NPASS Compound

Natural Product: NPC108721

Natural Product ID	NPC108721
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Polypodin
IUPAC Name	(2S,3R,5S,9R,10R,13R,14S,17S)-2,3,5,14-tetrahydroxy-10,13-dimethyl-17-[(2R,3R)-2,3,6-trihydroxy-6-methylheptan-2-yl]-1,2,3,4,9,11,12,15,16,17-decahydrocyclopenta[a]phenanthren-6-one
Synonyms	Polypodin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL502028
PubChem CID	441833
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001445] Bile acids, alcohols and derivatives [CHEMONTID:0002194] Hydroxy bile acids, alcohols 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 79 82 0 0 0 0 0 0 0 0999 V2000 -7.0253 -1.2091 1.3528 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3965 0.0476 1.2594 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9142 -0.0311 1.4708 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1365 -0.5010 0.2529 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8422 -1.9955 0.3950 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8978 0.3198 0.1377 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0800 0.2789 1.4208 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7239 0.9097 1.1356 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0177 -0.0552 0.2778 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6753 0.1177 -1.0917 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1158 -0.0272 -1.0433 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7293 -0.4508 -2.1269 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1785 -0.5957 -2.2217 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7819 -0.9004 -3.2608 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9813 -0.3604 -0.9841 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.6760 0.9583 -0.9526 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8076 0.8324 0.0593 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.8762 0.2503 -0.6262 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9693 -1.3821 -1.0247 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2838 1.3990 -1.5308 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1110 -0.8619 -1.8746 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5425 -0.4834 -1.4256 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3875 0.3502 -0.1617 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5085 0.1127 0.7275 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7791 0.6704 0.0572 C 0 0 1 0 0 0 0 0 0 0 0 0 4.9749 0.5826 0.8944 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2351 1.1453 0.3423 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8142 0.6445 -0.9075 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0595 0.7895 -2.0388 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2572 -0.8135 -0.8214 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1094 1.4577 -1.1395 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9636 -0.0736 -1.1361 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7726 -1.2581 0.8647 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3631 0.6114 2.1429 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1163 -1.4909 0.6308 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9848 -1.0435 1.2163 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7886 0.5928 2.1788 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5810 1.0018 1.7732 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7200 -0.7599 2.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3730 -2.1986 1.3648 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2823 -2.3741 -0.4764 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8131 -2.5448 0.3963 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1740 1.4089 0.0197 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5806 0.9156 2.1640 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0014 -0.7468 1.7725 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9752 1.8315 0.5256 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2438 1.2850 2.0254 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1340 -0.7150 -3.0202 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0461 1.7915 -0.6118 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0936 1.2611 -1.9360 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0791 1.8820 0.3527 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4171 0.9919 -0.9942 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4963 -1.3198 -1.8396 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0726 1.3685 -2.4982 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1273 -1.9070 -1.6288 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0759 -0.6970 -2.9666 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0415 0.0703 -2.2465 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0964 -1.4237 -1.2559 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3268 1.4143 -0.5007 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6201 1.7170 -0.2776 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8646 1.0583 1.9072 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1826 -0.5275 1.0576 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0744 1.0880 1.1224 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1480 2.2762 0.2251 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2463 0.0409 -2.6852 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3222 -1.2361 -1.8465 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3020 -0.8412 -0.4146 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6105 -1.4145 -0.1730 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5383 1.6973 -0.1553 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8175 0.8865 -1.7710 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7800 2.4073 -1.6023 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3642 -0.9561 -0.8808 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3418 -1.4005 1.6645 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1475 1.6705 2.2481 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5690 -0.0620 2.5956 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2675 0.2666 2.7039 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0157 -1.9672 0.1914 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1624 -1.6941 1.7188 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7372 -2.0825 0.2038 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 1 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 15 19 1 1 10 20 1 6 10 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 1 0 27 28 1 0 28 29 1 0 28 30 1 0 28 31 1 0 25 32 1 0 24 33 1 1 24 34 1 0 9 35 1 1 17 2 1 0 15 4 1 0 11 6 1 0 23 9 1 0 1 36 1 0 2 37 1 1 3 38 1 0 3 39 1 0 5 40 1 0 5 41 1 0 5 42 1 0 6 43 1 6 7 44 1 0 7 45 1 0 8 46 1 0 8 47 1 0 12 48 1 0 16 49 1 0 16 50 1 0 17 51 1 1 18 52 1 0 19 53 1 0 20 54 1 0 21 55 1 0 21 56 1 0 22 57 1 0 22 58 1 0 23 59 1 6 25 60 1 6 26 61 1 0 26 62 1 0 27 63 1 0 27 64 1 0 29 65 1 0 30 66 1 0 30 67 1 0 30 68 1 0 31 69 1 0 31 70 1 0 31 71 1 0 32 72 1 0 33 73 1 0 34 74 1 0 34 75 1 0 34 76 1 0 35 77 1 0 35 78 1 0 35 79 1 0 M END

