyl)-13-methyl-17-[(2R)-6-methyl-5-methylideneheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-7-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL471810
PubChem CID	12069909
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003567] Ergostane steroids [CHEMONTID:0001403] Ergosterols 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 82 85 0 0 0 0 0 0 0 0999 V2000 -2.3878 1.9742 -3.1199 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2493 1.9265 -2.0708 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5139 0.5511 -1.4900 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0825 -0.2900 -2.6452 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2756 0.3548 -3.2348 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3844 0.3760 -2.2064 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.9771 1.0216 -0.9265 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6236 0.6061 -0.5055 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4151 0.3084 0.7382 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1761 -0.1095 1.4190 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0236 0.0039 0.5037 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3051 -0.1042 -0.9735 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0283 0.2998 -1.6757 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1737 -0.4822 -1.2838 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3950 -0.5283 0.2241 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9642 -1.0243 0.7315 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7020 -1.4976 2.0934 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5534 -2.3569 1.8199 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2313 -1.6637 0.6566 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6561 -1.4634 1.0059 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5058 -0.9188 -0.1077 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9280 -0.7774 0.3797 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8251 -0.2523 -0.6866 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3551 0.0191 -1.8806 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2641 -0.0342 -0.3976 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0255 0.4547 -1.5878 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4575 0.9638 0.7273 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8739 -0.8086 2.3389 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6433 0.7975 0.8254 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9175 0.7767 2.5332 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9228 0.3856 3.8364 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1646 -0.8032 4.1282 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6328 1.4195 4.8809 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5174 1.0243 -2.6844 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7106 1.6489 -3.9735 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1740 2.4685 -2.3495 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7984 2.5990 -1.2705 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2894 -0.5511 -3.3686 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4072 -1.2554 -2.1893 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6564 -0.3310 -4.0476 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1602 1.3384 -3.6778 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6728 -0.6751 -1.9938 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1030 2.1272 -0.9299 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7457 0.6871 -0.1614 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2996 0.3730 1.4131 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3036 -1.1062 1.9157 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6066 1.0538 0.6267 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4029 -1.2142 -1.1790 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7863 1.3586 -1.6059 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1766 0.0723 -2.7745 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0795 -1.5449 -1.6208 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0421 -0.0626 -1.8131 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1785 -1.9356 0.0981 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5064 -2.1593 2.4564 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 -0.7366 2.8475 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1660 -2.4973 2.7008 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1582 -3.3652 1.5451 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2179 -2.4164 -0.1914 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0547 -2.5248 1.1378 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5380 -1.6660 -0.9379 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1181 0.0098 -0.5508 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0498 -0.0972 1.2334 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3251 -1.8038 0.6104 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0164 0.4040 -2.6594 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3206 -0.1119 -2.1772 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7673 -0.9787 -0.0549 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5861 1.4509 -1.8849 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0779 0.6092 -1.2794 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9536 -0.2101 -2.4655 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2736 0.4896 1.6922 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8518 1.8682 0.5446 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5180 1.2859 0.6968 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9050 -0.6189 2.8804 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4071 0.1395 2.3281 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4452 -1.4583 3.0676 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6720 1.0847 1.0192 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2743 1.5909 0.1072 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0775 0.9845 1.7681 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3826 1.2718 5.6903 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5888 1.3304 5.2399 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7607 2.4373 4.4651 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3202 0.4880 -2.5716 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 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 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 25 27 1 0 20 28 1 0 15 29 1 1 10 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 6 34 1 0 8 3 1 0 16 11 1 0 12 3 1 0 19 15 1 0 1 35 1 0 2 36 1 0 2 37 1 0 4 38 1 0 4 39 1 0 5 40 1 0 5 41 1 0 6 42 1 1 7 43 1 0 7 44 1 0 9 45 1 0 10 46 1 1 11 47 1 6 12 48 1 1 13 49 1 0 13 50 1 0 14 51 1 0 14 52 1 0 16 53 1 6 17 54 1 0 17 55 1 0 18 56 1 0 18 57 1 0 19 58 1 6 20 59 1 1 21 60 1 0 21 61 1 0 22 62 1 0 22 63 1 0 24 64 1 0 24 65 1 0 25 66 1 0 26 67 1 0 26 68 1 0 26 69 1 0 27 70 1 0 27 71 1 0 27 72 1 0 28 73 1 0 28 74 1 0 28 75 1 0 29 76 1 0 29 77 1 0 29 78 1 0 33 79 1 0 33 80 1 0 33 81 1 0 34 82 1 0 M END

