NPASS Compound

Natural Product: NPC158662

Natural Product ID	NPC158662
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Primulagenin
IUPAC Name	(3S,4aR,6aR,6bS,8R,8aS,12aS,14aR,14bR)-8a-(hydroxymethyl)-4,4,6a,6b,11,11,14b-heptamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicene-3,8-diol
Synonyms	Primulagenin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL496854
PubChem CID	10004345
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 83 87 0 0 0 0 0 0 0 0999 V2000 -4.8579 -3.0120 -0.7082 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7593 -1.7003 0.0919 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6159 -1.9760 1.3339 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3193 -0.6161 -0.7683 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2231 0.2953 -1.2564 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5222 0.9306 -0.0810 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6225 1.5997 0.7645 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0017 2.2194 1.8830 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8992 -0.1151 0.7502 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3212 -1.5329 0.4378 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3888 -0.1430 0.6824 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7994 -0.8770 1.6190 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6605 -1.0574 1.7569 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3942 -0.3483 0.6746 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8848 -0.2257 0.9037 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2342 0.6487 2.0722 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5038 -1.5627 1.1562 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0163 -2.2376 -0.0878 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0889 -1.4329 -0.7858 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8683 0.0521 -0.6501 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1705 0.6731 -2.0244 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7983 0.7027 0.3198 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4205 0.2794 -0.4101 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9682 1.6840 -0.6330 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4998 1.8543 -0.5594 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7358 0.9461 0.3215 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3599 1.7458 1.5777 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6024 0.5699 -0.3312 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3400 -0.4505 -1.4516 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2762 1.7340 -0.9581 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6309 2.0624 -0.4911 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3115 2.7150 -1.5534 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3737 -1.7989 -0.3395 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1635 -3.0007 -1.5720 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6124 -3.8253 0.0040 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9266 -3.0831 -1.0113 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5572 -3.0437 1.6173 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3160 -1.3136 2.1758 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6527 -1.7123 1.0568 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7720 -1.0441 -1.7216 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1788 -0.0851 -0.3083 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5224 -0.3348 -1.8501 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6639 1.0989 -1.9018 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3133 0.8845 1.2075 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1006 2.4293 0.2044 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3164 3.1270 2.0205 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1270 0.0464 1.8413 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1132 -2.1468 1.3463 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7119 -1.9735 -0.3780 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4054 -1.4114 2.3735 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9388 -0.8106 2.7790 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8266 -2.1717 1.6518 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3231 -1.0018 -0.2473 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5659 0.4007 2.9258 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2582 0.3478 2.4475 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2749 1.7119 1.8772 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8528 -2.2922 1.6764 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4023 -1.4545 1.8347 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1988 -2.5400 -0.7746 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5053 -3.1858 0.2439 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0476 -1.7276 -1.8554 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1294 0.2706 -2.3895 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3227 0.4969 -2.7247 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3193 1.7538 -1.8304 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7396 1.0194 -0.2224 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3965 1.6136 0.7610 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1845 -0.0367 1.0781 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8968 -0.3352 -1.2081 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2871 1.9532 -1.6860 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5419 2.4264 -0.0077 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0495 1.7902 -1.5941 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3270 2.9397 -0.2836 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0642 2.6229 1.6922 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3317 1.1313 2.4769 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6412 2.2111 1.4753 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4559 -1.4822 -1.1050 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1528 -0.3104 -2.2244 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5993 -0.2336 -1.9882 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2648 1.6818 -2.0884 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6269 2.6379 -0.7523 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6277 2.8266 0.3159 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6760 3.2555 -2.0928 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0286 -1.7473 -1.0915 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 1 7 8 1 0 6 9 1 0 9 10 1 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 1 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 20 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 1 26 28 1 0 28 29 1 6 28 30 1 0 30 31 1 0 31 32 1 0 19 33 1 0 10 2 1 0 28 11 1 0 31 6 1 0 26 14 1 0 23 15 1 0 1 34 1 0 1 35 1 0 1 36 1 0 3 37 1 0 3 38 1 0 3 39 1 0 4 40 1 0 4 41 1 0 5 42 1 0 5 43 1 0 7 44 1 0 7 45 1 0 8 46 1 0 9 47 1 1 10 48 1 0 10 49 1 0 12 50 1 0 13 51 1 0 13 52 1 0 14 53 1 6 16 54 1 0 16 55 1 0 16 56 1 0 17 57 1 0 17 58 1 0 18 59 1 0 18 60 1 0 19 61 1 6 21 62 1 0 21 63 1 0 21 64 1 0 22 65 1 0 22 66 1 0 22 67 1 0 23 68 1 6 24 69 1 0 24 70 1 0 25 71 1 0 25 72 1 0 27 73 1 0 27 74 1 0 27 75 1 0 29 76 1 0 29 77 1 0 29 78 1 0 30 79 1 0 30 80 1 0 31 81 1 1 32 82 1 0 33 83 1 0 M END