Standard InCHIKey	GMFLGNRCCFYOKL-ACCCYTKYSA-N
Standard InCHI	InChI=1S/C27H44O8/c1-22(2,32)9-8-20(30)25(5,33)19-7-11-26(34)16-12-21(31)27(35)14-18(29)17(28)13-24(27,4)15(16)6-10-23(19,26)3/h12,15,17-20,28-30,32-35H,6-11,13-14H2,1-5H3/t15-,17-,18+,19-,20+,23+,24+,25+,26+,27+/m0/s1
SMILES	O[C@H]1C[C@]2(C)[C@H]3CC[C@]4([C@@](C3=CC(=O)[C@@]2(C[C@H]1O)O)(O)CC[C@@H]4[C@]([C@@H](CCC(O)(C)C)O)(O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	496.3	Volume:	506.371 ? Van der Waals volume.
Dense:	0.98	LogP:	0.893 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.658 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.41 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	21.0
TPSA:	158.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.297	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.26	Fsp³:	0.889
MCE-18:	94.314 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.167	Fluc inhibitor:	0.004 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.008 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.334	Promiscuous compounds:	0.466

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.812	MDCK Permeability:	-4.677
Pgp-inhibitor:	0.0	Pgp-substrate:	0.919
PAMPA:	1.0 ? 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):	0.002
20% Bioavailability (F20%):	0.18	30% Bioavailability (F30%):	0.108
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.165	MRP1:	0.193
Plasma Protein Binding (PPB):	76.735%	Volume Distribution (VD):	0.268
Fu:	23.214% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.675
BSEP inhibitor:	0.122

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:	0.006
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.056
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.006 ? 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):

1.583

Half-life (T1/2):