Standard InCHIKey	DXVRFEYOLWHNIF-VGBUTIAVSA-N
Standard InCHI	InChI=1S/C30H48O4/c1-18(2)19(3)7-8-20(4)24-9-10-25-28-26(12-13-29(24,25)6)30(17-31)14-11-23(33)15-22(30)16-27(28)34-21(5)32/h16,18,20,23-28,31,33H,3,7-15,17H2,1-2,4-6H3/t20-,23+,24-,25+,26+,27+,28+,29-,30-/m1/s1
SMILES	OC[C@]12CC[C@@H](CC1=C[C@@H]([C@@H]1[C@@H]2CC[C@]2([C@H]1CC[C@@H]2[C@@H](CCC(=C)C(C)C)C)C)OC(=O)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	472.36	Volume:	520.462 ? Van der Waals volume.
Dense:	0.908	LogP:	4.432 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.05 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.901 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	22.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.349	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.868	Fsp³:	0.833
MCE-18:	73.818 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.885	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? 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:	0.23	Promiscuous compounds:	0.252

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.333	MDCK Permeability:	-5.025
Pgp-inhibitor:	0.819	Pgp-substrate:	0.091
PAMPA:	0.003 ? 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%):	0.144	30% Bioavailability (F30%):	0.945
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.276
Plasma Protein Binding (PPB):	86.307%	Volume Distribution (VD):	-0.332
Fu:	10.398% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.275
BSEP inhibitor:	0.794

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.006
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.55
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.92 ? 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):

8.591

Half-life (T1/2):

1.215

ADMET: Toxicity

hERG Blockers:	0.046	hERG Blockers (10um):	0.151
Human Hepatotoxicity (H-HT):	0.526	Drug-induced Liver Injury (DILI):	0.26
AMES Toxicity:	0.289	Rat Oral Acute Toxicity:	0.094
Maximum Recommended Daily Dose:	0.409	Skin Sensitization:	0.948
Carcinogencity:	0.653	Eye Corrosion:	0.012
Eye Irritation:	0.826	Respiratory Toxicity:	0.458
Drug-induced Neurotoxicity:	0.054	Ototoxicity:	0.655
Hematotoxicity:	0.422	Drug-induced Nephrotoxicity:	0.502
Genotoxicity:	0.128	RPMI-8226 Immunitoxicity:	0.047
A549 Cytotoxicity:	0.156	Hek293 Cytotoxicity:	0.162
BCF:	1.631 ? 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:	4.182 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.823 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.083 ? 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
NPO14781	Anthocleista vogelii	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0031-9422(00)97499-5]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[10843584]
NPO9675	Aphanoascus fulvescens	Species	Onygenaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10908107]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15497934]
NPO13916	Nephthea erecta	Species	Nephtheidae	Eukaryota	n.a.	formosan soft coral	n.a.	PMID[17845002]
NPO17094	Sinularia depressa	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[20121250]
NPO17094	Sinularia depressa	Species	Alcyoniidae	Eukaryota	n.a.	Hainan soft coral	n.a.	PMID[23357636]
NPO13916	Nephthea erecta	Species	Nephtheidae	Eukaryota	n.a.	Formosan soft coral	n.a.	PMID[24370010]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[30407007]
NPO13916	Nephthea erecta	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9722490]
NPO14781	Anthocleista vogelii	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17094	Sinularia depressa	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13916	Nephthea erecta	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9675	Aphanoascus fulvescens	Species	Onygenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24165	Litophyton arboreum	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6694	Picconia excelsa	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6931	Senna multiglandulosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14781	Anthocleista vogelii	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6694	Picconia excelsa	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24165	Litophyton arboreum	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13916	Nephthea erecta	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9675	Aphanoascus fulvescens	Species	Onygenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6931	Senna multiglandulosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17094	Sinularia depressa	Species	Alcyoniidae	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
ED50	4
MIC50	1

Activity Type	# Activity
Cell line	4
Organism	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
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.81	ug ml-1	PMID[9722490]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	0.87	ug ml-1	PMID[9722490]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.38	ug ml-1	PMID[9722490]
NPT168	Cell line	P388	Mus musculus	ED50	=	0.42	ug ml-1	PMID[9722490]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC50	=	1000000.0	nM	PMID[23357636]

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 NPC234335 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	15476
0.1-0.2	25808
0.2-0.3	8203
0.3-0.4	282
0.4-0.5	74
0.5-0.6	8
0.6-0.7	4
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
0.6613	Remote Similarity	NPC87604
0.6562	Remote Similarity	NPC186688
0.6349	Remote Similarity	NPC209620
0.6087	Remote Similarity	NPC218186
0.5781	Remote Similarity	NPC134847
0.5672	Remote Similarity	NPC26117
0.5556	Remote Similarity	NPC489072
0.5538	Remote Similarity	NPC84694
0.5538	Remote Similarity	NPC143182
0.5441	Remote Similarity	NPC474752
0.5441	Remote Similarity	NPC474683
0.507	Remote Similarity	NPC278648

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC234335 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5938
0.1-0.2	2977
0.2-0.3	220
0.3-0.4	12
0.4-0.5	3
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