Standard InCHIKey	YHGVYECWZWIVJC-TVZJSHMMSA-N
Standard InCHI	InChI=1S/C30H50O3/c1-25(2)14-15-30(18-31)20(16-25)19-8-9-22-27(5)12-11-23(32)26(3,4)21(27)10-13-28(22,6)29(19,7)17-24(30)33/h8,20-24,31-33H,9-18H2,1-7H3/t20-,21-,22+,23-,24+,27-,28+,29+,30+/m0/s1
SMILES	CC1(C)CC[C@@]2(CO)[C@@H](C1)C1=CC[C@@H]3[C@@]4(C)CC[C@@H](C(C)(C)[C@@H]4CC[C@@]3(C)[C@]1(C)C[C@H]2O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	458.38	Volume:	508.388 ? Van der Waals volume.
Dense:	0.902	LogP:	4.156 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.949 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.977 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	26.0
TPSA:	60.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	3.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.415	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.889	Fsp³:	0.933
MCE-18:	104.897 ? 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:	0.659	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? 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:	0.446	Promiscuous compounds:	0.086

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.297	MDCK Permeability:	-4.925
Pgp-inhibitor:	0.003	Pgp-substrate:	0.212
PAMPA:	0.991 ? 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%):	0.992	30% Bioavailability (F30%):	0.688
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	1.0	MRP1:	0.746
Plasma Protein Binding (PPB):	94.28%	Volume Distribution (VD):	-0.245
Fu:	6.051% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.025	BCRP inhibitor:	0.869
BSEP inhibitor:	0.719

ADMET: Metabolism

CYP1A2-inhibitor:	0.004	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.764	CYP2C19-substrate:	0.93
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.005
CYP3A4-inhibitor:	0.053	CYP3A4-substrate:	0.192
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.934
HLM stability:	0.506 ? 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):

8.848

Half-life (T1/2):

0.626

ADMET: Toxicity

hERG Blockers:	0.04	hERG Blockers (10um):	0.212
Human Hepatotoxicity (H-HT):	0.596	Drug-induced Liver Injury (DILI):	0.249
AMES Toxicity:	0.622	Rat Oral Acute Toxicity:	0.721
Maximum Recommended Daily Dose:	0.611	Skin Sensitization:	0.993
Carcinogencity:	0.968	Eye Corrosion:	0.007
Eye Irritation:	0.403	Respiratory Toxicity:	0.946
Drug-induced Neurotoxicity:	0.2	Ototoxicity:	0.515
Hematotoxicity:	0.705	Drug-induced Nephrotoxicity:	0.849
Genotoxicity:	0.746	RPMI-8226 Immunitoxicity:	0.089
A549 Cytotoxicity:	0.905	Hek293 Cytotoxicity:	0.719
BCF:	2.065 ? 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:	4.051 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.41 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.801 ? 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
NPO1872	Picramnia latifolia	Species	Picramniaceae	Eukaryota	n.a.	Peru	n.a.	PMID[15043409]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	n.a.	leaf	n.a.	PMID[16926516]
NPO21278	Lysimachia clethroides	Species	Primulaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21928797]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	flower buds	n.a.	n.a.	PMID[22834923]
NPO24324	Halobacterium salinarum	Species	Halobacteriaceae	Archaea	n.a.	n.a.	n.a.	PMID[24823651]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	root	n.a.	n.a.	PMID[2778455]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29300477]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	Roots	n.a.	n.a.	PMID[30395460]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32569471]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39065796]
NPO3720	Primula obconica	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	fruit	n.a.	Database[Article]
NPO807	Lasiolaena morii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21278	Lysimachia clethroides	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21437	Rhododendron aureum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23859	Primula elatior	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1872	Picramnia latifolia	Species	Picramniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11826	Arctotis revoluta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20080	Lepisorus thunbergianus	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3720	Primula obconica	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23859	Primula elatior	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21935	Exallage auricularia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20080	Lepisorus thunbergianus	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21437	Rhododendron aureum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23859	Primula elatior	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10403	Ficus nitida	Species	Ficidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3720	Primula obconica	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21278	Lysimachia clethroides	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21437	Rhododendron aureum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24324	Halobacterium salinarum	Species	Halobacteriaceae	Archaea	n.a.	n.a.	n.a.	Database[UNPD]
NPO21278	Lysimachia clethroides	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10581	Allium erubescens	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20080	Lepisorus thunbergianus	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23380	Camellia japonica	Species	Theaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23859	Primula elatior	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10403	Ficus nitida	Species	Ficidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO807	Lasiolaena morii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1872	Picramnia latifolia	Species	Picramniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11826	Arctotis revoluta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21935	Exallage auricularia	Species	Rubiaceae	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	1

