NPASS Compound

Natural Product: NPC67056

Natural Product ID	NPC67056
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Echinulin
IUPAC Name	(3S,6S)-3-methyl-6-[[2-(2-methylbut-3-en-2-yl)-5,7-bis(3-methylbut-2-enyl)-1H-indol-3-yl]methyl]piperazine-2,5-dione
Synonyms	Echinulin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL251450
PubChem CID	115252
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids 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 73 75 0 0 0 0 0 0 0 0999 V2000 1.5289 -3.8614 0.0875 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6198 -3.4075 -1.1561 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0921 -1.9759 -1.3116 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0226 -1.0850 -0.8866 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2104 -1.5503 -0.5128 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.0361 -0.5425 -0.2376 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3879 0.6584 -0.4155 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9076 0.2852 -0.8223 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9607 1.2687 -1.0414 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6890 1.7646 0.1827 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6924 2.6861 -0.2933 N 0 0 0 0 0 0 0 0 0 0 0 0 4.9138 2.5814 0.0229 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8716 3.5095 -0.4673 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4007 1.5189 0.8947 C 0 0 1 0 0 0 0 0 0 0 0 0 4.4174 0.6647 1.4665 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1534 0.7773 1.1368 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2824 -0.1114 1.7641 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4831 0.7028 0.2005 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9847 1.8807 -0.2068 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2971 1.9410 0.2019 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9708 0.7540 0.3883 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3547 -0.4617 0.1735 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1355 -1.7007 0.3960 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7732 -2.3591 1.6633 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3906 -3.5998 1.8367 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2636 -4.5740 0.7145 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0646 -4.0617 3.2321 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9431 3.2342 0.4262 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6295 3.7500 -0.7981 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9222 3.9753 -0.7499 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6349 4.4865 -1.9429 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6804 3.7254 0.4886 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4016 -1.9281 -0.6497 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3605 -1.8524 -2.8244 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7701 -3.2702 0.9620 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1963 -4.8832 0.2950 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3648 -4.0482 -1.9629 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5198 -2.5585 -0.4370 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5445 2.1678 -1.5579 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7894 0.8333 -1.6779 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9809 2.4584 0.7699 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6100 4.0388 -1.3057 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9456 2.0536 1.7434 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5931 -0.8373 2.3945 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9326 0.0280 0.9316 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0540 0.1909 -0.6745 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2229 1.4740 -0.1668 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4200 2.7786 -0.3644 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0211 0.7495 0.7146 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2306 -1.4954 0.4157 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0081 -2.4125 -0.4644 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8419 -1.7028 2.5576 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0156 -4.3690 -0.0621 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5309 -5.5870 1.1461 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2413 -4.6668 0.3276 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1604 -5.1554 3.2669 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0028 -3.7826 3.4525 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7060 -3.5724 3.9825 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2065 4.0306 0.7061 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6459 3.1586 1.2767 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0364 3.9281 -1.7072 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7352 3.7189 -2.7381 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6858 4.7924 -1.6807 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0896 5.3323 -2.3954 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3018 4.3193 1.3563 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7789 3.9099 0.3363 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5410 2.6554 0.7654 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0006 -2.7859 -1.1040 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4190 -2.1947 0.4326 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0305 -1.0518 -0.9062 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7869 -2.6077 -3.3982 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4239 -1.8643 -3.0603 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9363 -0.8658 -3.1298 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 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 12 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 14 18 1 0 7 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 2 3 25 26 1 0 25 27 1 0 20 28 1 0 28 29 1 0 29 30 2 3 30 31 1 0 30 32 1 0 3 33 1 0 3 34 1 0 8 4 2 0 16 10 1 0 22 6 1 0 1 35 1 0 1 36 1 0 2 37 1 0 5 38 1 0 9 39 1 0 9 40 1 0 10 41 1 1 13 42 1 0 14 43 1 1 17 44 1 0 18 45 1 0 18 46 1 0 18 47 1 0 19 48 1 0 21 49 1 0 23 50 1 0 23 51 1 0 24 52 1 0 26 53 1 0 26 54 1 0 26 55 1 0 27 56 1 0 27 57 1 0 27 58 1 0 28 59 1 0 28 60 1 0 29 61 1 0 31 62 1 0 31 63 1 0 31 64 1 0 32 65 1 0 32 66 1 0 32 67 1 0 33 68 1 0 33 69 1 0 33 70 1 0 34 71 1 0 34 72 1 0 34 73 1 0 M END