3.81

ADMET: Toxicity

hERG Blockers:	0.054	hERG Blockers (10um):	0.2
Human Hepatotoxicity (H-HT):	0.764	Drug-induced Liver Injury (DILI):	0.004
AMES Toxicity:	0.267	Rat Oral Acute Toxicity:	0.21
Maximum Recommended Daily Dose:	0.906	Skin Sensitization:	0.811
Carcinogencity:	0.935	Eye Corrosion:	0.0
Eye Irritation:	0.061	Respiratory Toxicity:	0.464
Drug-induced Neurotoxicity:	0.013	Ototoxicity:	0.9
Hematotoxicity:	0.067	Drug-induced Nephrotoxicity:	0.811
Genotoxicity:	0.712	RPMI-8226 Immunitoxicity:	0.122
A549 Cytotoxicity:	0.058	Hek293 Cytotoxicity:	0.315
BCF:	0.442 ? 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:	3.176 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.856 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.781 ? 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
NPO8680	Polypodium niponicum	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0031-9422(00)80275-7]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	flowering whole plant	n.a.	n.a.	PMID[10425119]
NPO15077	Achyranthes bidentata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11430011]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15043410]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15730237]
NPO14524	Delisea pulchra	Species	Bonnemaisoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16933872]
NPO10008	Tinospora capillipes	Species	Menispermaceae	Eukaryota	n.a.	root	n.a.	PMID[17340259]
NPO11394	Dichroa febrifuga	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19467876]
NPO25734	Tinospora sagittata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28836430]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9748375]
NPO10008	Tinospora capillipes	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5546	Calycophyllum spruceanum	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12993	Polypodium vulgare	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15077	Achyranthes bidentata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8680	Polypodium niponicum	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11394	Dichroa febrifuga	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12937	Tithonia pedunculata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14123	Achyranthes fauriei	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14524	Delisea pulchra	Species	Bonnemaisoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14017	Bulbine abyssinica	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11394	Dichroa febrifuga	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12993	Polypodium vulgare	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10008	Tinospora capillipes	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14123	Achyranthes fauriei	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15077	Achyranthes bidentata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8680	Polypodium niponicum	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10008	Tinospora capillipes	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25734	Tinospora sagittata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12993	Polypodium vulgare	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8680	Polypodium niponicum	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11394	Dichroa febrifuga	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15077	Achyranthes bidentata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14123	Achyranthes fauriei	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5546	Calycophyllum spruceanum	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15077	Achyranthes bidentata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12993	Polypodium vulgare	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8680	Polypodium niponicum	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10008	Tinospora capillipes	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO15077	Achyranthes bidentata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO23189	Achyranthes japonica	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO25734	Tinospora sagittata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14123	Achyranthes fauriei	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11394	Dichroa febrifuga	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8680	Polypodium niponicum	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3224	Chloridium virescens	Species	Chaetosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13240	Pinguipes brasilianus	Species	Pinguipedidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11394	Dichroa febrifuga	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15077	Achyranthes bidentata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8396	Quercus macrocarpa	Species	Fagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12993	Polypodium vulgare	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9459	Piper hoffmannseggianum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14017	Bulbine abyssinica	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14524	Delisea pulchra	Species	Bonnemaisoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO223	Rhaponticum carthamoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5546	Calycophyllum spruceanum	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5051	Lobelia urens	Species	Campanulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10008	Tinospora capillipes	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21864	Agathis alba	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25734	Tinospora sagittata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12937	Tithonia pedunculata	Species	Asteraceae	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
IC50	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT459	Individual protein	Human immunodeficiency virus type 1 reverse transcriptase	Human immunodeficiency virus 1	IC50	>	200.0	ug.mL-1	PMID[1710653]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC108721 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	19634
0.1-0.2	28098
0.2-0.3	2061
0.3-0.4	19
0.4-0.5	20
0.5-0.6	17
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC73300
0.7344	Intermediate Similarity	NPC222688
0.6562	Remote Similarity	NPC50692
0.6562	Remote Similarity	NPC260268
0.6562	Remote Similarity	NPC152695
0.6562	Remote Similarity	NPC319077
0.6562	Remote Similarity	NPC97202
0.6562	Remote Similarity	NPC601752
0.6154	Remote Similarity	NPC610677
0.5909	Remote Similarity	NPC600374
0.5833	Remote Similarity	NPC603506
0.5821	Remote Similarity	NPC48733
0.5821	Remote Similarity	NPC171137
0.5735	Remote Similarity	NPC296945
0.5588	Remote Similarity	NPC214264
0.5588	Remote Similarity	NPC85829
0.5571	Remote Similarity	NPC202167
0.5571	Remote Similarity	NPC49958
0.5556	Remote Similarity	NPC250109
0.5362	Remote Similarity	NPC475060
0.5362	Remote Similarity	NPC83744
0.5286	Remote Similarity	NPC220229
0.5286	Remote Similarity	NPC601682
0.527	Remote Similarity	NPC600136
0.5217	Remote Similarity	NPC11710
0.5068	Remote Similarity	NPC476027

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC108721 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7027
0.1-0.2	2000
0.2-0.3	123
0.3-0.4	0
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