Activity Type	# Activity
Individual protein	1
Cell line	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
NPT804	Cell line	HT-22	Mus musculus	Activity	=	60.5	%	PMID[32569471]

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 NPC158662 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	26425
0.1-0.2	19482
0.2-0.3	2794
0.3-0.4	898
0.4-0.5	171
0.5-0.6	59
0.6-0.7	12
0.7-0.8	0
0.8-0.85	2
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	NPC253807
0.8	Intermediate Similarity	NPC311078
0.8	Intermediate Similarity	NPC34177
0.7679	Intermediate Similarity	NPC101475
0.7455	Intermediate Similarity	NPC290598
0.7455	Intermediate Similarity	NPC30590
0.7241	Intermediate Similarity	NPC235341
0.7241	Intermediate Similarity	NPC480924
0.7119	Intermediate Similarity	NPC159168
0.7097	Intermediate Similarity	NPC488519
0.678	Remote Similarity	NPC196753
0.6613	Remote Similarity	NPC246708
0.661	Remote Similarity	NPC474989
0.6377	Remote Similarity	NPC86368
0.629	Remote Similarity	NPC238992
0.619	Remote Similarity	NPC480950
0.6176	Remote Similarity	NPC294360
0.6032	Remote Similarity	NPC230295
0.6032	Remote Similarity	NPC253402
0.6032	Remote Similarity	NPC53744
0.6032	Remote Similarity	NPC470588
0.6032	Remote Similarity	NPC98386
0.5968	Remote Similarity	NPC132478
0.5915	Remote Similarity	NPC283343
0.5882	Remote Similarity	NPC164349
0.5833	Remote Similarity	NPC473160
0.5738	Remote Similarity	NPC27765
0.5738	Remote Similarity	NPC122418
0.5738	Remote Similarity	NPC491014
0.5714	Remote Similarity	NPC237344
0.5672	Remote Similarity	NPC480946
0.5672	Remote Similarity	NPC130577
0.5672	Remote Similarity	NPC142415
0.5672	Remote Similarity	NPC102683
0.5652	Remote Similarity	NPC228784
0.5652	Remote Similarity	NPC324341
0.5652	Remote Similarity	NPC601810
0.5625	Remote Similarity	NPC40394
0.5625	Remote Similarity	NPC478657
0.5571	Remote Similarity	NPC480919
0.5526	Remote Similarity	NPC167383
0.5484	Remote Similarity	NPC120098
0.5479	Remote Similarity	NPC471433
0.5479	Remote Similarity	NPC471432
0.5441	Remote Similarity	NPC213412
0.5441	Remote Similarity	NPC198664
0.5441	Remote Similarity	NPC2539
0.5362	Remote Similarity	NPC7260
0.5362	Remote Similarity	NPC182797
0.5362	Remote Similarity	NPC210037
0.5362	Remote Similarity	NPC120968
0.5362	Remote Similarity	NPC171203
0.5362	Remote Similarity	NPC307426
0.5362	Remote Similarity	NPC98442
0.5362	Remote Similarity	NPC242468
0.5362	Remote Similarity	NPC227467
0.5362	Remote Similarity	NPC273621
0.5362	Remote Similarity	NPC52169
0.5362	Remote Similarity	NPC488562
0.5303	Remote Similarity	NPC95594
0.5238	Remote Similarity	NPC601696
0.5217	Remote Similarity	NPC187722
0.5217	Remote Similarity	NPC136313
0.5211	Remote Similarity	NPC202728
0.5211	Remote Similarity	NPC158059
0.5211	Remote Similarity	NPC49776
0.5211	Remote Similarity	NPC63118
0.5211	Remote Similarity	NPC474436
0.5205	Remote Similarity	NPC488520
0.52	Remote Similarity	NPC258547
0.5152	Remote Similarity	NPC291379
0.5152	Remote Similarity	NPC475862
0.5143	Remote Similarity	NPC51700
0.5143	Remote Similarity	NPC88716
0.5143	Remote Similarity	NPC68160
0.5143	Remote Similarity	NPC112866
0.5132	Remote Similarity	NPC480920
0.5075	Remote Similarity	NPC3915
0.5072	Remote Similarity	NPC477872
0.5067	Remote Similarity	NPC273668
0.5067	Remote Similarity	NPC488522

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC158662 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8051
0.1-0.2	1063
0.2-0.3	31
0.3-0.4	4
0.4-0.5	0
0.5-0.6	1
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
0.5588	Remote Similarity	NPD7645	Phase 2

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