Standard InCHIKey	DIKMWTRJIZQJMY-CYFREDJKSA-N
Standard InCHI	InChI=1S/C29H39N3O2/c1-9-29(7,8)26-23(16-24-28(34)30-19(6)27(33)31-24)22-15-20(12-10-17(2)3)14-21(25(22)32-26)13-11-18(4)5/h9-11,14-15,19,24,32H,1,12-13,16H2,2-8H3,(H,30,34)(H,31,33)/t19-,24-/m0/s1
SMILES	C=CC(c1[nH]c2c(c1C[C@@H]1N=C(O)[C@@H](N=C1O)C)cc(cc2CC=C(C)C)CC=C(C)C)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	461.3	Volume:	511.313 ? Van der Waals volume.
Dense:	0.902	LogP:	5.342 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.762 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.352 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	19.0
TPSA:	80.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.375	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.639	Fsp³:	0.448
MCE-18:	74.286 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.959	Fluc inhibitor:	0.058 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.727 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.787 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.011	Promiscuous compounds:	0.354

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.761	MDCK Permeability:	-4.656
Pgp-inhibitor:	0.66	Pgp-substrate:	0.836
PAMPA:	0.321 ? 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):	0.142
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.98
Plasma Protein Binding (PPB):	86.758%	Volume Distribution (VD):	0.441
Fu:	12.996% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.991
OATP1B3 inhibitor:	0.984	BCRP inhibitor:	1.0
BSEP inhibitor:	0.762

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.159	CYP2D6-substrate:	0.009
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.998
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

2.871

Half-life (T1/2):

1.389

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.071
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	0.996
AMES Toxicity:	0.164	Rat Oral Acute Toxicity:	0.934
Maximum Recommended Daily Dose:	0.698	Skin Sensitization:	1.0
Carcinogencity:	0.263	Eye Corrosion:	0.0
Eye Irritation:	0.043	Respiratory Toxicity:	0.956
Drug-induced Neurotoxicity:	0.667	Ototoxicity:	0.979
Hematotoxicity:	0.513	Drug-induced Nephrotoxicity:	0.978
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.005
A549 Cytotoxicity:	0.006	Hek293 Cytotoxicity:	0.057
BCF:	2.159 ? 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:	5.029 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.776 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.349 ? 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
NPO31540	Aspergillus variecolor	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/jo00010a040]
NPO24419	Anvillea garcinii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11087618]
NPO31540	Aspergillus variecolor	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17896816]
NPO31540	Aspergillus variecolor	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17965475]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19948405]
NPO32843	eurotium cristatum en-220	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22727636]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	Eukaryota	n.a.	seed	n.a.	PMID[23672042]
NPO32640	eurotium rubrum ma-150	Species	Aspergillaceae	Eukaryota	Fungus Obtained from Marine Mangrove-Derived Rhizospheric Soil.	n.a.	n.a.	PMID[25730346]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36483735]
NPO24419	Anvillea garcinii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8699183]
NPO5568	Neobulgaria pura	Species	Leotiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11271	Plantago subspathulata	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17300	Noccaea caerulescens	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24570	Cladonia japonica	Species	Cladoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25152	Telekia speciosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24419	Anvillea garcinii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31540	Aspergillus variecolor	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25152	Telekia speciosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25152	Telekia speciosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5568	Neobulgaria pura	Species	Leotiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17300	Noccaea caerulescens	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11271	Plantago subspathulata	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21269	Equisetum fluviatile	Species	Equisetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14759	Hymenaea parvifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24570	Cladonia japonica	Species	Cladoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24419	Anvillea garcinii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12424	Streptococcus equinus	Species	Streptococcaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO25152	Telekia speciosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28574	Oroxylum indicum	Species	Bignoniaceae	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	5
Inhibition	2
IZ	1
MIC	1
CC50	1

Activity Type	# Activity
Individual protein	6
Cell line	1
Organism	2
Others	1
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT270	Individual protein	Nitric oxide synthase, inducible	Mus musculus	IC50	>	50000.0	nM	PMID[18926710]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	Activity	<	40.0	%	PMID[21667972]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Activity	<	40.0	%	PMID[21667972]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	Activity	<	40.0	%	PMID[21667972]
NPT232	Individual protein	Cannabinoid CB1 receptor	Homo sapiens	Activity	<	40.0	%	PMID[21667972]
NPT1287	Individual protein	Cannabinoid CB2 receptor	Homo sapiens	Activity	<	40.0	%	PMID[21667972]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT616	Cell line	MDCK	Canis lupus familiaris	CC50	>	200000.0	nM	PMID[25681711]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	12.99	%	PMID[25681711]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	169.9	ug.mL-1	PMID[28628823]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	8.0	mm	PMID[22727636]
NPT2	Others	Unspecified	n.a.	Inhibition	=	8.8	%	PMID[18926710]

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 NPC67056 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	33357
0.1-0.2	16076
0.2-0.3	395
0.3-0.4	20
0.4-0.5	4
0.5-0.6	1
0.6-0.7	2
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	Natural Product ID
0.8154	Intermediate Similarity	NPC470508
0.7385	Intermediate Similarity	NPC16667
0.625	Remote Similarity	NPC472586
0.6111	Remote Similarity	NPC280548
0.5882	Remote Similarity	NPC285469

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC67056 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5137
0.1-0.2	3963
0.2-0.3	49
0.3-0.4	1
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